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IBD Medications Show No Link with Breast Cancer Recurrence
, according to investigators.
These findings diminish concerns that IBD therapy could theoretically reactivate dormant micrometastases, lead author Guillaume Le Cosquer, MD, of Toulouse University Hospital, Toulouse, France, and colleagues, reported.
“In patients with IBD, medical management of subjects with a history of breast cancer is a frequent and unresolved problem for clinicians,” the investigators wrote in Clinical Gastroenterology and Hepatology (2024 Nov. doi: 10.1016/j.cgh.2024.09.034).
Previous studies have reported that conventional immunosuppressants and biologics do not increase risk of incident cancer among IBD patients with a prior nondigestive malignancy; however, recent guidelines from the European Crohn’s and Colitis Organisation (ECCO) suggest that data are insufficient to make associated recommendations, prompting the present study.
“[T]he major strength of our work is that it is the first to focus on the most frequent cancer (breast cancer) in patients with IBD only, with the longest follow-up after breast cancer in patients with IBD ever published,” Dr. Le Cosquer and colleagues noted.
The dataset included 207 patients with IBD and a history of breast cancer, drawn from 7 tertiary centers across France.
The index date was the time of breast cancer diagnosis, and patients were followed for a median of 71 months. The median time from cancer diagnosis to initiation of IBD treatment was 28 months.
First-line post-cancer treatments included conventional immunosuppressants (19.3%), anti–tumor necrosis factor (anti-TNF) agents (19.8%), vedolizumab (7.2%), and ustekinumab (1.9%). Approximately half (51.6%) received no immunosuppressive therapy during follow-up.
Over the study period, 42 incident cancers were recorded (20.3%), among which 34 were breast cancer recurrences. Adjusted incidence rates per 1000 person-years were 10.2 (95% CI, 6.0–16.4) in the untreated group and 28.9 (95% CI, 11.6–59.6) in patients exposed to immunosuppressive or biologic therapies (P = .0519). Incident cancer–free survival did not differ significantly between treated and untreated groups (P = .4796).
On multivariable analysis, independent predictors of incident cancer included T4d stage (P = .036), triple-negative status (P = .016), and follow-up duration shorter than 71 months (P = .005).
“[I]mmunosuppressant and biologic use in selected patients with IBD with prior breast cancer does not seem to increase the risk of incident cancer,” the investigators wrote, noting that the main predictors of cancer recurrence were known poor prognostic features of breast cancer.
Dr. Le Cosquer and colleagues acknowledged a lack of prospective safety data for biologic therapies among patients with prior malignancy, as these individuals are often excluded from clinical trials. Still, they underscored alignment between their findings and earlier retrospective studies, including analyses from the SAPPHIRE registry and Medicare data, which also found no significant increase in breast cancer recurrence with anti-TNF agents or newer biologics such as vedolizumab and ustekinumab.
“Our findings will help clinicians to make decisions in multidisciplinary meetings to start immunosuppressants or biologics in case of IBD flare-up in these patients,” they concluded.
The investigators disclosed relationships with AbbVie, Janssen, Takeda, and others.
Patients with inflammatory bowel disease (IBD) are at risk for a host of other illnesses, including cancer, at rates similar to or greater than the general population. When faced with uncertainty about drug safety with a cancer diagnosis, the reflex is to avoid the therapy altogether. This may lead to significant flares which may in turn lead to difficulty in tolerating cancer therapy and a shortened and lower quality life.
Le Cosquer et al. address the question of the risk of incident cancer among patients with a history of breast cancer. The authors found that the risk was related to poor prognostic factors for breast cancer and not IBD therapy. This should be interpreted with caution as the numbers, though the largest reported, are 207 patients. After propensity score matching, crude incidence rates per 1000 person years appeared greater in the treatment arm (28.9) versus the untreated arm (10.2), P = .0519. With a greater number of patients, it is conceivable the difference is significant.
On the flip side, prior to diagnosis, the majority of IBD patients received immunosuppressant or biologic therapy; however, after the index cancer, 51.6% of patients received no treatment. The survival curves show a near 25% difference in favor of treated patients after 300 months, albeit with very small numbers, raising the question of whether withholding IBD therapy is more harmful.
It is reassuring that the multiple papers cited in the article have not shown an increase in solid organ tumors to date. However, the practitioner needs to balance maintenance of IBD remission and overall health with the risk of complications in the patient with underlying malignancy. This complex decision making will shift over time and should involve the patient, the oncologist, and the gastroenterologist. In my practice, thiopurines are avoided and anti-integrins and IL-23s are preferred. However, anti-TNF agents and JAK-inhibitors are used when the patients’ overall benefit from disease control outweighs their (theoretical) risk for recurrence, infection, and thromboembolism.
Uma Mahadevan, MD, AGAF, is the Lynne and Marc Benioff Professor of Gastroenterology, and director of the Colitis and Crohn’s Disease Center at the University of California, San Francisco. She declared research support from the Leona M. and Harry B. Helmsley Trust, and has served as a consultant for multiple pharmaceutical firms.
Patients with inflammatory bowel disease (IBD) are at risk for a host of other illnesses, including cancer, at rates similar to or greater than the general population. When faced with uncertainty about drug safety with a cancer diagnosis, the reflex is to avoid the therapy altogether. This may lead to significant flares which may in turn lead to difficulty in tolerating cancer therapy and a shortened and lower quality life.
Le Cosquer et al. address the question of the risk of incident cancer among patients with a history of breast cancer. The authors found that the risk was related to poor prognostic factors for breast cancer and not IBD therapy. This should be interpreted with caution as the numbers, though the largest reported, are 207 patients. After propensity score matching, crude incidence rates per 1000 person years appeared greater in the treatment arm (28.9) versus the untreated arm (10.2), P = .0519. With a greater number of patients, it is conceivable the difference is significant.
On the flip side, prior to diagnosis, the majority of IBD patients received immunosuppressant or biologic therapy; however, after the index cancer, 51.6% of patients received no treatment. The survival curves show a near 25% difference in favor of treated patients after 300 months, albeit with very small numbers, raising the question of whether withholding IBD therapy is more harmful.
It is reassuring that the multiple papers cited in the article have not shown an increase in solid organ tumors to date. However, the practitioner needs to balance maintenance of IBD remission and overall health with the risk of complications in the patient with underlying malignancy. This complex decision making will shift over time and should involve the patient, the oncologist, and the gastroenterologist. In my practice, thiopurines are avoided and anti-integrins and IL-23s are preferred. However, anti-TNF agents and JAK-inhibitors are used when the patients’ overall benefit from disease control outweighs their (theoretical) risk for recurrence, infection, and thromboembolism.
Uma Mahadevan, MD, AGAF, is the Lynne and Marc Benioff Professor of Gastroenterology, and director of the Colitis and Crohn’s Disease Center at the University of California, San Francisco. She declared research support from the Leona M. and Harry B. Helmsley Trust, and has served as a consultant for multiple pharmaceutical firms.
Patients with inflammatory bowel disease (IBD) are at risk for a host of other illnesses, including cancer, at rates similar to or greater than the general population. When faced with uncertainty about drug safety with a cancer diagnosis, the reflex is to avoid the therapy altogether. This may lead to significant flares which may in turn lead to difficulty in tolerating cancer therapy and a shortened and lower quality life.
Le Cosquer et al. address the question of the risk of incident cancer among patients with a history of breast cancer. The authors found that the risk was related to poor prognostic factors for breast cancer and not IBD therapy. This should be interpreted with caution as the numbers, though the largest reported, are 207 patients. After propensity score matching, crude incidence rates per 1000 person years appeared greater in the treatment arm (28.9) versus the untreated arm (10.2), P = .0519. With a greater number of patients, it is conceivable the difference is significant.
On the flip side, prior to diagnosis, the majority of IBD patients received immunosuppressant or biologic therapy; however, after the index cancer, 51.6% of patients received no treatment. The survival curves show a near 25% difference in favor of treated patients after 300 months, albeit with very small numbers, raising the question of whether withholding IBD therapy is more harmful.
It is reassuring that the multiple papers cited in the article have not shown an increase in solid organ tumors to date. However, the practitioner needs to balance maintenance of IBD remission and overall health with the risk of complications in the patient with underlying malignancy. This complex decision making will shift over time and should involve the patient, the oncologist, and the gastroenterologist. In my practice, thiopurines are avoided and anti-integrins and IL-23s are preferred. However, anti-TNF agents and JAK-inhibitors are used when the patients’ overall benefit from disease control outweighs their (theoretical) risk for recurrence, infection, and thromboembolism.
Uma Mahadevan, MD, AGAF, is the Lynne and Marc Benioff Professor of Gastroenterology, and director of the Colitis and Crohn’s Disease Center at the University of California, San Francisco. She declared research support from the Leona M. and Harry B. Helmsley Trust, and has served as a consultant for multiple pharmaceutical firms.
, according to investigators.
These findings diminish concerns that IBD therapy could theoretically reactivate dormant micrometastases, lead author Guillaume Le Cosquer, MD, of Toulouse University Hospital, Toulouse, France, and colleagues, reported.
“In patients with IBD, medical management of subjects with a history of breast cancer is a frequent and unresolved problem for clinicians,” the investigators wrote in Clinical Gastroenterology and Hepatology (2024 Nov. doi: 10.1016/j.cgh.2024.09.034).
Previous studies have reported that conventional immunosuppressants and biologics do not increase risk of incident cancer among IBD patients with a prior nondigestive malignancy; however, recent guidelines from the European Crohn’s and Colitis Organisation (ECCO) suggest that data are insufficient to make associated recommendations, prompting the present study.
“[T]he major strength of our work is that it is the first to focus on the most frequent cancer (breast cancer) in patients with IBD only, with the longest follow-up after breast cancer in patients with IBD ever published,” Dr. Le Cosquer and colleagues noted.
The dataset included 207 patients with IBD and a history of breast cancer, drawn from 7 tertiary centers across France.
The index date was the time of breast cancer diagnosis, and patients were followed for a median of 71 months. The median time from cancer diagnosis to initiation of IBD treatment was 28 months.
First-line post-cancer treatments included conventional immunosuppressants (19.3%), anti–tumor necrosis factor (anti-TNF) agents (19.8%), vedolizumab (7.2%), and ustekinumab (1.9%). Approximately half (51.6%) received no immunosuppressive therapy during follow-up.
Over the study period, 42 incident cancers were recorded (20.3%), among which 34 were breast cancer recurrences. Adjusted incidence rates per 1000 person-years were 10.2 (95% CI, 6.0–16.4) in the untreated group and 28.9 (95% CI, 11.6–59.6) in patients exposed to immunosuppressive or biologic therapies (P = .0519). Incident cancer–free survival did not differ significantly between treated and untreated groups (P = .4796).
On multivariable analysis, independent predictors of incident cancer included T4d stage (P = .036), triple-negative status (P = .016), and follow-up duration shorter than 71 months (P = .005).
“[I]mmunosuppressant and biologic use in selected patients with IBD with prior breast cancer does not seem to increase the risk of incident cancer,” the investigators wrote, noting that the main predictors of cancer recurrence were known poor prognostic features of breast cancer.
Dr. Le Cosquer and colleagues acknowledged a lack of prospective safety data for biologic therapies among patients with prior malignancy, as these individuals are often excluded from clinical trials. Still, they underscored alignment between their findings and earlier retrospective studies, including analyses from the SAPPHIRE registry and Medicare data, which also found no significant increase in breast cancer recurrence with anti-TNF agents or newer biologics such as vedolizumab and ustekinumab.
“Our findings will help clinicians to make decisions in multidisciplinary meetings to start immunosuppressants or biologics in case of IBD flare-up in these patients,” they concluded.
The investigators disclosed relationships with AbbVie, Janssen, Takeda, and others.
, according to investigators.
These findings diminish concerns that IBD therapy could theoretically reactivate dormant micrometastases, lead author Guillaume Le Cosquer, MD, of Toulouse University Hospital, Toulouse, France, and colleagues, reported.
“In patients with IBD, medical management of subjects with a history of breast cancer is a frequent and unresolved problem for clinicians,” the investigators wrote in Clinical Gastroenterology and Hepatology (2024 Nov. doi: 10.1016/j.cgh.2024.09.034).
Previous studies have reported that conventional immunosuppressants and biologics do not increase risk of incident cancer among IBD patients with a prior nondigestive malignancy; however, recent guidelines from the European Crohn’s and Colitis Organisation (ECCO) suggest that data are insufficient to make associated recommendations, prompting the present study.
“[T]he major strength of our work is that it is the first to focus on the most frequent cancer (breast cancer) in patients with IBD only, with the longest follow-up after breast cancer in patients with IBD ever published,” Dr. Le Cosquer and colleagues noted.
The dataset included 207 patients with IBD and a history of breast cancer, drawn from 7 tertiary centers across France.
The index date was the time of breast cancer diagnosis, and patients were followed for a median of 71 months. The median time from cancer diagnosis to initiation of IBD treatment was 28 months.
First-line post-cancer treatments included conventional immunosuppressants (19.3%), anti–tumor necrosis factor (anti-TNF) agents (19.8%), vedolizumab (7.2%), and ustekinumab (1.9%). Approximately half (51.6%) received no immunosuppressive therapy during follow-up.
Over the study period, 42 incident cancers were recorded (20.3%), among which 34 were breast cancer recurrences. Adjusted incidence rates per 1000 person-years were 10.2 (95% CI, 6.0–16.4) in the untreated group and 28.9 (95% CI, 11.6–59.6) in patients exposed to immunosuppressive or biologic therapies (P = .0519). Incident cancer–free survival did not differ significantly between treated and untreated groups (P = .4796).
On multivariable analysis, independent predictors of incident cancer included T4d stage (P = .036), triple-negative status (P = .016), and follow-up duration shorter than 71 months (P = .005).
“[I]mmunosuppressant and biologic use in selected patients with IBD with prior breast cancer does not seem to increase the risk of incident cancer,” the investigators wrote, noting that the main predictors of cancer recurrence were known poor prognostic features of breast cancer.
Dr. Le Cosquer and colleagues acknowledged a lack of prospective safety data for biologic therapies among patients with prior malignancy, as these individuals are often excluded from clinical trials. Still, they underscored alignment between their findings and earlier retrospective studies, including analyses from the SAPPHIRE registry and Medicare data, which also found no significant increase in breast cancer recurrence with anti-TNF agents or newer biologics such as vedolizumab and ustekinumab.
“Our findings will help clinicians to make decisions in multidisciplinary meetings to start immunosuppressants or biologics in case of IBD flare-up in these patients,” they concluded.
The investigators disclosed relationships with AbbVie, Janssen, Takeda, and others.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Hypothyroidism Linked to Gut Microbiome Disturbances
, according to results of a study.
“[The research] supports the idea that improving gut health could have far-reaching effects beyond digestion, possibly even helping to prevent autoimmune diseases, such as Hashimoto thyroiditis,” said senior author Ruchi Mathur, MD, director of the Diabetes Outpatient Treatment and Education Center and director of Clinical Operations of Medically Associated Science and Technology, at Cedars-Sinai in Los Angeles, in a press statement for the study, which was presented at ENDO 2025: The Endocrine Society Annual Meeting.
“These findings open the door to new screening and prevention strategies,” Mathur added. “For example, doctors may begin to monitor thyroid health more closely in patients with SIBO, and vice versa.”
With some small studies previously suggesting an association between the gut microbiome and hypothyroidism, Mathur and colleagues further explored the relationship in two analyses.
Assessing the Role of the Small Bowel
For the first, they evaluated data on 49 patients with Hashimoto thyroiditis (HT) and 323 controls without the condition from their REIMAGINE trial, which included small bowel fluid samples from upper endoscopies and DNA sequencing.
In the study, all patients with HT were treated with thyroid replacement (levothyroxine), hence, there were notably no significant differences between the two groups in terms of thyroid stimulating hormone (TSH) levels.
Despite the lack of those differences, patients with HT had a prevalence of SIBO more than twice that of the control group, independent of gender (33% vs 15%; odds ratio, 2.71; P = .005).
When the two groups were further subdivided into two groups each — those with and without SIBO — significant further variations of microbial diversity were observed between those with and without HT, Mathur told GI & Hepatology News.
“Interestingly, we saw the small bowel microbiome was not only different in SIBO-positive patients, including higher gram negatives, which is to be expected, but that the presence or absence of hypothyroidism itself was associated with specific patterns of these gram-negative bacteria,” she explained.
“In addition, when we looked at hypothyroidism without SIBO present, there were also changes between groups, such as higher Neisseria in the hypothyroid group.”
“All these findings are novel as this is the first paper to look specifically at the small bowel,” she added, noting that previous smaller studies have focused more on evaluation of stool samples.
“We believe the small bowel is the most metabolically active area of the intestine and plays an important role in metabolism,” Mathur noted. “Thus, the microbial changes here are likely more physiologically significant than the patterns seen in stool.”
Further Findings from a Large Population
In a separate analysis, the team evaluated data from the TriNetX database on the 10-year incidence of developing SIBO among 1.1 million subjects with hypothyroidism in the US compared with 1 million controls.
They found that people with hypothyroidism were approximately twice as likely to develop SIBO compared with those without hypothyroidism (relative risk [RR], 2.20).
Furthermore, those with HT, in particular, had an even higher risk, at 2.4 times the controls (RR, 2.40).
Treatment with levothyroxine decreased the risk of developing SIBO in hypothyroidism (RR, 0.33) and HT (RR, 0.78) vs those who did not receive treatment.
Mechanisms?
However, the fact that differences in SIBO were observed even between people who were treated for HT and those without the condition in the first analysis, and hence had similar TSH levels, was notable, Mathur said.
“This suggests that perhaps there are other factors aside from TSH levels and free T4 that are at play here,” she said. “Some people have theorized that perhaps delayed gut motility in hypothyroidism promotes the development of SIBO; however, there are many other factors within this complex interplay between the microbiome and the thyroid that could also be playing a role.”
“For example, SIBO leads to inflammation and weakening of the gut barrier,” Mathur explained.
Furthermore, “levothyroxine absorption and cycling of the thyroid hormone occurs predominantly in the small bowel, [while the] microbiome plays a key role in the absorption of iron, selenium, iodine, and zinc, which are critical for thyroid function.”
Overall, “further research is needed to understand how the mechanisms are affected during the development of SIBO and hypothyroidism,” Mathur said.
Assessment of Changes Over Time Anticipated
Commenting on the research, Gregory A. Brent, MD, senior executive academic vice-chair of the Department of Medicine and professor of medicine and physiology at the David Geffen School of Medicine at University of California Los Angeles said the study is indeed novel.
“This, to my knowledge, is the first investigation to link characteristics of the small bowel microbiome with hypothyroidism,” Brent told GI & Hepatology News.
While any clinical significance has yet to be determined, “the association of these small bowel microbiome changes with hypothyroidism may have implications for contributing to the onset of autoimmune hypothyroidism in susceptible populations as well as influences on levothyroxine absorption in hypothyroid patients on levothyroxine therapy,” Brent said.
With the SIBO differences observed even among treated patients with vs without HT, “it seems less likely that the microbiome changes are the result of reduced thyroid hormone signaling,” Brent noted.
Furthermore, a key piece of the puzzle will be to observe the microbiome changes over time, he added.
“These studies were at a single time point [and] longitudinal studies will be especially important to see how the association changes over time and are influenced by the treatment of hypothyroidism and of SIBO,” Brent said.
The authors and Brent had no disclosures to report.
A version of this article appeared on Medscape.com.
, according to results of a study.
“[The research] supports the idea that improving gut health could have far-reaching effects beyond digestion, possibly even helping to prevent autoimmune diseases, such as Hashimoto thyroiditis,” said senior author Ruchi Mathur, MD, director of the Diabetes Outpatient Treatment and Education Center and director of Clinical Operations of Medically Associated Science and Technology, at Cedars-Sinai in Los Angeles, in a press statement for the study, which was presented at ENDO 2025: The Endocrine Society Annual Meeting.
“These findings open the door to new screening and prevention strategies,” Mathur added. “For example, doctors may begin to monitor thyroid health more closely in patients with SIBO, and vice versa.”
With some small studies previously suggesting an association between the gut microbiome and hypothyroidism, Mathur and colleagues further explored the relationship in two analyses.
Assessing the Role of the Small Bowel
For the first, they evaluated data on 49 patients with Hashimoto thyroiditis (HT) and 323 controls without the condition from their REIMAGINE trial, which included small bowel fluid samples from upper endoscopies and DNA sequencing.
In the study, all patients with HT were treated with thyroid replacement (levothyroxine), hence, there were notably no significant differences between the two groups in terms of thyroid stimulating hormone (TSH) levels.
Despite the lack of those differences, patients with HT had a prevalence of SIBO more than twice that of the control group, independent of gender (33% vs 15%; odds ratio, 2.71; P = .005).
When the two groups were further subdivided into two groups each — those with and without SIBO — significant further variations of microbial diversity were observed between those with and without HT, Mathur told GI & Hepatology News.
“Interestingly, we saw the small bowel microbiome was not only different in SIBO-positive patients, including higher gram negatives, which is to be expected, but that the presence or absence of hypothyroidism itself was associated with specific patterns of these gram-negative bacteria,” she explained.
“In addition, when we looked at hypothyroidism without SIBO present, there were also changes between groups, such as higher Neisseria in the hypothyroid group.”
“All these findings are novel as this is the first paper to look specifically at the small bowel,” she added, noting that previous smaller studies have focused more on evaluation of stool samples.
“We believe the small bowel is the most metabolically active area of the intestine and plays an important role in metabolism,” Mathur noted. “Thus, the microbial changes here are likely more physiologically significant than the patterns seen in stool.”
Further Findings from a Large Population
In a separate analysis, the team evaluated data from the TriNetX database on the 10-year incidence of developing SIBO among 1.1 million subjects with hypothyroidism in the US compared with 1 million controls.
They found that people with hypothyroidism were approximately twice as likely to develop SIBO compared with those without hypothyroidism (relative risk [RR], 2.20).
Furthermore, those with HT, in particular, had an even higher risk, at 2.4 times the controls (RR, 2.40).
Treatment with levothyroxine decreased the risk of developing SIBO in hypothyroidism (RR, 0.33) and HT (RR, 0.78) vs those who did not receive treatment.
Mechanisms?
However, the fact that differences in SIBO were observed even between people who were treated for HT and those without the condition in the first analysis, and hence had similar TSH levels, was notable, Mathur said.
“This suggests that perhaps there are other factors aside from TSH levels and free T4 that are at play here,” she said. “Some people have theorized that perhaps delayed gut motility in hypothyroidism promotes the development of SIBO; however, there are many other factors within this complex interplay between the microbiome and the thyroid that could also be playing a role.”
“For example, SIBO leads to inflammation and weakening of the gut barrier,” Mathur explained.
Furthermore, “levothyroxine absorption and cycling of the thyroid hormone occurs predominantly in the small bowel, [while the] microbiome plays a key role in the absorption of iron, selenium, iodine, and zinc, which are critical for thyroid function.”
Overall, “further research is needed to understand how the mechanisms are affected during the development of SIBO and hypothyroidism,” Mathur said.
Assessment of Changes Over Time Anticipated
Commenting on the research, Gregory A. Brent, MD, senior executive academic vice-chair of the Department of Medicine and professor of medicine and physiology at the David Geffen School of Medicine at University of California Los Angeles said the study is indeed novel.
“This, to my knowledge, is the first investigation to link characteristics of the small bowel microbiome with hypothyroidism,” Brent told GI & Hepatology News.
While any clinical significance has yet to be determined, “the association of these small bowel microbiome changes with hypothyroidism may have implications for contributing to the onset of autoimmune hypothyroidism in susceptible populations as well as influences on levothyroxine absorption in hypothyroid patients on levothyroxine therapy,” Brent said.
With the SIBO differences observed even among treated patients with vs without HT, “it seems less likely that the microbiome changes are the result of reduced thyroid hormone signaling,” Brent noted.
Furthermore, a key piece of the puzzle will be to observe the microbiome changes over time, he added.
“These studies were at a single time point [and] longitudinal studies will be especially important to see how the association changes over time and are influenced by the treatment of hypothyroidism and of SIBO,” Brent said.
The authors and Brent had no disclosures to report.
A version of this article appeared on Medscape.com.
, according to results of a study.
“[The research] supports the idea that improving gut health could have far-reaching effects beyond digestion, possibly even helping to prevent autoimmune diseases, such as Hashimoto thyroiditis,” said senior author Ruchi Mathur, MD, director of the Diabetes Outpatient Treatment and Education Center and director of Clinical Operations of Medically Associated Science and Technology, at Cedars-Sinai in Los Angeles, in a press statement for the study, which was presented at ENDO 2025: The Endocrine Society Annual Meeting.
“These findings open the door to new screening and prevention strategies,” Mathur added. “For example, doctors may begin to monitor thyroid health more closely in patients with SIBO, and vice versa.”
With some small studies previously suggesting an association between the gut microbiome and hypothyroidism, Mathur and colleagues further explored the relationship in two analyses.
Assessing the Role of the Small Bowel
For the first, they evaluated data on 49 patients with Hashimoto thyroiditis (HT) and 323 controls without the condition from their REIMAGINE trial, which included small bowel fluid samples from upper endoscopies and DNA sequencing.
In the study, all patients with HT were treated with thyroid replacement (levothyroxine), hence, there were notably no significant differences between the two groups in terms of thyroid stimulating hormone (TSH) levels.
Despite the lack of those differences, patients with HT had a prevalence of SIBO more than twice that of the control group, independent of gender (33% vs 15%; odds ratio, 2.71; P = .005).
When the two groups were further subdivided into two groups each — those with and without SIBO — significant further variations of microbial diversity were observed between those with and without HT, Mathur told GI & Hepatology News.
“Interestingly, we saw the small bowel microbiome was not only different in SIBO-positive patients, including higher gram negatives, which is to be expected, but that the presence or absence of hypothyroidism itself was associated with specific patterns of these gram-negative bacteria,” she explained.
“In addition, when we looked at hypothyroidism without SIBO present, there were also changes between groups, such as higher Neisseria in the hypothyroid group.”
“All these findings are novel as this is the first paper to look specifically at the small bowel,” she added, noting that previous smaller studies have focused more on evaluation of stool samples.
“We believe the small bowel is the most metabolically active area of the intestine and plays an important role in metabolism,” Mathur noted. “Thus, the microbial changes here are likely more physiologically significant than the patterns seen in stool.”
Further Findings from a Large Population
In a separate analysis, the team evaluated data from the TriNetX database on the 10-year incidence of developing SIBO among 1.1 million subjects with hypothyroidism in the US compared with 1 million controls.
They found that people with hypothyroidism were approximately twice as likely to develop SIBO compared with those without hypothyroidism (relative risk [RR], 2.20).
Furthermore, those with HT, in particular, had an even higher risk, at 2.4 times the controls (RR, 2.40).
Treatment with levothyroxine decreased the risk of developing SIBO in hypothyroidism (RR, 0.33) and HT (RR, 0.78) vs those who did not receive treatment.
Mechanisms?
However, the fact that differences in SIBO were observed even between people who were treated for HT and those without the condition in the first analysis, and hence had similar TSH levels, was notable, Mathur said.
“This suggests that perhaps there are other factors aside from TSH levels and free T4 that are at play here,” she said. “Some people have theorized that perhaps delayed gut motility in hypothyroidism promotes the development of SIBO; however, there are many other factors within this complex interplay between the microbiome and the thyroid that could also be playing a role.”
“For example, SIBO leads to inflammation and weakening of the gut barrier,” Mathur explained.
Furthermore, “levothyroxine absorption and cycling of the thyroid hormone occurs predominantly in the small bowel, [while the] microbiome plays a key role in the absorption of iron, selenium, iodine, and zinc, which are critical for thyroid function.”
Overall, “further research is needed to understand how the mechanisms are affected during the development of SIBO and hypothyroidism,” Mathur said.
Assessment of Changes Over Time Anticipated
Commenting on the research, Gregory A. Brent, MD, senior executive academic vice-chair of the Department of Medicine and professor of medicine and physiology at the David Geffen School of Medicine at University of California Los Angeles said the study is indeed novel.
“This, to my knowledge, is the first investigation to link characteristics of the small bowel microbiome with hypothyroidism,” Brent told GI & Hepatology News.
While any clinical significance has yet to be determined, “the association of these small bowel microbiome changes with hypothyroidism may have implications for contributing to the onset of autoimmune hypothyroidism in susceptible populations as well as influences on levothyroxine absorption in hypothyroid patients on levothyroxine therapy,” Brent said.
With the SIBO differences observed even among treated patients with vs without HT, “it seems less likely that the microbiome changes are the result of reduced thyroid hormone signaling,” Brent noted.
Furthermore, a key piece of the puzzle will be to observe the microbiome changes over time, he added.
“These studies were at a single time point [and] longitudinal studies will be especially important to see how the association changes over time and are influenced by the treatment of hypothyroidism and of SIBO,” Brent said.
The authors and Brent had no disclosures to report.
A version of this article appeared on Medscape.com.
Sleep Changes in IBD Could Signal Inflammation, Flareups
, an observational study suggested.
Sleep data from 101 study participants over a mean duration of about 228 days revealed that altered sleep architecture was only apparent when inflammation was present — symptoms alone did not impact sleep cycles or signal inflammation.
“We thought symptoms might have an impact on sleep, but interestingly, our data showed that measurable changes like reduced rapid eye movement (REM) sleep and increased light sleep only occurred during periods of active inflammation,” Robert Hirten, MD, associate professor of Medicine (Gastroenterology), and Artificial Intelligence and Human Health, at the Icahn School of Medicine at Mount Sinai, New York City, told GI & Hepatology News.
“It was also interesting to see distinct patterns in sleep metrics begin to shift over the 45 days before a flare, suggesting the potential for sleep to serve as an early indicator of disease activity,” he added.
“Sleep is often overlooked in the management of IBD, but it may provide valuable insights into a patient’s underlying disease state,” he said. “While sleep monitoring isn’t yet a standard part of IBD care, this study highlights its potential as a noninvasive window into disease activity, and a promising area for future clinical integration.”
The study was published online in Clinical Gastroenterology and Hepatology.
Less REM Sleep, More Light Sleep
Researchers assessed the impact of inflammation and symptoms on sleep architecture in IBD by analyzing data from 101 individuals who answered daily disease activity surveys and wore a wearable device.
The mean age of participants was 41 years and 65.3% were women. Sixty-three participants (62.4%) had Crohn’s disease (CD) and 38 (37.6%) had ulcerative colitis (UC).
Almost 40 (39.6%) participants used an Apple Watch; 50 (49.5%) used a Fitbit; and 11 (10.9%) used an Oura ring. Sleep architecture, sleep efficiency, and total hours asleep were collected from the devices. Participants were encouraged to wear their devices for at least 4 days per week and 8 hours per day and were not required to wear them at night. Participants provided data by linking their devices to ehive, Mount Sinai’s custom app.
Daily clinical disease activity was assessed using the UC or CD Patient Reported Outcome-2 survey. Participants were asked to answer at least four daily surveys each week.
Associations between sleep metrics and periods of symptomatic and inflammatory flares, and combinations of symptomatic and inflammatory activity, were compared to periods of symptomatic and inflammatory remission.
Furthermore, researchers explored the rate of change in sleep metrics for 45 days before and after inflammatory and symptomatic flares.
Participants contributed a mean duration of 228.16 nights of wearable data. During active inflammation, they spent a lower percentage of sleep time in REM (20% vs 21.59%) and a greater percentage of sleep time in light sleep (62.23% vs 59.95%) than during inflammatory remission. No differences were observed in the mean percentage of time in deep sleep, sleep efficiency, or total time asleep.
During symptomatic flares, there were no differences in the percentage of sleep time in REM sleep, deep sleep, light sleep, or sleep efficiency compared with periods of inflammatory remission. However, participants slept less overall during symptomatic flares compared with during symptomatic remission.
Compared with during asymptomatic and uninflamed periods, during asymptomatic but inflamed periods, participants spent a lower percentage of time in REM sleep, and more time in light sleep; however, there were no differences in sleep efficiency or total time asleep.
Similarly, participants had more light sleep and less REM sleep during symptomatic and inflammatory flares than during asymptomatic and uninflamed periods — but there were no differences in the percentage of time spent in deep sleep, in sleep efficiency, and the total time asleep.
Symptomatic flares alone, without inflammation, did not impact sleep metrics, the researchers concluded. However, periods with active inflammation were associated with a significantly smaller percentage of sleep time in REM sleep and a greater percentage of sleep time in light sleep.
The team also performed longitudinal mapping of sleep patterns before, during, and after disease exacerbations by analyzing sleep data for 6 weeks before and 6 weeks after flare episodes.
They found that sleep disturbances significantly worsen leading up to inflammatory flares and improve afterward, suggesting that sleep changes may signal upcoming increased disease activity. Evaluating the intersection of inflammatory and symptomatic flares, altered sleep architecture was only evident when inflammation was present.
“These findings raise important questions about whether intervening on sleep can actually impact inflammation or disease trajectory in IBD,” Hirten said. “Next steps include studying whether targeted sleep interventions can improve both sleep and IBD outcomes.”
While this research is still in the early stages, he said, “it suggests that sleep may have a relationship with inflammatory activity in IBD. For patients, it reinforces the value of paying attention to sleep changes.”
The findings also show the potential of wearable devices to guide more personalized monitoring, he added. “More work is needed before sleep metrics can be used routinely in clinical decision-making.”
Validates the Use of Wearables
Commenting on the study for GI & Hepatology News, Michael Mintz, MD, a gastroenterologist at Weill Cornell Medicine and NewYork-Presbyterian in New York City, observed, “Gastrointestinal symptoms often do not correlate with objective disease activity in IBD, creating a diagnostic challenge for gastroenterologists. Burdensome, expensive, and/or invasive testing, such as colonoscopies, stool tests, or imaging, are frequently required to monitor disease activity.”
“This study is a first step in objectively monitoring inflammation in a patient-centric way that does not create undue burden to our patients,” he said. “It also provides longitudinal data that suggests changes in sleep patterns can pre-date disease flares, which ideally can lead to earlier intervention to prevent disease complications.”
Like Hirten, he noted that clinical decisions, such as changing IBD therapy, should not be based on the results of this study. “Rather this provides validation that wearable technology can provide useful objective data that correlates with disease activity.”
Furthermore, he said, it is not clear whether analyzing sleep data is a cost-effective way of monitoring IBD disease activity, or whether that data should be used alone or in combination with other objective disease markers, to influence clinical decision-making.
“This study provides proof of concept that there is a relationship between sleep characteristics and objective inflammation, but further studies are needed,” he said. “I am hopeful that this technology will give us another tool that we can use in clinical practice to monitor disease activity and improve outcomes in a way that is comfortable and convenient for our patients.”
This study was supported by a grant to Hirten from the US National Institutes of Health. Hirten reported receiving consulting fees from Bristol Meyers Squibb, AbbVie; stock options from Salvo Health; and research support from Janssen, Intralytix, EnLiSense, Crohn’s and Colitis Foundation. Mintz declared no competing interests.
A version of this article appeared on Medscape.com.
, an observational study suggested.
Sleep data from 101 study participants over a mean duration of about 228 days revealed that altered sleep architecture was only apparent when inflammation was present — symptoms alone did not impact sleep cycles or signal inflammation.
“We thought symptoms might have an impact on sleep, but interestingly, our data showed that measurable changes like reduced rapid eye movement (REM) sleep and increased light sleep only occurred during periods of active inflammation,” Robert Hirten, MD, associate professor of Medicine (Gastroenterology), and Artificial Intelligence and Human Health, at the Icahn School of Medicine at Mount Sinai, New York City, told GI & Hepatology News.
“It was also interesting to see distinct patterns in sleep metrics begin to shift over the 45 days before a flare, suggesting the potential for sleep to serve as an early indicator of disease activity,” he added.
“Sleep is often overlooked in the management of IBD, but it may provide valuable insights into a patient’s underlying disease state,” he said. “While sleep monitoring isn’t yet a standard part of IBD care, this study highlights its potential as a noninvasive window into disease activity, and a promising area for future clinical integration.”
The study was published online in Clinical Gastroenterology and Hepatology.
Less REM Sleep, More Light Sleep
Researchers assessed the impact of inflammation and symptoms on sleep architecture in IBD by analyzing data from 101 individuals who answered daily disease activity surveys and wore a wearable device.
The mean age of participants was 41 years and 65.3% were women. Sixty-three participants (62.4%) had Crohn’s disease (CD) and 38 (37.6%) had ulcerative colitis (UC).
Almost 40 (39.6%) participants used an Apple Watch; 50 (49.5%) used a Fitbit; and 11 (10.9%) used an Oura ring. Sleep architecture, sleep efficiency, and total hours asleep were collected from the devices. Participants were encouraged to wear their devices for at least 4 days per week and 8 hours per day and were not required to wear them at night. Participants provided data by linking their devices to ehive, Mount Sinai’s custom app.
Daily clinical disease activity was assessed using the UC or CD Patient Reported Outcome-2 survey. Participants were asked to answer at least four daily surveys each week.
Associations between sleep metrics and periods of symptomatic and inflammatory flares, and combinations of symptomatic and inflammatory activity, were compared to periods of symptomatic and inflammatory remission.
Furthermore, researchers explored the rate of change in sleep metrics for 45 days before and after inflammatory and symptomatic flares.
Participants contributed a mean duration of 228.16 nights of wearable data. During active inflammation, they spent a lower percentage of sleep time in REM (20% vs 21.59%) and a greater percentage of sleep time in light sleep (62.23% vs 59.95%) than during inflammatory remission. No differences were observed in the mean percentage of time in deep sleep, sleep efficiency, or total time asleep.
During symptomatic flares, there were no differences in the percentage of sleep time in REM sleep, deep sleep, light sleep, or sleep efficiency compared with periods of inflammatory remission. However, participants slept less overall during symptomatic flares compared with during symptomatic remission.
Compared with during asymptomatic and uninflamed periods, during asymptomatic but inflamed periods, participants spent a lower percentage of time in REM sleep, and more time in light sleep; however, there were no differences in sleep efficiency or total time asleep.
Similarly, participants had more light sleep and less REM sleep during symptomatic and inflammatory flares than during asymptomatic and uninflamed periods — but there were no differences in the percentage of time spent in deep sleep, in sleep efficiency, and the total time asleep.
Symptomatic flares alone, without inflammation, did not impact sleep metrics, the researchers concluded. However, periods with active inflammation were associated with a significantly smaller percentage of sleep time in REM sleep and a greater percentage of sleep time in light sleep.
The team also performed longitudinal mapping of sleep patterns before, during, and after disease exacerbations by analyzing sleep data for 6 weeks before and 6 weeks after flare episodes.
They found that sleep disturbances significantly worsen leading up to inflammatory flares and improve afterward, suggesting that sleep changes may signal upcoming increased disease activity. Evaluating the intersection of inflammatory and symptomatic flares, altered sleep architecture was only evident when inflammation was present.
“These findings raise important questions about whether intervening on sleep can actually impact inflammation or disease trajectory in IBD,” Hirten said. “Next steps include studying whether targeted sleep interventions can improve both sleep and IBD outcomes.”
While this research is still in the early stages, he said, “it suggests that sleep may have a relationship with inflammatory activity in IBD. For patients, it reinforces the value of paying attention to sleep changes.”
The findings also show the potential of wearable devices to guide more personalized monitoring, he added. “More work is needed before sleep metrics can be used routinely in clinical decision-making.”
Validates the Use of Wearables
Commenting on the study for GI & Hepatology News, Michael Mintz, MD, a gastroenterologist at Weill Cornell Medicine and NewYork-Presbyterian in New York City, observed, “Gastrointestinal symptoms often do not correlate with objective disease activity in IBD, creating a diagnostic challenge for gastroenterologists. Burdensome, expensive, and/or invasive testing, such as colonoscopies, stool tests, or imaging, are frequently required to monitor disease activity.”
“This study is a first step in objectively monitoring inflammation in a patient-centric way that does not create undue burden to our patients,” he said. “It also provides longitudinal data that suggests changes in sleep patterns can pre-date disease flares, which ideally can lead to earlier intervention to prevent disease complications.”
Like Hirten, he noted that clinical decisions, such as changing IBD therapy, should not be based on the results of this study. “Rather this provides validation that wearable technology can provide useful objective data that correlates with disease activity.”
Furthermore, he said, it is not clear whether analyzing sleep data is a cost-effective way of monitoring IBD disease activity, or whether that data should be used alone or in combination with other objective disease markers, to influence clinical decision-making.
“This study provides proof of concept that there is a relationship between sleep characteristics and objective inflammation, but further studies are needed,” he said. “I am hopeful that this technology will give us another tool that we can use in clinical practice to monitor disease activity and improve outcomes in a way that is comfortable and convenient for our patients.”
This study was supported by a grant to Hirten from the US National Institutes of Health. Hirten reported receiving consulting fees from Bristol Meyers Squibb, AbbVie; stock options from Salvo Health; and research support from Janssen, Intralytix, EnLiSense, Crohn’s and Colitis Foundation. Mintz declared no competing interests.
A version of this article appeared on Medscape.com.
, an observational study suggested.
Sleep data from 101 study participants over a mean duration of about 228 days revealed that altered sleep architecture was only apparent when inflammation was present — symptoms alone did not impact sleep cycles or signal inflammation.
“We thought symptoms might have an impact on sleep, but interestingly, our data showed that measurable changes like reduced rapid eye movement (REM) sleep and increased light sleep only occurred during periods of active inflammation,” Robert Hirten, MD, associate professor of Medicine (Gastroenterology), and Artificial Intelligence and Human Health, at the Icahn School of Medicine at Mount Sinai, New York City, told GI & Hepatology News.
“It was also interesting to see distinct patterns in sleep metrics begin to shift over the 45 days before a flare, suggesting the potential for sleep to serve as an early indicator of disease activity,” he added.
“Sleep is often overlooked in the management of IBD, but it may provide valuable insights into a patient’s underlying disease state,” he said. “While sleep monitoring isn’t yet a standard part of IBD care, this study highlights its potential as a noninvasive window into disease activity, and a promising area for future clinical integration.”
The study was published online in Clinical Gastroenterology and Hepatology.
Less REM Sleep, More Light Sleep
Researchers assessed the impact of inflammation and symptoms on sleep architecture in IBD by analyzing data from 101 individuals who answered daily disease activity surveys and wore a wearable device.
The mean age of participants was 41 years and 65.3% were women. Sixty-three participants (62.4%) had Crohn’s disease (CD) and 38 (37.6%) had ulcerative colitis (UC).
Almost 40 (39.6%) participants used an Apple Watch; 50 (49.5%) used a Fitbit; and 11 (10.9%) used an Oura ring. Sleep architecture, sleep efficiency, and total hours asleep were collected from the devices. Participants were encouraged to wear their devices for at least 4 days per week and 8 hours per day and were not required to wear them at night. Participants provided data by linking their devices to ehive, Mount Sinai’s custom app.
Daily clinical disease activity was assessed using the UC or CD Patient Reported Outcome-2 survey. Participants were asked to answer at least four daily surveys each week.
Associations between sleep metrics and periods of symptomatic and inflammatory flares, and combinations of symptomatic and inflammatory activity, were compared to periods of symptomatic and inflammatory remission.
Furthermore, researchers explored the rate of change in sleep metrics for 45 days before and after inflammatory and symptomatic flares.
Participants contributed a mean duration of 228.16 nights of wearable data. During active inflammation, they spent a lower percentage of sleep time in REM (20% vs 21.59%) and a greater percentage of sleep time in light sleep (62.23% vs 59.95%) than during inflammatory remission. No differences were observed in the mean percentage of time in deep sleep, sleep efficiency, or total time asleep.
During symptomatic flares, there were no differences in the percentage of sleep time in REM sleep, deep sleep, light sleep, or sleep efficiency compared with periods of inflammatory remission. However, participants slept less overall during symptomatic flares compared with during symptomatic remission.
Compared with during asymptomatic and uninflamed periods, during asymptomatic but inflamed periods, participants spent a lower percentage of time in REM sleep, and more time in light sleep; however, there were no differences in sleep efficiency or total time asleep.
Similarly, participants had more light sleep and less REM sleep during symptomatic and inflammatory flares than during asymptomatic and uninflamed periods — but there were no differences in the percentage of time spent in deep sleep, in sleep efficiency, and the total time asleep.
Symptomatic flares alone, without inflammation, did not impact sleep metrics, the researchers concluded. However, periods with active inflammation were associated with a significantly smaller percentage of sleep time in REM sleep and a greater percentage of sleep time in light sleep.
The team also performed longitudinal mapping of sleep patterns before, during, and after disease exacerbations by analyzing sleep data for 6 weeks before and 6 weeks after flare episodes.
They found that sleep disturbances significantly worsen leading up to inflammatory flares and improve afterward, suggesting that sleep changes may signal upcoming increased disease activity. Evaluating the intersection of inflammatory and symptomatic flares, altered sleep architecture was only evident when inflammation was present.
“These findings raise important questions about whether intervening on sleep can actually impact inflammation or disease trajectory in IBD,” Hirten said. “Next steps include studying whether targeted sleep interventions can improve both sleep and IBD outcomes.”
While this research is still in the early stages, he said, “it suggests that sleep may have a relationship with inflammatory activity in IBD. For patients, it reinforces the value of paying attention to sleep changes.”
The findings also show the potential of wearable devices to guide more personalized monitoring, he added. “More work is needed before sleep metrics can be used routinely in clinical decision-making.”
Validates the Use of Wearables
Commenting on the study for GI & Hepatology News, Michael Mintz, MD, a gastroenterologist at Weill Cornell Medicine and NewYork-Presbyterian in New York City, observed, “Gastrointestinal symptoms often do not correlate with objective disease activity in IBD, creating a diagnostic challenge for gastroenterologists. Burdensome, expensive, and/or invasive testing, such as colonoscopies, stool tests, or imaging, are frequently required to monitor disease activity.”
“This study is a first step in objectively monitoring inflammation in a patient-centric way that does not create undue burden to our patients,” he said. “It also provides longitudinal data that suggests changes in sleep patterns can pre-date disease flares, which ideally can lead to earlier intervention to prevent disease complications.”
Like Hirten, he noted that clinical decisions, such as changing IBD therapy, should not be based on the results of this study. “Rather this provides validation that wearable technology can provide useful objective data that correlates with disease activity.”
Furthermore, he said, it is not clear whether analyzing sleep data is a cost-effective way of monitoring IBD disease activity, or whether that data should be used alone or in combination with other objective disease markers, to influence clinical decision-making.
“This study provides proof of concept that there is a relationship between sleep characteristics and objective inflammation, but further studies are needed,” he said. “I am hopeful that this technology will give us another tool that we can use in clinical practice to monitor disease activity and improve outcomes in a way that is comfortable and convenient for our patients.”
This study was supported by a grant to Hirten from the US National Institutes of Health. Hirten reported receiving consulting fees from Bristol Meyers Squibb, AbbVie; stock options from Salvo Health; and research support from Janssen, Intralytix, EnLiSense, Crohn’s and Colitis Foundation. Mintz declared no competing interests.
A version of this article appeared on Medscape.com.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Dietary Trial Shows Benefits of a Low Emulsifier Diet for Crohn’s Disease
WASHINGTON, DC — involving 154 patients with mildly active disease living across the United Kingdom.
The findings were reported at Gut Microbiota for Health (GMFH) World Summit 2025 by Benoit Chassaing, PhD, of the Institut Pasteur, Paris, France, whose research leading up to the trial has demonstrated that food additive emulsifiers —ubiquitous in processed foods — alter microbiota composition and lead to microbiota encroachment into the mucus layer of the gut and subsequent chronic gut inflammation.
Patients in the ADDapt trial, which was also reported in an abstract earlier this year at the European Crohn’s and Colitis Organization (ECCO) 2025 Congress, had a Crohn’s disease activity index (CDAI) of 150-250 and evidence of inflammation (faecal calprotectin (FCP) ≥ 150 µg/g or endoscopy/radiology). All “had been exposed in their regular diets to emulsifiers,” said Chassaing, a co-investigator, during a GMFH session on “Dietary Drivers of Health and Disease.”
They were randomized to either a low-emulsifier diet or to a low-emulsifier diet followed by emulsifier “resupplementation” — a design meant to “account for the very strong placebo effect that is always observed with dietary studies,” he said.
All patients received dietary counseling, a smart phone app and barcode scan to support shopping, and weekly support. They also received supermarket foods for 25% of their needs that were either free of emulsifiers or contained emulsifiers, and they were provided three snacks per day that were emulsifier-free or contained carrageenan, carboxymethycellulse (CMC), and polysorbate-80 (P80) — dietary emulsifiers that are commonly added to processed foods to enhance texture and extend shelf-life.
In the intention-to-treat (ITT) analysis, 49% of patients in the intervention group reached the primary endpoint of a 70-point reduction or more in CDAI response after 8 weeks compared with 31% of those in the control group (P = .019), with an adjusted relative risk of response of 3.1 (P = .003), Chassaing shared at the GMFH meeting, convened by the American Gastroenterological Association and the European Society of Neurogastroenterology and Motility.
In the per-protocol analysis (n = 119), 61% and 47% of patients in the intervention and control groups, respectively, reached the primary outcome of CDAI response, with an adjusted relative risk of response of 3.0 (P = .018), he said.
Secondary endpoints included CDAI remission at 24 weeks, and according to the abstract for the ECCO Congress, in the ITT analysis, patients in the intervention group were more than twice as likely to experience remission.
Chassaing noted at the GMFH meeting that as part of the study, he and coinvestigators have been investigating the participants’ gut microbiota with metagenomic analyses. The study was led by Kevin Whelan, PhD, head of the Department of Nutritional Sciences at King’s College London, London, England.
Can Emulsifier-Sensitive Individuals Be Identified?
In murine model research 10 years ago, Chassaing showed that the administration of CMC and P80 results in microbiota encroachment into the mucus layer of the gut, alterations in microbiota composition — including an increase in bacteria that produce pro-inflammatory flagellin — and development of chronic inflammation.
Wild-type mice treated with these compounds developed metabolic disease, and mice that were modified to be predisposed to colitis had a higher incidence of robust colitis. Moreover, fecal transplantation from emulsifier-treated mice to germ-free mice reproduced these changes, “clearly suggesting that the microbiome itself is sufficient to drive chronic inflammation,” he said.
In recent years, in humans, analyses from the large French NutriNet-Sante prospective cohort study have shown associations between exposure to food additive emulsifiers and the risk for cardiovascular disease, the risk for cancer (overall, breast, and prostate), and the risk for type 2 diabetes.
But to explore causality and better understand the mechanisms of emulsifier-driven changes on the microbiota, Chassaing and his colleagues also launched the FRESH study (Functional Research on Emulsifier in Humans), a double-blind randomized controlled-feeding study of the emulsifier CMC. For 11 days, nine healthy patients consumed an emulsifier-free diet and 11 consumed an identical diet enriched with 15 g/d of CMC.
Patients on the CMC-containing diet had reduced microbiota diversity and depletions of an array of microbiota-related metabolites, but only a small subset had profound alterations in microbiota composition and increased microbiota encroachment into the mucus layer. “Some seemed to be resistant to CMC-induced microbiota encroachment, while some were highly susceptible,” Chassaing said.
The pilot study raised the question, he said, of whether there is an “infectivity component” — some kind of “sensitive” gut microbiota composition — that may be associated with dietary emulsifier-driven inflammation and disease.
In other murine research, Chassaing and his team found that germ-free mice colonized with Crohn’s disease-associated adherent-invasive E coli (AIEC) and subsequently given CMC or P80 developed chronic inflammation and metabolic dysregulation, “clearly demonstrating that you can convert resistant mice to sensitive mice just by adding one bacteria to the ecosystem,” he said. “The presence of AIEC alone was sufficient to drive the detrimental effects of dietary emulsifiers.”
(In vitro research with transcriptomic analysis then showed that the emulsifiers directly elicit AIEC virulence gene expression, Chassaing and his coauthors wrote in their 2020 paper, facilitating AIEC’s “penetration of the mucus layer and adherence to epithelial cells and resulting in activation of host pro-inflammatory signaling.”)
“We don’t think it’s solely the AIEC bacteria that will drive emulsifier sensitivity, though…we think it’s more complex,” Chassaing said at the meeting. Overall, the findings raise the question of whether emulsifier-sensitive individuals can be identified.
This, he said, is one of his most recent research questions. His lab has led the development of an in vitro microbiota model built to predict an individual’s sensitivity to emulsifiers. In a study published in April, the model recapitulated the differential CMC sensitivity observed in the earlier FRESH study, suggesting that an individual’s sensitivity to emulsifiers can indeed be predicted by examining their baseline microbiota.
Interpreting the Epidemiology
Chassaing’s research arch illustrates the synergy between epidemiological research, basic/translational research, and clinical interventional research that’s needed to understand the diet-microbiome intersection in inflammatory bowel disease, said Ashwin Ananthakrishnan, MBBS, MPH, AGAF, associate professor of medicine at Massachusetts General Hospital, Boston, in an interview at the meeting.
“It’s a good example of how to really span the spectrum, starting from the big picture and going deeper to understand mechanisms, and starting from mechanisms and expanding it out,” Ananthakrishnan said.
In his own talk about research on IBD, Ananthakrishnan said that epidemiological data have shown over the past 10-15 years that total dietary fiber is inversely associated with the risk for Crohn’s disease (with the strongest associations with fiber from fruits and vegetables). Studies have also shown that a higher intake of polyunsaturated fatty acids is associated with a lower risk for ulcerative colitis, whereas “an n-6-fatty acid-rich diet is associated with a higher risk of ulcerative colitis,” he said.
Dietary cohort studies, meanwhile, have shed light on the influence of dietary patterns — such as the Mediterranean diet and diets with high inflammatory potential—on IBD. A diet rich in ultra-processed foods has also been shown in a prospective cohort study to be associated with a higher risk for Crohn’s disease, with certain categories of ultra-processed foods (eg, breads and breakfast foods) having the strongest associations.
Such studies are limited in part, however, by inadequate assessment of potentially relevant variables such as emulsifiers, preservatives, and how the food is processed, he said.
And in interpreting the epidemiological research on fiber and IBD, for instance, one must appreciate that “there are a number of mechanisms by which fiber is impactful…there’s a big picture to look at,” Ananthakrishnan said. Fiber “can affect the microbiome, clearly, it can affect the gut barrier, and it can affect bile acids, and there are detailed translational studies in support of each of these.”
But there are other constituents of fruits and vegetables “that could potentially influence disease risk, such as AhR ligands and polyphenols,” he said. “And importantly, people not eating a lot of fiber may be eating a lot of ultra-processed foods.”
Most interventional studies of fiber have not shown a benefit of a high-fiber diet, Ananthakrishnan said, but there are multiple possible reasons and factors at play, including potential population differences (eg, in inflammatory status or baseline microbiota), shortcomings of the interventions, and potentially inaccurate outcomes.
Abigail Johnson, PhD, RDN, associate director of the Nutrition Coordinating Center, University of Minnesota Twin Cities, which supports dietary analysis, said during the session that the focus of dietary research is “moving toward understanding overall dietary patterns” as opposed to focusing more narrowly on vitamins, minerals, and macronutrients such as proteins, fats, and carbohydrates.
This is an improvement, though “we still don’t have good approaches for understanding [the contributions of] things like additives and emulsifiers, food preparation and cooking, and food processing,” said Johnson, assistant professor in the Division of Epidemiology and Community Health at University of Minnesota Twin Cities. “Perhaps by looking at things at the food level we can overcome some of these limitations.”
Ananthakrishnan reported being a consultant for Geneoscopy and receiving a research grant from Takeda. Chassaing did not report any financial disclosures. Johnson reported that she had no financial disclosures.
A version of this article appeared on Medscape.com.
WASHINGTON, DC — involving 154 patients with mildly active disease living across the United Kingdom.
The findings were reported at Gut Microbiota for Health (GMFH) World Summit 2025 by Benoit Chassaing, PhD, of the Institut Pasteur, Paris, France, whose research leading up to the trial has demonstrated that food additive emulsifiers —ubiquitous in processed foods — alter microbiota composition and lead to microbiota encroachment into the mucus layer of the gut and subsequent chronic gut inflammation.
Patients in the ADDapt trial, which was also reported in an abstract earlier this year at the European Crohn’s and Colitis Organization (ECCO) 2025 Congress, had a Crohn’s disease activity index (CDAI) of 150-250 and evidence of inflammation (faecal calprotectin (FCP) ≥ 150 µg/g or endoscopy/radiology). All “had been exposed in their regular diets to emulsifiers,” said Chassaing, a co-investigator, during a GMFH session on “Dietary Drivers of Health and Disease.”
They were randomized to either a low-emulsifier diet or to a low-emulsifier diet followed by emulsifier “resupplementation” — a design meant to “account for the very strong placebo effect that is always observed with dietary studies,” he said.
All patients received dietary counseling, a smart phone app and barcode scan to support shopping, and weekly support. They also received supermarket foods for 25% of their needs that were either free of emulsifiers or contained emulsifiers, and they were provided three snacks per day that were emulsifier-free or contained carrageenan, carboxymethycellulse (CMC), and polysorbate-80 (P80) — dietary emulsifiers that are commonly added to processed foods to enhance texture and extend shelf-life.
In the intention-to-treat (ITT) analysis, 49% of patients in the intervention group reached the primary endpoint of a 70-point reduction or more in CDAI response after 8 weeks compared with 31% of those in the control group (P = .019), with an adjusted relative risk of response of 3.1 (P = .003), Chassaing shared at the GMFH meeting, convened by the American Gastroenterological Association and the European Society of Neurogastroenterology and Motility.
In the per-protocol analysis (n = 119), 61% and 47% of patients in the intervention and control groups, respectively, reached the primary outcome of CDAI response, with an adjusted relative risk of response of 3.0 (P = .018), he said.
Secondary endpoints included CDAI remission at 24 weeks, and according to the abstract for the ECCO Congress, in the ITT analysis, patients in the intervention group were more than twice as likely to experience remission.
Chassaing noted at the GMFH meeting that as part of the study, he and coinvestigators have been investigating the participants’ gut microbiota with metagenomic analyses. The study was led by Kevin Whelan, PhD, head of the Department of Nutritional Sciences at King’s College London, London, England.
Can Emulsifier-Sensitive Individuals Be Identified?
In murine model research 10 years ago, Chassaing showed that the administration of CMC and P80 results in microbiota encroachment into the mucus layer of the gut, alterations in microbiota composition — including an increase in bacteria that produce pro-inflammatory flagellin — and development of chronic inflammation.
Wild-type mice treated with these compounds developed metabolic disease, and mice that were modified to be predisposed to colitis had a higher incidence of robust colitis. Moreover, fecal transplantation from emulsifier-treated mice to germ-free mice reproduced these changes, “clearly suggesting that the microbiome itself is sufficient to drive chronic inflammation,” he said.
In recent years, in humans, analyses from the large French NutriNet-Sante prospective cohort study have shown associations between exposure to food additive emulsifiers and the risk for cardiovascular disease, the risk for cancer (overall, breast, and prostate), and the risk for type 2 diabetes.
But to explore causality and better understand the mechanisms of emulsifier-driven changes on the microbiota, Chassaing and his colleagues also launched the FRESH study (Functional Research on Emulsifier in Humans), a double-blind randomized controlled-feeding study of the emulsifier CMC. For 11 days, nine healthy patients consumed an emulsifier-free diet and 11 consumed an identical diet enriched with 15 g/d of CMC.
Patients on the CMC-containing diet had reduced microbiota diversity and depletions of an array of microbiota-related metabolites, but only a small subset had profound alterations in microbiota composition and increased microbiota encroachment into the mucus layer. “Some seemed to be resistant to CMC-induced microbiota encroachment, while some were highly susceptible,” Chassaing said.
The pilot study raised the question, he said, of whether there is an “infectivity component” — some kind of “sensitive” gut microbiota composition — that may be associated with dietary emulsifier-driven inflammation and disease.
In other murine research, Chassaing and his team found that germ-free mice colonized with Crohn’s disease-associated adherent-invasive E coli (AIEC) and subsequently given CMC or P80 developed chronic inflammation and metabolic dysregulation, “clearly demonstrating that you can convert resistant mice to sensitive mice just by adding one bacteria to the ecosystem,” he said. “The presence of AIEC alone was sufficient to drive the detrimental effects of dietary emulsifiers.”
(In vitro research with transcriptomic analysis then showed that the emulsifiers directly elicit AIEC virulence gene expression, Chassaing and his coauthors wrote in their 2020 paper, facilitating AIEC’s “penetration of the mucus layer and adherence to epithelial cells and resulting in activation of host pro-inflammatory signaling.”)
“We don’t think it’s solely the AIEC bacteria that will drive emulsifier sensitivity, though…we think it’s more complex,” Chassaing said at the meeting. Overall, the findings raise the question of whether emulsifier-sensitive individuals can be identified.
This, he said, is one of his most recent research questions. His lab has led the development of an in vitro microbiota model built to predict an individual’s sensitivity to emulsifiers. In a study published in April, the model recapitulated the differential CMC sensitivity observed in the earlier FRESH study, suggesting that an individual’s sensitivity to emulsifiers can indeed be predicted by examining their baseline microbiota.
Interpreting the Epidemiology
Chassaing’s research arch illustrates the synergy between epidemiological research, basic/translational research, and clinical interventional research that’s needed to understand the diet-microbiome intersection in inflammatory bowel disease, said Ashwin Ananthakrishnan, MBBS, MPH, AGAF, associate professor of medicine at Massachusetts General Hospital, Boston, in an interview at the meeting.
“It’s a good example of how to really span the spectrum, starting from the big picture and going deeper to understand mechanisms, and starting from mechanisms and expanding it out,” Ananthakrishnan said.
In his own talk about research on IBD, Ananthakrishnan said that epidemiological data have shown over the past 10-15 years that total dietary fiber is inversely associated with the risk for Crohn’s disease (with the strongest associations with fiber from fruits and vegetables). Studies have also shown that a higher intake of polyunsaturated fatty acids is associated with a lower risk for ulcerative colitis, whereas “an n-6-fatty acid-rich diet is associated with a higher risk of ulcerative colitis,” he said.
Dietary cohort studies, meanwhile, have shed light on the influence of dietary patterns — such as the Mediterranean diet and diets with high inflammatory potential—on IBD. A diet rich in ultra-processed foods has also been shown in a prospective cohort study to be associated with a higher risk for Crohn’s disease, with certain categories of ultra-processed foods (eg, breads and breakfast foods) having the strongest associations.
Such studies are limited in part, however, by inadequate assessment of potentially relevant variables such as emulsifiers, preservatives, and how the food is processed, he said.
And in interpreting the epidemiological research on fiber and IBD, for instance, one must appreciate that “there are a number of mechanisms by which fiber is impactful…there’s a big picture to look at,” Ananthakrishnan said. Fiber “can affect the microbiome, clearly, it can affect the gut barrier, and it can affect bile acids, and there are detailed translational studies in support of each of these.”
But there are other constituents of fruits and vegetables “that could potentially influence disease risk, such as AhR ligands and polyphenols,” he said. “And importantly, people not eating a lot of fiber may be eating a lot of ultra-processed foods.”
Most interventional studies of fiber have not shown a benefit of a high-fiber diet, Ananthakrishnan said, but there are multiple possible reasons and factors at play, including potential population differences (eg, in inflammatory status or baseline microbiota), shortcomings of the interventions, and potentially inaccurate outcomes.
Abigail Johnson, PhD, RDN, associate director of the Nutrition Coordinating Center, University of Minnesota Twin Cities, which supports dietary analysis, said during the session that the focus of dietary research is “moving toward understanding overall dietary patterns” as opposed to focusing more narrowly on vitamins, minerals, and macronutrients such as proteins, fats, and carbohydrates.
This is an improvement, though “we still don’t have good approaches for understanding [the contributions of] things like additives and emulsifiers, food preparation and cooking, and food processing,” said Johnson, assistant professor in the Division of Epidemiology and Community Health at University of Minnesota Twin Cities. “Perhaps by looking at things at the food level we can overcome some of these limitations.”
Ananthakrishnan reported being a consultant for Geneoscopy and receiving a research grant from Takeda. Chassaing did not report any financial disclosures. Johnson reported that she had no financial disclosures.
A version of this article appeared on Medscape.com.
WASHINGTON, DC — involving 154 patients with mildly active disease living across the United Kingdom.
The findings were reported at Gut Microbiota for Health (GMFH) World Summit 2025 by Benoit Chassaing, PhD, of the Institut Pasteur, Paris, France, whose research leading up to the trial has demonstrated that food additive emulsifiers —ubiquitous in processed foods — alter microbiota composition and lead to microbiota encroachment into the mucus layer of the gut and subsequent chronic gut inflammation.
Patients in the ADDapt trial, which was also reported in an abstract earlier this year at the European Crohn’s and Colitis Organization (ECCO) 2025 Congress, had a Crohn’s disease activity index (CDAI) of 150-250 and evidence of inflammation (faecal calprotectin (FCP) ≥ 150 µg/g or endoscopy/radiology). All “had been exposed in their regular diets to emulsifiers,” said Chassaing, a co-investigator, during a GMFH session on “Dietary Drivers of Health and Disease.”
They were randomized to either a low-emulsifier diet or to a low-emulsifier diet followed by emulsifier “resupplementation” — a design meant to “account for the very strong placebo effect that is always observed with dietary studies,” he said.
All patients received dietary counseling, a smart phone app and barcode scan to support shopping, and weekly support. They also received supermarket foods for 25% of their needs that were either free of emulsifiers or contained emulsifiers, and they were provided three snacks per day that were emulsifier-free or contained carrageenan, carboxymethycellulse (CMC), and polysorbate-80 (P80) — dietary emulsifiers that are commonly added to processed foods to enhance texture and extend shelf-life.
In the intention-to-treat (ITT) analysis, 49% of patients in the intervention group reached the primary endpoint of a 70-point reduction or more in CDAI response after 8 weeks compared with 31% of those in the control group (P = .019), with an adjusted relative risk of response of 3.1 (P = .003), Chassaing shared at the GMFH meeting, convened by the American Gastroenterological Association and the European Society of Neurogastroenterology and Motility.
In the per-protocol analysis (n = 119), 61% and 47% of patients in the intervention and control groups, respectively, reached the primary outcome of CDAI response, with an adjusted relative risk of response of 3.0 (P = .018), he said.
Secondary endpoints included CDAI remission at 24 weeks, and according to the abstract for the ECCO Congress, in the ITT analysis, patients in the intervention group were more than twice as likely to experience remission.
Chassaing noted at the GMFH meeting that as part of the study, he and coinvestigators have been investigating the participants’ gut microbiota with metagenomic analyses. The study was led by Kevin Whelan, PhD, head of the Department of Nutritional Sciences at King’s College London, London, England.
Can Emulsifier-Sensitive Individuals Be Identified?
In murine model research 10 years ago, Chassaing showed that the administration of CMC and P80 results in microbiota encroachment into the mucus layer of the gut, alterations in microbiota composition — including an increase in bacteria that produce pro-inflammatory flagellin — and development of chronic inflammation.
Wild-type mice treated with these compounds developed metabolic disease, and mice that were modified to be predisposed to colitis had a higher incidence of robust colitis. Moreover, fecal transplantation from emulsifier-treated mice to germ-free mice reproduced these changes, “clearly suggesting that the microbiome itself is sufficient to drive chronic inflammation,” he said.
In recent years, in humans, analyses from the large French NutriNet-Sante prospective cohort study have shown associations between exposure to food additive emulsifiers and the risk for cardiovascular disease, the risk for cancer (overall, breast, and prostate), and the risk for type 2 diabetes.
But to explore causality and better understand the mechanisms of emulsifier-driven changes on the microbiota, Chassaing and his colleagues also launched the FRESH study (Functional Research on Emulsifier in Humans), a double-blind randomized controlled-feeding study of the emulsifier CMC. For 11 days, nine healthy patients consumed an emulsifier-free diet and 11 consumed an identical diet enriched with 15 g/d of CMC.
Patients on the CMC-containing diet had reduced microbiota diversity and depletions of an array of microbiota-related metabolites, but only a small subset had profound alterations in microbiota composition and increased microbiota encroachment into the mucus layer. “Some seemed to be resistant to CMC-induced microbiota encroachment, while some were highly susceptible,” Chassaing said.
The pilot study raised the question, he said, of whether there is an “infectivity component” — some kind of “sensitive” gut microbiota composition — that may be associated with dietary emulsifier-driven inflammation and disease.
In other murine research, Chassaing and his team found that germ-free mice colonized with Crohn’s disease-associated adherent-invasive E coli (AIEC) and subsequently given CMC or P80 developed chronic inflammation and metabolic dysregulation, “clearly demonstrating that you can convert resistant mice to sensitive mice just by adding one bacteria to the ecosystem,” he said. “The presence of AIEC alone was sufficient to drive the detrimental effects of dietary emulsifiers.”
(In vitro research with transcriptomic analysis then showed that the emulsifiers directly elicit AIEC virulence gene expression, Chassaing and his coauthors wrote in their 2020 paper, facilitating AIEC’s “penetration of the mucus layer and adherence to epithelial cells and resulting in activation of host pro-inflammatory signaling.”)
“We don’t think it’s solely the AIEC bacteria that will drive emulsifier sensitivity, though…we think it’s more complex,” Chassaing said at the meeting. Overall, the findings raise the question of whether emulsifier-sensitive individuals can be identified.
This, he said, is one of his most recent research questions. His lab has led the development of an in vitro microbiota model built to predict an individual’s sensitivity to emulsifiers. In a study published in April, the model recapitulated the differential CMC sensitivity observed in the earlier FRESH study, suggesting that an individual’s sensitivity to emulsifiers can indeed be predicted by examining their baseline microbiota.
Interpreting the Epidemiology
Chassaing’s research arch illustrates the synergy between epidemiological research, basic/translational research, and clinical interventional research that’s needed to understand the diet-microbiome intersection in inflammatory bowel disease, said Ashwin Ananthakrishnan, MBBS, MPH, AGAF, associate professor of medicine at Massachusetts General Hospital, Boston, in an interview at the meeting.
“It’s a good example of how to really span the spectrum, starting from the big picture and going deeper to understand mechanisms, and starting from mechanisms and expanding it out,” Ananthakrishnan said.
In his own talk about research on IBD, Ananthakrishnan said that epidemiological data have shown over the past 10-15 years that total dietary fiber is inversely associated with the risk for Crohn’s disease (with the strongest associations with fiber from fruits and vegetables). Studies have also shown that a higher intake of polyunsaturated fatty acids is associated with a lower risk for ulcerative colitis, whereas “an n-6-fatty acid-rich diet is associated with a higher risk of ulcerative colitis,” he said.
Dietary cohort studies, meanwhile, have shed light on the influence of dietary patterns — such as the Mediterranean diet and diets with high inflammatory potential—on IBD. A diet rich in ultra-processed foods has also been shown in a prospective cohort study to be associated with a higher risk for Crohn’s disease, with certain categories of ultra-processed foods (eg, breads and breakfast foods) having the strongest associations.
Such studies are limited in part, however, by inadequate assessment of potentially relevant variables such as emulsifiers, preservatives, and how the food is processed, he said.
And in interpreting the epidemiological research on fiber and IBD, for instance, one must appreciate that “there are a number of mechanisms by which fiber is impactful…there’s a big picture to look at,” Ananthakrishnan said. Fiber “can affect the microbiome, clearly, it can affect the gut barrier, and it can affect bile acids, and there are detailed translational studies in support of each of these.”
But there are other constituents of fruits and vegetables “that could potentially influence disease risk, such as AhR ligands and polyphenols,” he said. “And importantly, people not eating a lot of fiber may be eating a lot of ultra-processed foods.”
Most interventional studies of fiber have not shown a benefit of a high-fiber diet, Ananthakrishnan said, but there are multiple possible reasons and factors at play, including potential population differences (eg, in inflammatory status or baseline microbiota), shortcomings of the interventions, and potentially inaccurate outcomes.
Abigail Johnson, PhD, RDN, associate director of the Nutrition Coordinating Center, University of Minnesota Twin Cities, which supports dietary analysis, said during the session that the focus of dietary research is “moving toward understanding overall dietary patterns” as opposed to focusing more narrowly on vitamins, minerals, and macronutrients such as proteins, fats, and carbohydrates.
This is an improvement, though “we still don’t have good approaches for understanding [the contributions of] things like additives and emulsifiers, food preparation and cooking, and food processing,” said Johnson, assistant professor in the Division of Epidemiology and Community Health at University of Minnesota Twin Cities. “Perhaps by looking at things at the food level we can overcome some of these limitations.”
Ananthakrishnan reported being a consultant for Geneoscopy and receiving a research grant from Takeda. Chassaing did not report any financial disclosures. Johnson reported that she had no financial disclosures.
A version of this article appeared on Medscape.com.
FROM GMFH 2025
Does Tofacitinib Worsen Postoperative Complications in Acute Severe Ulcerative Colitis?
A head-to-head comparison of the JAK inhibitor drug tofacitinib and chimeric monoclonal antibody infliximab in the treatment of acute severe ulcerative colitis (ASUC) shows that, contrary to concerns, tofacitinib is not associated with worse postoperative complications and in fact may reduce the risk of the need for colectomy.
“Tofacitinib has shown efficacy in managing ASUC, but concerns about postoperative complications have limited its adoption,” reported the authors in research published in Clinical Gastroenterology and Hepatology.“, which is unfortunately common in this population,” senior author Jeffrey A. Berinstein, MD, of the Division of Gastroenterology and Hepatology, Michigan Medicine, Ann Arbor, Michigan, told GI & Hepatology News.
Recent treatment advances for UC have provided significant benefits in reducing the severity of symptoms; however, about a quarter of patients go on to experience flares, with fecal urgency, rectal bleeding, and severe abdominal pain of ASUC potentially requiring hospitalization.
The standard of care for those patients is rapid induction with intravenous (IV) corticosteroids; however, up to 30% of patients don’t respond to those interventions, and even with subsequent treatment of cyclosporine and infliximab helping to reduce the risk for an urgent colectomy, patients often don’t respond, and ultimately, up to a third of patients with ASUC end up having to receive a colectomy.
While JAK inhibitor therapies, including tofacitinib and upadacitinib, have recently emerged as potentially important treatment options in such cases, showing reductions in the risk for colectomy, concerns about the drugs’ downstream biologic effects have given many clinicians reservations about their use.
“Anecdotally, gastroenterologists and surgeons have expressed concern about JAK inhibitors leading to poor wound healing, as well as increasing both intraoperative and postoperative complications, despite limited data to support these claims,” the authors wrote.
To better understand those possible risks, first author Charlotte Larson, MD, of the Department of Internal Medicine, Michigan Medicine, and colleagues conducted a multicenter, retrospective, case-control study of 109 patients hospitalized with ASUC at two centers in the US and 14 in France.
Of the patients, 41 were treated with tofacitinib and 68 with infliximab prior to colectomy.
Among patients treated with tofacitinib, five (12.2%) received infliximab and four (9.8%) received cyclosporine rescue immediately prior to receiving tofacitinib during the index admission. In the infliximab group, one (1.5%) received rescue cyclosporine.
In a univariate analysis, the tofacitinib-treated patients showed significantly lower overall rates of postoperative complications than infliximab-treated patients (31.7% vs 64.7%; odds ratio [OR], 0.33; P = .006).
The tofacitinib-treated group also had lower rates of serious postoperative complications (12% vs 28.9; OR, 0.20; P = .016).
After adjusting for multivariate factors including age, inflammatory burden, nutrition status, 90-day cumulative corticosteroid exposure and open surgery, there was a trend favoring tofacitinib but no statistically significant difference between the two treatments in terms of serious postoperative complications (P = .061).
However, a significantly lower rate of overall postoperative complications with tofacitinib was observed after the adjustment (odds ratio, 0.38; P = .023).
Importantly, a subanalysis showed that the 63.4% of tofacitinib-treated patients receiving the standard FDA-approved induction dose of 10 mg twice daily did indeed have significantly lower rates than infliximab-treated patients in terms of serious postoperative complications (OR, .10; P = .031), as well as overall postoperative complications (OR, 0.23; P = .003), whereas neither of the outcomes were significantly improved among the 36.6% of patients who received the higher-intensity thrice-daily tofacitinib dose (P = .3 and P = .4, respectively).
Further complicating the matter, in a previous case-control study that the research team conducted, it was the off-label, 10 mg thrice-daily dose of tofacitinib that performed favorably and was associated with a significantly lower risk for colectomy than the twice-daily dose (hazard ratio 0.28; P = .018); the twice-daily dose was not protective.
Berinstein added that a hypothesis for the benefits overall, with either dose, is that tofacitinib’s anti-inflammatory properties are key.
“We believe that lowering inflammation as much as possible, with the colon less inflamed, could be providing the benefit in lowering complications rate in surgery,” he explained.
Regarding the dosing, “it’s a careful trade-off,” Berinstein added. “Obviously, we want to avoid the need for a colectomy in the first place, as it is a life-changing surgery, but we don’t want to increase the risk of infections.”
In other findings, the tofacitinib group had no increased risk for postoperative venous thrombotic embolisms (VTEs), which is important as tofacitinib exposure has previously been associated with an increased risk for VTEs independent of other prothrombotic factors common to patients with ASUC, including decreased ambulation, active inflammation, corticosteroid use, and major colorectal surgery.
“This observed absence of an increased VTE risk may alleviate some of the hypothetical postoperative safety concern attributed to JAK inhibitor therapy in this high-risk population,” the authors wrote.
Overall, the results underscore that “providers should feel comfortable using this medication if they need it and if they think it’s most likely to help their patients avoid colectomy,” Berinstein said.
“They should not give pause over concerns of postoperative complications because we didn’t show that,” he said.
Commenting on the study, Joseph D. Feuerstein, MD, AGAF, of the Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, noted that, in general, in patients with ASUC who fail on IV steroids, “the main treatments are infliximab, cyclosporine, or a JAK inhibitor like tofacitinib or upadacitinib, [and] knowing that if someone needs surgery, the complication rates are similar and that pre-operative use is okay is reassuring.”
Regarding the protective effect observed with some circumstances, “I don’t put too much weight into that,” he noted. “[One] could speculate that it is somehow related to faster half-life of the drug, and it might not sit around as long,” he said.
Feuerstein added that “the study design being retrospective is a limitation, but this is the best data we have to date.”
Berinstein and Feuerstein had no disclosures to report.
A version of this article appeared on Medscape.com .
A head-to-head comparison of the JAK inhibitor drug tofacitinib and chimeric monoclonal antibody infliximab in the treatment of acute severe ulcerative colitis (ASUC) shows that, contrary to concerns, tofacitinib is not associated with worse postoperative complications and in fact may reduce the risk of the need for colectomy.
“Tofacitinib has shown efficacy in managing ASUC, but concerns about postoperative complications have limited its adoption,” reported the authors in research published in Clinical Gastroenterology and Hepatology.“, which is unfortunately common in this population,” senior author Jeffrey A. Berinstein, MD, of the Division of Gastroenterology and Hepatology, Michigan Medicine, Ann Arbor, Michigan, told GI & Hepatology News.
Recent treatment advances for UC have provided significant benefits in reducing the severity of symptoms; however, about a quarter of patients go on to experience flares, with fecal urgency, rectal bleeding, and severe abdominal pain of ASUC potentially requiring hospitalization.
The standard of care for those patients is rapid induction with intravenous (IV) corticosteroids; however, up to 30% of patients don’t respond to those interventions, and even with subsequent treatment of cyclosporine and infliximab helping to reduce the risk for an urgent colectomy, patients often don’t respond, and ultimately, up to a third of patients with ASUC end up having to receive a colectomy.
While JAK inhibitor therapies, including tofacitinib and upadacitinib, have recently emerged as potentially important treatment options in such cases, showing reductions in the risk for colectomy, concerns about the drugs’ downstream biologic effects have given many clinicians reservations about their use.
“Anecdotally, gastroenterologists and surgeons have expressed concern about JAK inhibitors leading to poor wound healing, as well as increasing both intraoperative and postoperative complications, despite limited data to support these claims,” the authors wrote.
To better understand those possible risks, first author Charlotte Larson, MD, of the Department of Internal Medicine, Michigan Medicine, and colleagues conducted a multicenter, retrospective, case-control study of 109 patients hospitalized with ASUC at two centers in the US and 14 in France.
Of the patients, 41 were treated with tofacitinib and 68 with infliximab prior to colectomy.
Among patients treated with tofacitinib, five (12.2%) received infliximab and four (9.8%) received cyclosporine rescue immediately prior to receiving tofacitinib during the index admission. In the infliximab group, one (1.5%) received rescue cyclosporine.
In a univariate analysis, the tofacitinib-treated patients showed significantly lower overall rates of postoperative complications than infliximab-treated patients (31.7% vs 64.7%; odds ratio [OR], 0.33; P = .006).
The tofacitinib-treated group also had lower rates of serious postoperative complications (12% vs 28.9; OR, 0.20; P = .016).
After adjusting for multivariate factors including age, inflammatory burden, nutrition status, 90-day cumulative corticosteroid exposure and open surgery, there was a trend favoring tofacitinib but no statistically significant difference between the two treatments in terms of serious postoperative complications (P = .061).
However, a significantly lower rate of overall postoperative complications with tofacitinib was observed after the adjustment (odds ratio, 0.38; P = .023).
Importantly, a subanalysis showed that the 63.4% of tofacitinib-treated patients receiving the standard FDA-approved induction dose of 10 mg twice daily did indeed have significantly lower rates than infliximab-treated patients in terms of serious postoperative complications (OR, .10; P = .031), as well as overall postoperative complications (OR, 0.23; P = .003), whereas neither of the outcomes were significantly improved among the 36.6% of patients who received the higher-intensity thrice-daily tofacitinib dose (P = .3 and P = .4, respectively).
Further complicating the matter, in a previous case-control study that the research team conducted, it was the off-label, 10 mg thrice-daily dose of tofacitinib that performed favorably and was associated with a significantly lower risk for colectomy than the twice-daily dose (hazard ratio 0.28; P = .018); the twice-daily dose was not protective.
Berinstein added that a hypothesis for the benefits overall, with either dose, is that tofacitinib’s anti-inflammatory properties are key.
“We believe that lowering inflammation as much as possible, with the colon less inflamed, could be providing the benefit in lowering complications rate in surgery,” he explained.
Regarding the dosing, “it’s a careful trade-off,” Berinstein added. “Obviously, we want to avoid the need for a colectomy in the first place, as it is a life-changing surgery, but we don’t want to increase the risk of infections.”
In other findings, the tofacitinib group had no increased risk for postoperative venous thrombotic embolisms (VTEs), which is important as tofacitinib exposure has previously been associated with an increased risk for VTEs independent of other prothrombotic factors common to patients with ASUC, including decreased ambulation, active inflammation, corticosteroid use, and major colorectal surgery.
“This observed absence of an increased VTE risk may alleviate some of the hypothetical postoperative safety concern attributed to JAK inhibitor therapy in this high-risk population,” the authors wrote.
Overall, the results underscore that “providers should feel comfortable using this medication if they need it and if they think it’s most likely to help their patients avoid colectomy,” Berinstein said.
“They should not give pause over concerns of postoperative complications because we didn’t show that,” he said.
Commenting on the study, Joseph D. Feuerstein, MD, AGAF, of the Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, noted that, in general, in patients with ASUC who fail on IV steroids, “the main treatments are infliximab, cyclosporine, or a JAK inhibitor like tofacitinib or upadacitinib, [and] knowing that if someone needs surgery, the complication rates are similar and that pre-operative use is okay is reassuring.”
Regarding the protective effect observed with some circumstances, “I don’t put too much weight into that,” he noted. “[One] could speculate that it is somehow related to faster half-life of the drug, and it might not sit around as long,” he said.
Feuerstein added that “the study design being retrospective is a limitation, but this is the best data we have to date.”
Berinstein and Feuerstein had no disclosures to report.
A version of this article appeared on Medscape.com .
A head-to-head comparison of the JAK inhibitor drug tofacitinib and chimeric monoclonal antibody infliximab in the treatment of acute severe ulcerative colitis (ASUC) shows that, contrary to concerns, tofacitinib is not associated with worse postoperative complications and in fact may reduce the risk of the need for colectomy.
“Tofacitinib has shown efficacy in managing ASUC, but concerns about postoperative complications have limited its adoption,” reported the authors in research published in Clinical Gastroenterology and Hepatology.“, which is unfortunately common in this population,” senior author Jeffrey A. Berinstein, MD, of the Division of Gastroenterology and Hepatology, Michigan Medicine, Ann Arbor, Michigan, told GI & Hepatology News.
Recent treatment advances for UC have provided significant benefits in reducing the severity of symptoms; however, about a quarter of patients go on to experience flares, with fecal urgency, rectal bleeding, and severe abdominal pain of ASUC potentially requiring hospitalization.
The standard of care for those patients is rapid induction with intravenous (IV) corticosteroids; however, up to 30% of patients don’t respond to those interventions, and even with subsequent treatment of cyclosporine and infliximab helping to reduce the risk for an urgent colectomy, patients often don’t respond, and ultimately, up to a third of patients with ASUC end up having to receive a colectomy.
While JAK inhibitor therapies, including tofacitinib and upadacitinib, have recently emerged as potentially important treatment options in such cases, showing reductions in the risk for colectomy, concerns about the drugs’ downstream biologic effects have given many clinicians reservations about their use.
“Anecdotally, gastroenterologists and surgeons have expressed concern about JAK inhibitors leading to poor wound healing, as well as increasing both intraoperative and postoperative complications, despite limited data to support these claims,” the authors wrote.
To better understand those possible risks, first author Charlotte Larson, MD, of the Department of Internal Medicine, Michigan Medicine, and colleagues conducted a multicenter, retrospective, case-control study of 109 patients hospitalized with ASUC at two centers in the US and 14 in France.
Of the patients, 41 were treated with tofacitinib and 68 with infliximab prior to colectomy.
Among patients treated with tofacitinib, five (12.2%) received infliximab and four (9.8%) received cyclosporine rescue immediately prior to receiving tofacitinib during the index admission. In the infliximab group, one (1.5%) received rescue cyclosporine.
In a univariate analysis, the tofacitinib-treated patients showed significantly lower overall rates of postoperative complications than infliximab-treated patients (31.7% vs 64.7%; odds ratio [OR], 0.33; P = .006).
The tofacitinib-treated group also had lower rates of serious postoperative complications (12% vs 28.9; OR, 0.20; P = .016).
After adjusting for multivariate factors including age, inflammatory burden, nutrition status, 90-day cumulative corticosteroid exposure and open surgery, there was a trend favoring tofacitinib but no statistically significant difference between the two treatments in terms of serious postoperative complications (P = .061).
However, a significantly lower rate of overall postoperative complications with tofacitinib was observed after the adjustment (odds ratio, 0.38; P = .023).
Importantly, a subanalysis showed that the 63.4% of tofacitinib-treated patients receiving the standard FDA-approved induction dose of 10 mg twice daily did indeed have significantly lower rates than infliximab-treated patients in terms of serious postoperative complications (OR, .10; P = .031), as well as overall postoperative complications (OR, 0.23; P = .003), whereas neither of the outcomes were significantly improved among the 36.6% of patients who received the higher-intensity thrice-daily tofacitinib dose (P = .3 and P = .4, respectively).
Further complicating the matter, in a previous case-control study that the research team conducted, it was the off-label, 10 mg thrice-daily dose of tofacitinib that performed favorably and was associated with a significantly lower risk for colectomy than the twice-daily dose (hazard ratio 0.28; P = .018); the twice-daily dose was not protective.
Berinstein added that a hypothesis for the benefits overall, with either dose, is that tofacitinib’s anti-inflammatory properties are key.
“We believe that lowering inflammation as much as possible, with the colon less inflamed, could be providing the benefit in lowering complications rate in surgery,” he explained.
Regarding the dosing, “it’s a careful trade-off,” Berinstein added. “Obviously, we want to avoid the need for a colectomy in the first place, as it is a life-changing surgery, but we don’t want to increase the risk of infections.”
In other findings, the tofacitinib group had no increased risk for postoperative venous thrombotic embolisms (VTEs), which is important as tofacitinib exposure has previously been associated with an increased risk for VTEs independent of other prothrombotic factors common to patients with ASUC, including decreased ambulation, active inflammation, corticosteroid use, and major colorectal surgery.
“This observed absence of an increased VTE risk may alleviate some of the hypothetical postoperative safety concern attributed to JAK inhibitor therapy in this high-risk population,” the authors wrote.
Overall, the results underscore that “providers should feel comfortable using this medication if they need it and if they think it’s most likely to help their patients avoid colectomy,” Berinstein said.
“They should not give pause over concerns of postoperative complications because we didn’t show that,” he said.
Commenting on the study, Joseph D. Feuerstein, MD, AGAF, of the Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, noted that, in general, in patients with ASUC who fail on IV steroids, “the main treatments are infliximab, cyclosporine, or a JAK inhibitor like tofacitinib or upadacitinib, [and] knowing that if someone needs surgery, the complication rates are similar and that pre-operative use is okay is reassuring.”
Regarding the protective effect observed with some circumstances, “I don’t put too much weight into that,” he noted. “[One] could speculate that it is somehow related to faster half-life of the drug, and it might not sit around as long,” he said.
Feuerstein added that “the study design being retrospective is a limitation, but this is the best data we have to date.”
Berinstein and Feuerstein had no disclosures to report.
A version of this article appeared on Medscape.com .
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Endoscopic Lifting Agents: AGA Issues New Clinical Practice Update
Published in Clinical Gastroenterology and Hepatology, the commentary reviews available agents and provides clinically relevant commentary on their indications and use — with the caveat that it is not a formal systematic review but rather empirical advice for endoscopists. No formal rating of the quality of evidence or strength of recommendations was performed.
Led by Tobias Zuchelli, MD, a clinical associate professor at Michigan State University and a gastroenterologist at the Henry Ford Health System in Detroit, the expert panel noted that endoscopists are increasingly resecting precancerous lesions and early cancers of the gastrointestinal tract.
“Although new endoscopic procedures have been developed, there had not been much in terms of high-quality guidance on lifting agents,” panelist Amit V. Patel, MD, a professor of medicine at Duke University and director of Endoscopy at Durham Veterans Affairs Medical Center in Durham, North Carolina, told GI & Hepatology News. “With our better understanding and use of techniques, this commentary was timely. It summarizes the available data on the topic and includes our clinical experiences.”
Filling that knowledge gap, the document reviews in detail the timing and methods of agent injection according to procedure type, including the dynamic needle approach, the empirical merits of different agents such as saline (with or without blue contrast) and viscous agents, as well as lift-enhancing assistive devices — for example, the ERBEJET 2 high-pressure water jet, an adjustable hydrosurgical device to facilitate lifting. A chart provides an at-a-glance summary of agents and their pros and cons.
“The feedback from gastroenterologists so far has been quite positive on social media and on GI channels,” Patel said.
Endoscopic resection has evolved from snare polypectomy to endoscopic mucosal resection (EMR) and now, endoscopic submucosal dissection (ESD). The primary benefit of submucosal lifting is the creation of a separating submucosal cushion between the lesion and muscularis propria (MP), which reduces the risk for immediate or delayed perforation of the muscle. Adding a contrast agent also demarcates lesion margins and stains the submucosa, which is fundamental to ESD and allows for assessment of MP injury during EMR.
For decades, homemade solutions were used to lift lesions before removal, with the sentinel agent being normal saline, later mixed with a blue contrast agent, usually indigo carmine or methylene blue. The authors noted that some endoscopists performing ESD start the submucosal injection and incision using a prepackaged viscous solution. “The endoscopist may continue with the viscous fluid or transition to saline or another less expensive solution,” they wrote.
Saline tends to dissipate more quickly than viscous solutions, however. In 2015, the polymer compound SIC-8000 became the first FDA-approved submucosal injection agent. Since then, several other fluids have come on the market, although homemade agents remain available.
Among the update’s recommendations, the fluid selected for EMR should be determined by lesion size, predicted histology, and endoscopist preference. Based on the US Multi-Society Task Force (USMSTF) on Colorectal Cancer, submucosal injection is optional for nonpedunculated colorectal lesions (NPCRLs) of intermediate size (10-19 mm).
Cold snare polypectomy without submucosal injection was later found to be non-inferior to other resection methods utilizing submucosal injection for NPCRLs ≤ 15 mm.
The update noted that the USMSTF considers EMR first-line therapy for most NPCRLs ≥ 20 mm and advocates viscous solutions as preferred, while the use of lifting agents for pedunculated polyps is generally at the discretion of the endoscopist.
For Patel, the main “clinical pearls” in the update are adding a contrast agent to normal saline, using a viscous agent for cold EMR, and manipulating the injection needle first tangentially and then dynamically toward the lumen to maximize separation of the lesion.
In terms of the ideal, an optimal lifting solution would be readily available, inexpensive, and premixed, providing a sustained submucosal cushion. “However, this ideal solution currently does not exist. Injection fluids should, therefore, be selected based on planned resection method, predicted histology, local expertise and preferences, and cost,” the panelists wrote.
Added Patel, “A lot of the agents out there check most of these boxes, but we’re hoping for further development toward the ideal.”
Offering a nonparticipant’s perspective on the overview, Wasseem Skef, MD, a gastroenterologist at UTHealth Houston, found the update very useful. “It always helps to have the literature summarized,” he told GI & Hepatology News. “It’s a pretty balanced review that pulls together the various options but allows people to stick to their preferred practice.”
In his practice, the lifting agent selected depends on the type of resection. “Viscous agents are generally more popular for EMR-type resections,” Skef said. One unanswered question, he noted, is whether adding a hemostatic agent would be superior to a viscous agent alone. “But overall, this is a nice summary of available agents. Gastroenterologists should consider these different options if doing procedures like EMR.”
This review was sponsored by the AGA Institute.
Zuchelli is a consultant for Boston Scientific. Patel consults for Medpace, Renexxion, and Sanofi. Skef reported having no relevant disclosures.
A version of this article appeared on Medscape.com .
Published in Clinical Gastroenterology and Hepatology, the commentary reviews available agents and provides clinically relevant commentary on their indications and use — with the caveat that it is not a formal systematic review but rather empirical advice for endoscopists. No formal rating of the quality of evidence or strength of recommendations was performed.
Led by Tobias Zuchelli, MD, a clinical associate professor at Michigan State University and a gastroenterologist at the Henry Ford Health System in Detroit, the expert panel noted that endoscopists are increasingly resecting precancerous lesions and early cancers of the gastrointestinal tract.
“Although new endoscopic procedures have been developed, there had not been much in terms of high-quality guidance on lifting agents,” panelist Amit V. Patel, MD, a professor of medicine at Duke University and director of Endoscopy at Durham Veterans Affairs Medical Center in Durham, North Carolina, told GI & Hepatology News. “With our better understanding and use of techniques, this commentary was timely. It summarizes the available data on the topic and includes our clinical experiences.”
Filling that knowledge gap, the document reviews in detail the timing and methods of agent injection according to procedure type, including the dynamic needle approach, the empirical merits of different agents such as saline (with or without blue contrast) and viscous agents, as well as lift-enhancing assistive devices — for example, the ERBEJET 2 high-pressure water jet, an adjustable hydrosurgical device to facilitate lifting. A chart provides an at-a-glance summary of agents and their pros and cons.
“The feedback from gastroenterologists so far has been quite positive on social media and on GI channels,” Patel said.
Endoscopic resection has evolved from snare polypectomy to endoscopic mucosal resection (EMR) and now, endoscopic submucosal dissection (ESD). The primary benefit of submucosal lifting is the creation of a separating submucosal cushion between the lesion and muscularis propria (MP), which reduces the risk for immediate or delayed perforation of the muscle. Adding a contrast agent also demarcates lesion margins and stains the submucosa, which is fundamental to ESD and allows for assessment of MP injury during EMR.
For decades, homemade solutions were used to lift lesions before removal, with the sentinel agent being normal saline, later mixed with a blue contrast agent, usually indigo carmine or methylene blue. The authors noted that some endoscopists performing ESD start the submucosal injection and incision using a prepackaged viscous solution. “The endoscopist may continue with the viscous fluid or transition to saline or another less expensive solution,” they wrote.
Saline tends to dissipate more quickly than viscous solutions, however. In 2015, the polymer compound SIC-8000 became the first FDA-approved submucosal injection agent. Since then, several other fluids have come on the market, although homemade agents remain available.
Among the update’s recommendations, the fluid selected for EMR should be determined by lesion size, predicted histology, and endoscopist preference. Based on the US Multi-Society Task Force (USMSTF) on Colorectal Cancer, submucosal injection is optional for nonpedunculated colorectal lesions (NPCRLs) of intermediate size (10-19 mm).
Cold snare polypectomy without submucosal injection was later found to be non-inferior to other resection methods utilizing submucosal injection for NPCRLs ≤ 15 mm.
The update noted that the USMSTF considers EMR first-line therapy for most NPCRLs ≥ 20 mm and advocates viscous solutions as preferred, while the use of lifting agents for pedunculated polyps is generally at the discretion of the endoscopist.
For Patel, the main “clinical pearls” in the update are adding a contrast agent to normal saline, using a viscous agent for cold EMR, and manipulating the injection needle first tangentially and then dynamically toward the lumen to maximize separation of the lesion.
In terms of the ideal, an optimal lifting solution would be readily available, inexpensive, and premixed, providing a sustained submucosal cushion. “However, this ideal solution currently does not exist. Injection fluids should, therefore, be selected based on planned resection method, predicted histology, local expertise and preferences, and cost,” the panelists wrote.
Added Patel, “A lot of the agents out there check most of these boxes, but we’re hoping for further development toward the ideal.”
Offering a nonparticipant’s perspective on the overview, Wasseem Skef, MD, a gastroenterologist at UTHealth Houston, found the update very useful. “It always helps to have the literature summarized,” he told GI & Hepatology News. “It’s a pretty balanced review that pulls together the various options but allows people to stick to their preferred practice.”
In his practice, the lifting agent selected depends on the type of resection. “Viscous agents are generally more popular for EMR-type resections,” Skef said. One unanswered question, he noted, is whether adding a hemostatic agent would be superior to a viscous agent alone. “But overall, this is a nice summary of available agents. Gastroenterologists should consider these different options if doing procedures like EMR.”
This review was sponsored by the AGA Institute.
Zuchelli is a consultant for Boston Scientific. Patel consults for Medpace, Renexxion, and Sanofi. Skef reported having no relevant disclosures.
A version of this article appeared on Medscape.com .
Published in Clinical Gastroenterology and Hepatology, the commentary reviews available agents and provides clinically relevant commentary on their indications and use — with the caveat that it is not a formal systematic review but rather empirical advice for endoscopists. No formal rating of the quality of evidence or strength of recommendations was performed.
Led by Tobias Zuchelli, MD, a clinical associate professor at Michigan State University and a gastroenterologist at the Henry Ford Health System in Detroit, the expert panel noted that endoscopists are increasingly resecting precancerous lesions and early cancers of the gastrointestinal tract.
“Although new endoscopic procedures have been developed, there had not been much in terms of high-quality guidance on lifting agents,” panelist Amit V. Patel, MD, a professor of medicine at Duke University and director of Endoscopy at Durham Veterans Affairs Medical Center in Durham, North Carolina, told GI & Hepatology News. “With our better understanding and use of techniques, this commentary was timely. It summarizes the available data on the topic and includes our clinical experiences.”
Filling that knowledge gap, the document reviews in detail the timing and methods of agent injection according to procedure type, including the dynamic needle approach, the empirical merits of different agents such as saline (with or without blue contrast) and viscous agents, as well as lift-enhancing assistive devices — for example, the ERBEJET 2 high-pressure water jet, an adjustable hydrosurgical device to facilitate lifting. A chart provides an at-a-glance summary of agents and their pros and cons.
“The feedback from gastroenterologists so far has been quite positive on social media and on GI channels,” Patel said.
Endoscopic resection has evolved from snare polypectomy to endoscopic mucosal resection (EMR) and now, endoscopic submucosal dissection (ESD). The primary benefit of submucosal lifting is the creation of a separating submucosal cushion between the lesion and muscularis propria (MP), which reduces the risk for immediate or delayed perforation of the muscle. Adding a contrast agent also demarcates lesion margins and stains the submucosa, which is fundamental to ESD and allows for assessment of MP injury during EMR.
For decades, homemade solutions were used to lift lesions before removal, with the sentinel agent being normal saline, later mixed with a blue contrast agent, usually indigo carmine or methylene blue. The authors noted that some endoscopists performing ESD start the submucosal injection and incision using a prepackaged viscous solution. “The endoscopist may continue with the viscous fluid or transition to saline or another less expensive solution,” they wrote.
Saline tends to dissipate more quickly than viscous solutions, however. In 2015, the polymer compound SIC-8000 became the first FDA-approved submucosal injection agent. Since then, several other fluids have come on the market, although homemade agents remain available.
Among the update’s recommendations, the fluid selected for EMR should be determined by lesion size, predicted histology, and endoscopist preference. Based on the US Multi-Society Task Force (USMSTF) on Colorectal Cancer, submucosal injection is optional for nonpedunculated colorectal lesions (NPCRLs) of intermediate size (10-19 mm).
Cold snare polypectomy without submucosal injection was later found to be non-inferior to other resection methods utilizing submucosal injection for NPCRLs ≤ 15 mm.
The update noted that the USMSTF considers EMR first-line therapy for most NPCRLs ≥ 20 mm and advocates viscous solutions as preferred, while the use of lifting agents for pedunculated polyps is generally at the discretion of the endoscopist.
For Patel, the main “clinical pearls” in the update are adding a contrast agent to normal saline, using a viscous agent for cold EMR, and manipulating the injection needle first tangentially and then dynamically toward the lumen to maximize separation of the lesion.
In terms of the ideal, an optimal lifting solution would be readily available, inexpensive, and premixed, providing a sustained submucosal cushion. “However, this ideal solution currently does not exist. Injection fluids should, therefore, be selected based on planned resection method, predicted histology, local expertise and preferences, and cost,” the panelists wrote.
Added Patel, “A lot of the agents out there check most of these boxes, but we’re hoping for further development toward the ideal.”
Offering a nonparticipant’s perspective on the overview, Wasseem Skef, MD, a gastroenterologist at UTHealth Houston, found the update very useful. “It always helps to have the literature summarized,” he told GI & Hepatology News. “It’s a pretty balanced review that pulls together the various options but allows people to stick to their preferred practice.”
In his practice, the lifting agent selected depends on the type of resection. “Viscous agents are generally more popular for EMR-type resections,” Skef said. One unanswered question, he noted, is whether adding a hemostatic agent would be superior to a viscous agent alone. “But overall, this is a nice summary of available agents. Gastroenterologists should consider these different options if doing procedures like EMR.”
This review was sponsored by the AGA Institute.
Zuchelli is a consultant for Boston Scientific. Patel consults for Medpace, Renexxion, and Sanofi. Skef reported having no relevant disclosures.
A version of this article appeared on Medscape.com .
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
IBS, Chronic Idiopathic Constipation Surged During Pandemic
, with a near doubling of the national rate of IBS over 2 years, a study has found.
The uptick is probably due to not only the direct impact of SARS-CoV-2 infection on the gastrointestinal tract but also to the psychological stress associated with pandemic life, the study team said.
“COVID infection itself can definitely cause gastrointestinal symptoms like diarrhea, nausea, and abdominal pain — and for some people, those symptoms can linger and lead to chronic conditions like IBS,” Christopher V. Almario, MD, MSHPM, lead author and gastroenterologist at Cedars-Sinai Medical Center, Los Angeles, California, told GI & Hepatology News.
“But the stress of living through the pandemic — lockdowns, fear, isolation — also likely played a major role as well in the increased prevalence of digestive disorders. Both the infection itself and the psychological toll of the pandemic can disrupt the gut-brain axis and trigger chronic digestive disorders like IBS,” Almario said.
The study was published in Neurogastroenterology & Motility.
Growing Burden of Gut Disorders
Disorders of gut-brain interaction (DGBIs) are a heterogeneous group of conditions in which gastrointestinal symptoms occur without any detectable structural or biochemical abnormalities in the digestive tract. They include IBS, functional dyspepsia, and chronic idiopathic constipation, among others.
DGBIs are highly prevalent. Research has shown that nearly 40% of people in the US meet Rome IV criteria for at least one DGBI.
Almario and colleagues assessed trends in prevalence of these conditions during the COVID-19 pandemic. Starting in May 2020 through May 2022, they conducted a series of online surveys with more than 160,000 adults aged 18 or older using validated Rome IV diagnostic questionnaires.
Results showed that during the pandemic, IBS prevalence rose from 6.1% in May 2020 to 11.0% by May 2022, an increase of 0.188% per month (adjusted P < .001).
Chronic idiopathic constipation showed a smaller but statistically significant increase, from 6.0% to 6.4% (0.056% per month; adjusted P < .001).
Within the IBS subtypes, mixed-type IBS showed the largest relative increase (0.085% per month), followed by IBS with constipation (0.041% per month) and IBS with diarrhea (0.037% per month).
There were no significant changes in the prevalence of other DGBIs, such as functional bloating, functional diarrhea, or functional dyspepsia, during the study period.
Almario told GI & Hepatology News only about 9% of those surveyed reported a positive COVID test at the time of the surveys, but that figure probably underrepresents actual infections, especially in the early months of the pandemic. “Most of the survey responses came in during the earlier phases of the pandemic, and the percentage reporting a positive test increased over time,” he explained.
Almario also noted that this study did not directly compare digestive disorder rates between infected and uninfected individuals. However, a separate study by the Cedars-Sinai team currently undergoing peer review addresses that question more directly. “That study, along with several other studies, show that having COVID increases the risk of developing conditions like IBS and functional dyspepsia,” Almario said.
Taken together, the findings “underscore the increasing healthcare and economic burden of DGBI in the post-pandemic era, emphasizing the need for targeted efforts to effectively diagnose and manage these complex conditions,” they wrote.
“This will be especially challenging for healthcare systems to address, given the existing shortage of primary care physicians and gastroenterologists — clinicians who primarily manage individuals with DGBI,” they noted.
Support for this study was received from Ironwood Pharmaceuticals and Salix Pharmaceuticals in the form of institutional research grants to Cedars-Sinai. Almario has consulted for Exact Sciences, Greenspace Labs, Owlstone Medical, Salix Pharmaceuticals, and Universal DX.
A version of this article appeared on Medscape.com.
, with a near doubling of the national rate of IBS over 2 years, a study has found.
The uptick is probably due to not only the direct impact of SARS-CoV-2 infection on the gastrointestinal tract but also to the psychological stress associated with pandemic life, the study team said.
“COVID infection itself can definitely cause gastrointestinal symptoms like diarrhea, nausea, and abdominal pain — and for some people, those symptoms can linger and lead to chronic conditions like IBS,” Christopher V. Almario, MD, MSHPM, lead author and gastroenterologist at Cedars-Sinai Medical Center, Los Angeles, California, told GI & Hepatology News.
“But the stress of living through the pandemic — lockdowns, fear, isolation — also likely played a major role as well in the increased prevalence of digestive disorders. Both the infection itself and the psychological toll of the pandemic can disrupt the gut-brain axis and trigger chronic digestive disorders like IBS,” Almario said.
The study was published in Neurogastroenterology & Motility.
Growing Burden of Gut Disorders
Disorders of gut-brain interaction (DGBIs) are a heterogeneous group of conditions in which gastrointestinal symptoms occur without any detectable structural or biochemical abnormalities in the digestive tract. They include IBS, functional dyspepsia, and chronic idiopathic constipation, among others.
DGBIs are highly prevalent. Research has shown that nearly 40% of people in the US meet Rome IV criteria for at least one DGBI.
Almario and colleagues assessed trends in prevalence of these conditions during the COVID-19 pandemic. Starting in May 2020 through May 2022, they conducted a series of online surveys with more than 160,000 adults aged 18 or older using validated Rome IV diagnostic questionnaires.
Results showed that during the pandemic, IBS prevalence rose from 6.1% in May 2020 to 11.0% by May 2022, an increase of 0.188% per month (adjusted P < .001).
Chronic idiopathic constipation showed a smaller but statistically significant increase, from 6.0% to 6.4% (0.056% per month; adjusted P < .001).
Within the IBS subtypes, mixed-type IBS showed the largest relative increase (0.085% per month), followed by IBS with constipation (0.041% per month) and IBS with diarrhea (0.037% per month).
There were no significant changes in the prevalence of other DGBIs, such as functional bloating, functional diarrhea, or functional dyspepsia, during the study period.
Almario told GI & Hepatology News only about 9% of those surveyed reported a positive COVID test at the time of the surveys, but that figure probably underrepresents actual infections, especially in the early months of the pandemic. “Most of the survey responses came in during the earlier phases of the pandemic, and the percentage reporting a positive test increased over time,” he explained.
Almario also noted that this study did not directly compare digestive disorder rates between infected and uninfected individuals. However, a separate study by the Cedars-Sinai team currently undergoing peer review addresses that question more directly. “That study, along with several other studies, show that having COVID increases the risk of developing conditions like IBS and functional dyspepsia,” Almario said.
Taken together, the findings “underscore the increasing healthcare and economic burden of DGBI in the post-pandemic era, emphasizing the need for targeted efforts to effectively diagnose and manage these complex conditions,” they wrote.
“This will be especially challenging for healthcare systems to address, given the existing shortage of primary care physicians and gastroenterologists — clinicians who primarily manage individuals with DGBI,” they noted.
Support for this study was received from Ironwood Pharmaceuticals and Salix Pharmaceuticals in the form of institutional research grants to Cedars-Sinai. Almario has consulted for Exact Sciences, Greenspace Labs, Owlstone Medical, Salix Pharmaceuticals, and Universal DX.
A version of this article appeared on Medscape.com.
, with a near doubling of the national rate of IBS over 2 years, a study has found.
The uptick is probably due to not only the direct impact of SARS-CoV-2 infection on the gastrointestinal tract but also to the psychological stress associated with pandemic life, the study team said.
“COVID infection itself can definitely cause gastrointestinal symptoms like diarrhea, nausea, and abdominal pain — and for some people, those symptoms can linger and lead to chronic conditions like IBS,” Christopher V. Almario, MD, MSHPM, lead author and gastroenterologist at Cedars-Sinai Medical Center, Los Angeles, California, told GI & Hepatology News.
“But the stress of living through the pandemic — lockdowns, fear, isolation — also likely played a major role as well in the increased prevalence of digestive disorders. Both the infection itself and the psychological toll of the pandemic can disrupt the gut-brain axis and trigger chronic digestive disorders like IBS,” Almario said.
The study was published in Neurogastroenterology & Motility.
Growing Burden of Gut Disorders
Disorders of gut-brain interaction (DGBIs) are a heterogeneous group of conditions in which gastrointestinal symptoms occur without any detectable structural or biochemical abnormalities in the digestive tract. They include IBS, functional dyspepsia, and chronic idiopathic constipation, among others.
DGBIs are highly prevalent. Research has shown that nearly 40% of people in the US meet Rome IV criteria for at least one DGBI.
Almario and colleagues assessed trends in prevalence of these conditions during the COVID-19 pandemic. Starting in May 2020 through May 2022, they conducted a series of online surveys with more than 160,000 adults aged 18 or older using validated Rome IV diagnostic questionnaires.
Results showed that during the pandemic, IBS prevalence rose from 6.1% in May 2020 to 11.0% by May 2022, an increase of 0.188% per month (adjusted P < .001).
Chronic idiopathic constipation showed a smaller but statistically significant increase, from 6.0% to 6.4% (0.056% per month; adjusted P < .001).
Within the IBS subtypes, mixed-type IBS showed the largest relative increase (0.085% per month), followed by IBS with constipation (0.041% per month) and IBS with diarrhea (0.037% per month).
There were no significant changes in the prevalence of other DGBIs, such as functional bloating, functional diarrhea, or functional dyspepsia, during the study period.
Almario told GI & Hepatology News only about 9% of those surveyed reported a positive COVID test at the time of the surveys, but that figure probably underrepresents actual infections, especially in the early months of the pandemic. “Most of the survey responses came in during the earlier phases of the pandemic, and the percentage reporting a positive test increased over time,” he explained.
Almario also noted that this study did not directly compare digestive disorder rates between infected and uninfected individuals. However, a separate study by the Cedars-Sinai team currently undergoing peer review addresses that question more directly. “That study, along with several other studies, show that having COVID increases the risk of developing conditions like IBS and functional dyspepsia,” Almario said.
Taken together, the findings “underscore the increasing healthcare and economic burden of DGBI in the post-pandemic era, emphasizing the need for targeted efforts to effectively diagnose and manage these complex conditions,” they wrote.
“This will be especially challenging for healthcare systems to address, given the existing shortage of primary care physicians and gastroenterologists — clinicians who primarily manage individuals with DGBI,” they noted.
Support for this study was received from Ironwood Pharmaceuticals and Salix Pharmaceuticals in the form of institutional research grants to Cedars-Sinai. Almario has consulted for Exact Sciences, Greenspace Labs, Owlstone Medical, Salix Pharmaceuticals, and Universal DX.
A version of this article appeared on Medscape.com.
How Common Meds Can Secretly Wreck Your Patients’ Microbiome
Effective ways to combat harmful viruses, bacteria, fungi, and parasitic worms have driven major advances in medicine and contributed to a significant increase in human life expectancy over the past century. However, as knowledge about the role of these microorganisms in promoting and maintaining health deepens, there is a need for a new look at the impact of these treatments.
The list of drugs that can directly alter the gut microbiota is long. In addition to antibiotics, antivirals, antifungals, anthelmintics, proton pump inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), laxatives, oral antidiabetics, antidepressants, antipsychotics, statins, chemotherapeutics, and immunosuppressants can trigger dysbiosis.
A 2020 study published in Nature Communications, which analyzed the impact of common medications on the composition and metabolic function of the gut bacteria, showed that , most notably antibiotics, proton pump inhibitors, laxatives, and metformin.
“There are still no protocols aimed at preserving the microbiota during pharmacological treatment. Future research should identify biomarkers of drug-induced dysbiosis and potentially adapt live biotherapeutics to counteract it,” said Maria Júlia Segantini, MD, a coloproctologist at the University of São Paulo, Brazil.
Known Facts
Antibiotics, antivirals, antifungals, and anthelmintics eliminate pathogens but can also disrupt the microbiota across the gut, skin, mouth, lungs, and genitourinary tract.
“This ecosystem is part of the innate immune system and helps to balance inflammation and homeostasis. Loss of microbial diversity alters interspecies interactions and changes nutrient availability, which can undermine the ability to fend off pathogens,” said Segantini, noting the role of microbiota in vitamin K and B-complex production.
“The microbiome may lose its ability to prevent pathogens from taking hold. This is due to the loss of microbial diversity, changes in interactions between species, and the availability of nutrients,” she added.
Antibiotics, as is well known, eliminate bacterial species indiscriminately, reduce the presence of beneficial bacteria in the gut, and, therefore, favor the growth of opportunistic pathogenic microorganisms. However, in addition to their direct effects on microorganisms, different medications can alter the intestinal microbiota through various mechanisms linked to their specific actions. Here are some examples:
Proton pump inhibitors: These can facilitate the translocation of bacteria from the mouth to the intestine and affect the metabolic functions of the intestinal microbiota. “In users of these medications, there may be an enrichment of pathways related to carbohydrate metabolism, such as glycolysis and pyruvate metabolism, indicating possible changes in intestinal metabolism,” Segantini explained.
NSAIDs: NSAIDs can modify the function and composition of the intestinal microbiota, favor the growth of pathogenic species, and reduce the diversity of preexisting bacteria by reducing the presence of beneficial commensal bacteria, such as Lactobacillus and Bifidobacterium. “This is due to changes in the permeability of the intestinal wall, due to the inhibition of prostaglandins that help maintain the integrity of the intestinal barrier, enteropathy induced by NSAIDs, and drug interactions,” said Segantini.
Laxatives: Accelerated intestinal transit using laxatives impairs the quality of the microbiota and alters bile acid. Osmotic agents, such as lactulose and polyethylene glycol, may decrease resistance to infection.
“Studies in animal models indicate that polyethylene glycol can increase the proportion of Bacteroides and reduce the abundance of Bacteroidales bacteria, with lasting repercussions on the intestinal microbiota. Stimulant laxatives, in addition to causing an acceleration of the evacuation flow, can lead to a decrease in the production of short-chain fatty acids, which are important for intestinal health,” Segantini explained.
Chemotherapeutics: Chemotherapeutic agents can significantly influence the intestinal microbiota and affect its composition, diversity, and functionality, which in turn can affect the efficacy of treatment and the occurrence of adverse effects. “5-fluorouracil led to a decrease in the abundance of beneficial anaerobic genera, such as Blautia, and an increase in opportunistic pathogens, such as Staphylococcus and Escherichia coli, during chemotherapy. In addition, it can lead to an increase in the abundance of Bacteroidetes and Proteobacteria while reducing Firmicutes and Actinobacteria. These changes can affect the function of the intestinal barrier and the immune response. Other problems related to chemotherapy-induced dysbiosis are the adverse effects themselves, such as diarrhea and mucositis,” said Segantini.
Statins: Animal studies suggest that treatment with statins, including atorvastatin, may alter the composition of the gut microbiota. “These changes include the reduction of beneficial bacteria, such as Akkermansia muciniphila, and the increase in intestinal pathogens, resulting in intestinal dysbiosis. The use of statins can affect the diversity of the intestinal microbiota, although the results vary according to the type of statin and the clinical context.”
“Statins can activate intestinal nuclear receptors, such as pregnane X receptors, which modulate the expression of genes involved in bile metabolism and the inflammatory response. This activation can contribute to changes in the intestinal microbiota and associated metabolic processes. Although statins play a fundamental role in reducing cardiovascular risk, their interactions with the intestinal microbiota can influence the efficacy of treatment and the profile of adverse effects,” said Segantini.
Immunosuppressants: The use of immunosuppressants, such as corticosteroids, tacrolimus, and mycophenolate, has been associated with changes in the composition of the intestinal microbiota. “Immunosuppressant-induced dysbiosis can compromise the intestinal barrier, increase permeability, and facilitate bacterial translocation. This can result in opportunistic infections by pathogens and post-transplant complications, such as graft rejection and post-transplant diabetes,” Segantini stated.
“Alteration of the gut microbiota by immunosuppressants may influence the host’s immune response. For example, tacrolimus has been associated with an increase in the abundance of Allobaculum, Bacteroides, and Lactobacillus, in addition to elevated levels of regulatory T cells in the colonic mucosa and circulation, suggesting a role in modulating gut immunity,” she said.
Antipsychotics: Antipsychotics can affect gut microbiota in several ways, influencing bacterial composition and diversity, which may contribute to adverse metabolic and gastrointestinal effects.
“Olanzapine, for example, has been shown in rodent studies to increase the abundance of Firmicutes and reduce that of Bacteroidetes, resulting in a higher Firmicutes/Bacteroidetes ratio, which is associated with weight gain and dyslipidemia,” said Segantini.
She stated that risperidone increased the abundance of Firmicutes and decreased that of Bacteroidetes in animal models, correlating with weight gain and reduced basal metabolic rate. “Fecal transfer from risperidone-treated mice to naive mice resulted in decreased metabolic rate, suggesting that the gut microbiota would mediate these effects.”
Treatment with aripiprazole increased microbial diversity and the abundance of Clostridium, Peptoclostridium, Intestinibacter, and Christensenellaceae, in addition to promoting increased intestinal permeability in animal models.
“Therefore, the use of these medications can lead to metabolic changes, such as weight gain, hyperglycemia, dyslipidemia, and hypertension. This is due to a decrease in the production of short-chain fatty acids, which are important for maintaining the integrity of the intestinal barrier. Another change frequently observed in clinical practice is constipation induced by these medications. This functional change can also generate changes in the intestinal microbiota,” she said.
Oral antidiabetic agents: Oral antidiabetic agents influence the intestinal microbiota in different ways, depending on the therapeutic class. However, not all drug interactions in the microbiome are harmful. Liraglutide, a GLP-1 receptor agonist, promotes the growth of beneficial bacteria associated with metabolism.
“Exenatide, another GLP-1 agonist, has varied effects and can increase both beneficial and inflammatory bacteria,” explained Álvaro Delgado, MD, a gastroenterologist at Hospital Alemão Oswaldo Cruz in São Paulo, Brazil.
“In humans, an increase in bacteria such as Faecalibacterium prausnitzii has been observed, with positive effects. However, more studies are needed to evaluate the clinical impacts,” he said, and that, in animal models, these changes caused by GLP-1 agonists are linked to metabolic changes, such as greater glucose tolerance.
Metformin has been linked to increased abundance of A muciniphila, a beneficial bacterium that degrades mucin and produces short-chain fatty acids. “These bacteria are associated with improved insulin sensitivity and reduced inflammation,” he said.
Segantini stated that studies in mice have shown that vildagliptin also plays a positive role in altering the composition of the intestinal microbiota, increasing the abundance of Lactobacillus and Roseburia, and reducing Oscillibacter. “This same beneficial effect is seen with the use of sitagliptin,” she said.
Studies in animal models have also indicated that empagliflozin and dapagliflozin increase the populations of short-chain fatty acid-producing bacteria, such as Bacteroides and Odoribacter, and reduce the populations of lipopolysaccharide-producing bacteria, such as Oscillibacter.
“There are still not many studies regarding the use of sulfonylureas on the intestinal microbiota, so their action on the microbiota is still controversial,” said Segantini.
Antivirals: Antiviral treatment can influence gut microbiota in complex ways, depending on the type of infection and medication used.
“Although many studies focus on the effects of viral infection on the microbiota, there is evidence that antiviral treatment can also restore the healthy composition of the microbiota, promoting additional benefits to gut and immune health,” said Segantini.
In mice with chronic hepatitis B, entecavir restored the alpha diversity of the gut microbiota, which was reduced due to infection. In addition, the recovery of beneficial bacteria, such as Akkermansia and Blautia, was observed, which was associated with the protection of the intestinal barrier and reduction of hepatic inflammation.
Studies have indicated that tenofovir may aid in the recovery of intestinal dysbiosis induced by chronic hepatitis B virus infection and promote the restoration of a healthy microbial composition.
“Specifically, an increase in Collinsella and Bifidobacterium, bacteria associated with the production of short-chain fatty acids and modulation of the immune response, was observed,” said Segantini.
The use of antiretrovirals, such as lopinavir and ritonavir, has been associated with changes in the composition of the intestinal microbiota in patients living with HIV.
“A decrease in Lachnospira, Butyricicoccus, Oscillospira, and Prevotella, bacteria that produce short-chain fatty acids that are important in intestinal health and in modulating the immune response, was observed.”
Antifungals: As a side effect, antifungals also eliminate commensal fungi, which “share intestinal niches with microbiota bacteria, balancing their immunological functions. When modified, they culminate in dysbiosis, worsening of inflammatory pathologies — such as colitis and allergic diseases — and can increase bacterial translocation,” said Segantini.
For example, fluconazole reduces the abundance of Candida spp. while promoting the growth of fungi such as Aspergillus, Wallemia, and Epicoccum.
“A relative increase in Firmicutes and Proteobacteria and a decrease in Bacteroidetes, Deferribacteres, Patescibacteria, and Tenericutes were also observed,” she explained.
Anthelmintics: These also affect the intestinal bacterial and fungal microbiota and alter the modulation of the immune response, in addition to having specific effects depending on the type of drug used.
Clinical Advice
Symptoms of dysbiosis include abdominal distension, flatulence, constipation or diarrhea, pain, fatigue, and mood swings. “The diagnosis is made based on the clinical picture, since tests such as small intestinal bacterial overgrowth, which indicate metabolites of bacteria associated with dysbiosis, specific stool tests, and microbiota mapping with GI-MAP [Gastrointestinal Microbial Assay Plus], for example, are expensive, difficult to access, and often inconclusive for diagnosis and for assessing the cause of the microbiota alteration,” explained Fernando Seefelder Flaquer, MD, a gastroenterologist at Albert Einstein Israelite Hospital in São Paulo.
When caused by medication, dysbiosis tends to be reversed naturally after discontinuation of the drug. “However, in medications with a high chance of altering the microbiota, probiotics can be used as prevention,” said Flaquer.
“To avoid problems, it is important to use antibiotics with caution and prefer, when possible, those with a reduced spectrum,” advised Delgado.
“Supplementation with probiotics and prebiotics can help maintain the balance of the microbiota, but it should be evaluated on a case-by-case basis, as its indications are still restricted at present.”
Currently, dysbiosis management relies on nutritional support and lifestyle modifications. “Physical exercise, management of psychological changes, and use of probiotics and prebiotics. In specific cases, individualized treatment may even require the administration of some types of antibiotics,” explained Segantini.
Although fecal microbiota transplantation (FMT) has been widely discussed and increasingly studied, it should still be approached with caution. While promising, FMT remains experimental for most conditions, and its use outside research settings should be carefully considered, particularly in patients who are immunocompromised or have compromised intestinal barriers.
“Currently, the treatment has stood out as promising for cases of recurrent Clostridioides difficile infection, being the only consolidated clinical indication,” said Segantini.
Science Hype
The interest in gut microbiome research has undoubtedly driven important scientific advances, but it also risks exaggeration. While the field holds enormous promise, much of the research remains in its early stages.
“The indiscriminate use of probiotics and reliance on microbiota analysis tests for personalized probiotic prescriptions are growing concerns,” Delgado warned. “We need to bridge the gap between basic science and clinical application. When that translation happens, it could revolutionize care for many diseases.”
Flaquer emphasized a broader issue: “There has been an overvaluation of dysbiosis and microbiota-focused treatments as cure-alls for a wide range of conditions — often subjective or lacking solid scientific correlation — such as depression, anxiety, fatigue, cancer, and even autism.”
With ongoing advances in microbiome research, understanding the impact of this complex ecosystem on human health has become essential across all medical specialties. In pediatrics, for instance, microbiota plays a critical role in immune and metabolic development, particularly in preventing conditions such as allergies and obesity.
In digestive surgery, preoperative use of probiotics has been shown to reduce complications and enhance postoperative recovery. Neurological research has highlighted the gut-brain axis as a potential factor in the development of neurodegenerative diseases. In gynecology, regulating the vaginal microbiota is key to preventing infections and complications during pregnancy.
“Given the connections between the microbiota and both intestinal and systemic diseases, every medical specialist should understand how it relates to the conditions they treat daily,” concluded Flaquer.
This story was translated from Medscape’s Portuguese edition.
Effective ways to combat harmful viruses, bacteria, fungi, and parasitic worms have driven major advances in medicine and contributed to a significant increase in human life expectancy over the past century. However, as knowledge about the role of these microorganisms in promoting and maintaining health deepens, there is a need for a new look at the impact of these treatments.
The list of drugs that can directly alter the gut microbiota is long. In addition to antibiotics, antivirals, antifungals, anthelmintics, proton pump inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), laxatives, oral antidiabetics, antidepressants, antipsychotics, statins, chemotherapeutics, and immunosuppressants can trigger dysbiosis.
A 2020 study published in Nature Communications, which analyzed the impact of common medications on the composition and metabolic function of the gut bacteria, showed that , most notably antibiotics, proton pump inhibitors, laxatives, and metformin.
“There are still no protocols aimed at preserving the microbiota during pharmacological treatment. Future research should identify biomarkers of drug-induced dysbiosis and potentially adapt live biotherapeutics to counteract it,” said Maria Júlia Segantini, MD, a coloproctologist at the University of São Paulo, Brazil.
Known Facts
Antibiotics, antivirals, antifungals, and anthelmintics eliminate pathogens but can also disrupt the microbiota across the gut, skin, mouth, lungs, and genitourinary tract.
“This ecosystem is part of the innate immune system and helps to balance inflammation and homeostasis. Loss of microbial diversity alters interspecies interactions and changes nutrient availability, which can undermine the ability to fend off pathogens,” said Segantini, noting the role of microbiota in vitamin K and B-complex production.
“The microbiome may lose its ability to prevent pathogens from taking hold. This is due to the loss of microbial diversity, changes in interactions between species, and the availability of nutrients,” she added.
Antibiotics, as is well known, eliminate bacterial species indiscriminately, reduce the presence of beneficial bacteria in the gut, and, therefore, favor the growth of opportunistic pathogenic microorganisms. However, in addition to their direct effects on microorganisms, different medications can alter the intestinal microbiota through various mechanisms linked to their specific actions. Here are some examples:
Proton pump inhibitors: These can facilitate the translocation of bacteria from the mouth to the intestine and affect the metabolic functions of the intestinal microbiota. “In users of these medications, there may be an enrichment of pathways related to carbohydrate metabolism, such as glycolysis and pyruvate metabolism, indicating possible changes in intestinal metabolism,” Segantini explained.
NSAIDs: NSAIDs can modify the function and composition of the intestinal microbiota, favor the growth of pathogenic species, and reduce the diversity of preexisting bacteria by reducing the presence of beneficial commensal bacteria, such as Lactobacillus and Bifidobacterium. “This is due to changes in the permeability of the intestinal wall, due to the inhibition of prostaglandins that help maintain the integrity of the intestinal barrier, enteropathy induced by NSAIDs, and drug interactions,” said Segantini.
Laxatives: Accelerated intestinal transit using laxatives impairs the quality of the microbiota and alters bile acid. Osmotic agents, such as lactulose and polyethylene glycol, may decrease resistance to infection.
“Studies in animal models indicate that polyethylene glycol can increase the proportion of Bacteroides and reduce the abundance of Bacteroidales bacteria, with lasting repercussions on the intestinal microbiota. Stimulant laxatives, in addition to causing an acceleration of the evacuation flow, can lead to a decrease in the production of short-chain fatty acids, which are important for intestinal health,” Segantini explained.
Chemotherapeutics: Chemotherapeutic agents can significantly influence the intestinal microbiota and affect its composition, diversity, and functionality, which in turn can affect the efficacy of treatment and the occurrence of adverse effects. “5-fluorouracil led to a decrease in the abundance of beneficial anaerobic genera, such as Blautia, and an increase in opportunistic pathogens, such as Staphylococcus and Escherichia coli, during chemotherapy. In addition, it can lead to an increase in the abundance of Bacteroidetes and Proteobacteria while reducing Firmicutes and Actinobacteria. These changes can affect the function of the intestinal barrier and the immune response. Other problems related to chemotherapy-induced dysbiosis are the adverse effects themselves, such as diarrhea and mucositis,” said Segantini.
Statins: Animal studies suggest that treatment with statins, including atorvastatin, may alter the composition of the gut microbiota. “These changes include the reduction of beneficial bacteria, such as Akkermansia muciniphila, and the increase in intestinal pathogens, resulting in intestinal dysbiosis. The use of statins can affect the diversity of the intestinal microbiota, although the results vary according to the type of statin and the clinical context.”
“Statins can activate intestinal nuclear receptors, such as pregnane X receptors, which modulate the expression of genes involved in bile metabolism and the inflammatory response. This activation can contribute to changes in the intestinal microbiota and associated metabolic processes. Although statins play a fundamental role in reducing cardiovascular risk, their interactions with the intestinal microbiota can influence the efficacy of treatment and the profile of adverse effects,” said Segantini.
Immunosuppressants: The use of immunosuppressants, such as corticosteroids, tacrolimus, and mycophenolate, has been associated with changes in the composition of the intestinal microbiota. “Immunosuppressant-induced dysbiosis can compromise the intestinal barrier, increase permeability, and facilitate bacterial translocation. This can result in opportunistic infections by pathogens and post-transplant complications, such as graft rejection and post-transplant diabetes,” Segantini stated.
“Alteration of the gut microbiota by immunosuppressants may influence the host’s immune response. For example, tacrolimus has been associated with an increase in the abundance of Allobaculum, Bacteroides, and Lactobacillus, in addition to elevated levels of regulatory T cells in the colonic mucosa and circulation, suggesting a role in modulating gut immunity,” she said.
Antipsychotics: Antipsychotics can affect gut microbiota in several ways, influencing bacterial composition and diversity, which may contribute to adverse metabolic and gastrointestinal effects.
“Olanzapine, for example, has been shown in rodent studies to increase the abundance of Firmicutes and reduce that of Bacteroidetes, resulting in a higher Firmicutes/Bacteroidetes ratio, which is associated with weight gain and dyslipidemia,” said Segantini.
She stated that risperidone increased the abundance of Firmicutes and decreased that of Bacteroidetes in animal models, correlating with weight gain and reduced basal metabolic rate. “Fecal transfer from risperidone-treated mice to naive mice resulted in decreased metabolic rate, suggesting that the gut microbiota would mediate these effects.”
Treatment with aripiprazole increased microbial diversity and the abundance of Clostridium, Peptoclostridium, Intestinibacter, and Christensenellaceae, in addition to promoting increased intestinal permeability in animal models.
“Therefore, the use of these medications can lead to metabolic changes, such as weight gain, hyperglycemia, dyslipidemia, and hypertension. This is due to a decrease in the production of short-chain fatty acids, which are important for maintaining the integrity of the intestinal barrier. Another change frequently observed in clinical practice is constipation induced by these medications. This functional change can also generate changes in the intestinal microbiota,” she said.
Oral antidiabetic agents: Oral antidiabetic agents influence the intestinal microbiota in different ways, depending on the therapeutic class. However, not all drug interactions in the microbiome are harmful. Liraglutide, a GLP-1 receptor agonist, promotes the growth of beneficial bacteria associated with metabolism.
“Exenatide, another GLP-1 agonist, has varied effects and can increase both beneficial and inflammatory bacteria,” explained Álvaro Delgado, MD, a gastroenterologist at Hospital Alemão Oswaldo Cruz in São Paulo, Brazil.
“In humans, an increase in bacteria such as Faecalibacterium prausnitzii has been observed, with positive effects. However, more studies are needed to evaluate the clinical impacts,” he said, and that, in animal models, these changes caused by GLP-1 agonists are linked to metabolic changes, such as greater glucose tolerance.
Metformin has been linked to increased abundance of A muciniphila, a beneficial bacterium that degrades mucin and produces short-chain fatty acids. “These bacteria are associated with improved insulin sensitivity and reduced inflammation,” he said.
Segantini stated that studies in mice have shown that vildagliptin also plays a positive role in altering the composition of the intestinal microbiota, increasing the abundance of Lactobacillus and Roseburia, and reducing Oscillibacter. “This same beneficial effect is seen with the use of sitagliptin,” she said.
Studies in animal models have also indicated that empagliflozin and dapagliflozin increase the populations of short-chain fatty acid-producing bacteria, such as Bacteroides and Odoribacter, and reduce the populations of lipopolysaccharide-producing bacteria, such as Oscillibacter.
“There are still not many studies regarding the use of sulfonylureas on the intestinal microbiota, so their action on the microbiota is still controversial,” said Segantini.
Antivirals: Antiviral treatment can influence gut microbiota in complex ways, depending on the type of infection and medication used.
“Although many studies focus on the effects of viral infection on the microbiota, there is evidence that antiviral treatment can also restore the healthy composition of the microbiota, promoting additional benefits to gut and immune health,” said Segantini.
In mice with chronic hepatitis B, entecavir restored the alpha diversity of the gut microbiota, which was reduced due to infection. In addition, the recovery of beneficial bacteria, such as Akkermansia and Blautia, was observed, which was associated with the protection of the intestinal barrier and reduction of hepatic inflammation.
Studies have indicated that tenofovir may aid in the recovery of intestinal dysbiosis induced by chronic hepatitis B virus infection and promote the restoration of a healthy microbial composition.
“Specifically, an increase in Collinsella and Bifidobacterium, bacteria associated with the production of short-chain fatty acids and modulation of the immune response, was observed,” said Segantini.
The use of antiretrovirals, such as lopinavir and ritonavir, has been associated with changes in the composition of the intestinal microbiota in patients living with HIV.
“A decrease in Lachnospira, Butyricicoccus, Oscillospira, and Prevotella, bacteria that produce short-chain fatty acids that are important in intestinal health and in modulating the immune response, was observed.”
Antifungals: As a side effect, antifungals also eliminate commensal fungi, which “share intestinal niches with microbiota bacteria, balancing their immunological functions. When modified, they culminate in dysbiosis, worsening of inflammatory pathologies — such as colitis and allergic diseases — and can increase bacterial translocation,” said Segantini.
For example, fluconazole reduces the abundance of Candida spp. while promoting the growth of fungi such as Aspergillus, Wallemia, and Epicoccum.
“A relative increase in Firmicutes and Proteobacteria and a decrease in Bacteroidetes, Deferribacteres, Patescibacteria, and Tenericutes were also observed,” she explained.
Anthelmintics: These also affect the intestinal bacterial and fungal microbiota and alter the modulation of the immune response, in addition to having specific effects depending on the type of drug used.
Clinical Advice
Symptoms of dysbiosis include abdominal distension, flatulence, constipation or diarrhea, pain, fatigue, and mood swings. “The diagnosis is made based on the clinical picture, since tests such as small intestinal bacterial overgrowth, which indicate metabolites of bacteria associated with dysbiosis, specific stool tests, and microbiota mapping with GI-MAP [Gastrointestinal Microbial Assay Plus], for example, are expensive, difficult to access, and often inconclusive for diagnosis and for assessing the cause of the microbiota alteration,” explained Fernando Seefelder Flaquer, MD, a gastroenterologist at Albert Einstein Israelite Hospital in São Paulo.
When caused by medication, dysbiosis tends to be reversed naturally after discontinuation of the drug. “However, in medications with a high chance of altering the microbiota, probiotics can be used as prevention,” said Flaquer.
“To avoid problems, it is important to use antibiotics with caution and prefer, when possible, those with a reduced spectrum,” advised Delgado.
“Supplementation with probiotics and prebiotics can help maintain the balance of the microbiota, but it should be evaluated on a case-by-case basis, as its indications are still restricted at present.”
Currently, dysbiosis management relies on nutritional support and lifestyle modifications. “Physical exercise, management of psychological changes, and use of probiotics and prebiotics. In specific cases, individualized treatment may even require the administration of some types of antibiotics,” explained Segantini.
Although fecal microbiota transplantation (FMT) has been widely discussed and increasingly studied, it should still be approached with caution. While promising, FMT remains experimental for most conditions, and its use outside research settings should be carefully considered, particularly in patients who are immunocompromised or have compromised intestinal barriers.
“Currently, the treatment has stood out as promising for cases of recurrent Clostridioides difficile infection, being the only consolidated clinical indication,” said Segantini.
Science Hype
The interest in gut microbiome research has undoubtedly driven important scientific advances, but it also risks exaggeration. While the field holds enormous promise, much of the research remains in its early stages.
“The indiscriminate use of probiotics and reliance on microbiota analysis tests for personalized probiotic prescriptions are growing concerns,” Delgado warned. “We need to bridge the gap between basic science and clinical application. When that translation happens, it could revolutionize care for many diseases.”
Flaquer emphasized a broader issue: “There has been an overvaluation of dysbiosis and microbiota-focused treatments as cure-alls for a wide range of conditions — often subjective or lacking solid scientific correlation — such as depression, anxiety, fatigue, cancer, and even autism.”
With ongoing advances in microbiome research, understanding the impact of this complex ecosystem on human health has become essential across all medical specialties. In pediatrics, for instance, microbiota plays a critical role in immune and metabolic development, particularly in preventing conditions such as allergies and obesity.
In digestive surgery, preoperative use of probiotics has been shown to reduce complications and enhance postoperative recovery. Neurological research has highlighted the gut-brain axis as a potential factor in the development of neurodegenerative diseases. In gynecology, regulating the vaginal microbiota is key to preventing infections and complications during pregnancy.
“Given the connections between the microbiota and both intestinal and systemic diseases, every medical specialist should understand how it relates to the conditions they treat daily,” concluded Flaquer.
This story was translated from Medscape’s Portuguese edition.
Effective ways to combat harmful viruses, bacteria, fungi, and parasitic worms have driven major advances in medicine and contributed to a significant increase in human life expectancy over the past century. However, as knowledge about the role of these microorganisms in promoting and maintaining health deepens, there is a need for a new look at the impact of these treatments.
The list of drugs that can directly alter the gut microbiota is long. In addition to antibiotics, antivirals, antifungals, anthelmintics, proton pump inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), laxatives, oral antidiabetics, antidepressants, antipsychotics, statins, chemotherapeutics, and immunosuppressants can trigger dysbiosis.
A 2020 study published in Nature Communications, which analyzed the impact of common medications on the composition and metabolic function of the gut bacteria, showed that , most notably antibiotics, proton pump inhibitors, laxatives, and metformin.
“There are still no protocols aimed at preserving the microbiota during pharmacological treatment. Future research should identify biomarkers of drug-induced dysbiosis and potentially adapt live biotherapeutics to counteract it,” said Maria Júlia Segantini, MD, a coloproctologist at the University of São Paulo, Brazil.
Known Facts
Antibiotics, antivirals, antifungals, and anthelmintics eliminate pathogens but can also disrupt the microbiota across the gut, skin, mouth, lungs, and genitourinary tract.
“This ecosystem is part of the innate immune system and helps to balance inflammation and homeostasis. Loss of microbial diversity alters interspecies interactions and changes nutrient availability, which can undermine the ability to fend off pathogens,” said Segantini, noting the role of microbiota in vitamin K and B-complex production.
“The microbiome may lose its ability to prevent pathogens from taking hold. This is due to the loss of microbial diversity, changes in interactions between species, and the availability of nutrients,” she added.
Antibiotics, as is well known, eliminate bacterial species indiscriminately, reduce the presence of beneficial bacteria in the gut, and, therefore, favor the growth of opportunistic pathogenic microorganisms. However, in addition to their direct effects on microorganisms, different medications can alter the intestinal microbiota through various mechanisms linked to their specific actions. Here are some examples:
Proton pump inhibitors: These can facilitate the translocation of bacteria from the mouth to the intestine and affect the metabolic functions of the intestinal microbiota. “In users of these medications, there may be an enrichment of pathways related to carbohydrate metabolism, such as glycolysis and pyruvate metabolism, indicating possible changes in intestinal metabolism,” Segantini explained.
NSAIDs: NSAIDs can modify the function and composition of the intestinal microbiota, favor the growth of pathogenic species, and reduce the diversity of preexisting bacteria by reducing the presence of beneficial commensal bacteria, such as Lactobacillus and Bifidobacterium. “This is due to changes in the permeability of the intestinal wall, due to the inhibition of prostaglandins that help maintain the integrity of the intestinal barrier, enteropathy induced by NSAIDs, and drug interactions,” said Segantini.
Laxatives: Accelerated intestinal transit using laxatives impairs the quality of the microbiota and alters bile acid. Osmotic agents, such as lactulose and polyethylene glycol, may decrease resistance to infection.
“Studies in animal models indicate that polyethylene glycol can increase the proportion of Bacteroides and reduce the abundance of Bacteroidales bacteria, with lasting repercussions on the intestinal microbiota. Stimulant laxatives, in addition to causing an acceleration of the evacuation flow, can lead to a decrease in the production of short-chain fatty acids, which are important for intestinal health,” Segantini explained.
Chemotherapeutics: Chemotherapeutic agents can significantly influence the intestinal microbiota and affect its composition, diversity, and functionality, which in turn can affect the efficacy of treatment and the occurrence of adverse effects. “5-fluorouracil led to a decrease in the abundance of beneficial anaerobic genera, such as Blautia, and an increase in opportunistic pathogens, such as Staphylococcus and Escherichia coli, during chemotherapy. In addition, it can lead to an increase in the abundance of Bacteroidetes and Proteobacteria while reducing Firmicutes and Actinobacteria. These changes can affect the function of the intestinal barrier and the immune response. Other problems related to chemotherapy-induced dysbiosis are the adverse effects themselves, such as diarrhea and mucositis,” said Segantini.
Statins: Animal studies suggest that treatment with statins, including atorvastatin, may alter the composition of the gut microbiota. “These changes include the reduction of beneficial bacteria, such as Akkermansia muciniphila, and the increase in intestinal pathogens, resulting in intestinal dysbiosis. The use of statins can affect the diversity of the intestinal microbiota, although the results vary according to the type of statin and the clinical context.”
“Statins can activate intestinal nuclear receptors, such as pregnane X receptors, which modulate the expression of genes involved in bile metabolism and the inflammatory response. This activation can contribute to changes in the intestinal microbiota and associated metabolic processes. Although statins play a fundamental role in reducing cardiovascular risk, their interactions with the intestinal microbiota can influence the efficacy of treatment and the profile of adverse effects,” said Segantini.
Immunosuppressants: The use of immunosuppressants, such as corticosteroids, tacrolimus, and mycophenolate, has been associated with changes in the composition of the intestinal microbiota. “Immunosuppressant-induced dysbiosis can compromise the intestinal barrier, increase permeability, and facilitate bacterial translocation. This can result in opportunistic infections by pathogens and post-transplant complications, such as graft rejection and post-transplant diabetes,” Segantini stated.
“Alteration of the gut microbiota by immunosuppressants may influence the host’s immune response. For example, tacrolimus has been associated with an increase in the abundance of Allobaculum, Bacteroides, and Lactobacillus, in addition to elevated levels of regulatory T cells in the colonic mucosa and circulation, suggesting a role in modulating gut immunity,” she said.
Antipsychotics: Antipsychotics can affect gut microbiota in several ways, influencing bacterial composition and diversity, which may contribute to adverse metabolic and gastrointestinal effects.
“Olanzapine, for example, has been shown in rodent studies to increase the abundance of Firmicutes and reduce that of Bacteroidetes, resulting in a higher Firmicutes/Bacteroidetes ratio, which is associated with weight gain and dyslipidemia,” said Segantini.
She stated that risperidone increased the abundance of Firmicutes and decreased that of Bacteroidetes in animal models, correlating with weight gain and reduced basal metabolic rate. “Fecal transfer from risperidone-treated mice to naive mice resulted in decreased metabolic rate, suggesting that the gut microbiota would mediate these effects.”
Treatment with aripiprazole increased microbial diversity and the abundance of Clostridium, Peptoclostridium, Intestinibacter, and Christensenellaceae, in addition to promoting increased intestinal permeability in animal models.
“Therefore, the use of these medications can lead to metabolic changes, such as weight gain, hyperglycemia, dyslipidemia, and hypertension. This is due to a decrease in the production of short-chain fatty acids, which are important for maintaining the integrity of the intestinal barrier. Another change frequently observed in clinical practice is constipation induced by these medications. This functional change can also generate changes in the intestinal microbiota,” she said.
Oral antidiabetic agents: Oral antidiabetic agents influence the intestinal microbiota in different ways, depending on the therapeutic class. However, not all drug interactions in the microbiome are harmful. Liraglutide, a GLP-1 receptor agonist, promotes the growth of beneficial bacteria associated with metabolism.
“Exenatide, another GLP-1 agonist, has varied effects and can increase both beneficial and inflammatory bacteria,” explained Álvaro Delgado, MD, a gastroenterologist at Hospital Alemão Oswaldo Cruz in São Paulo, Brazil.
“In humans, an increase in bacteria such as Faecalibacterium prausnitzii has been observed, with positive effects. However, more studies are needed to evaluate the clinical impacts,” he said, and that, in animal models, these changes caused by GLP-1 agonists are linked to metabolic changes, such as greater glucose tolerance.
Metformin has been linked to increased abundance of A muciniphila, a beneficial bacterium that degrades mucin and produces short-chain fatty acids. “These bacteria are associated with improved insulin sensitivity and reduced inflammation,” he said.
Segantini stated that studies in mice have shown that vildagliptin also plays a positive role in altering the composition of the intestinal microbiota, increasing the abundance of Lactobacillus and Roseburia, and reducing Oscillibacter. “This same beneficial effect is seen with the use of sitagliptin,” she said.
Studies in animal models have also indicated that empagliflozin and dapagliflozin increase the populations of short-chain fatty acid-producing bacteria, such as Bacteroides and Odoribacter, and reduce the populations of lipopolysaccharide-producing bacteria, such as Oscillibacter.
“There are still not many studies regarding the use of sulfonylureas on the intestinal microbiota, so their action on the microbiota is still controversial,” said Segantini.
Antivirals: Antiviral treatment can influence gut microbiota in complex ways, depending on the type of infection and medication used.
“Although many studies focus on the effects of viral infection on the microbiota, there is evidence that antiviral treatment can also restore the healthy composition of the microbiota, promoting additional benefits to gut and immune health,” said Segantini.
In mice with chronic hepatitis B, entecavir restored the alpha diversity of the gut microbiota, which was reduced due to infection. In addition, the recovery of beneficial bacteria, such as Akkermansia and Blautia, was observed, which was associated with the protection of the intestinal barrier and reduction of hepatic inflammation.
Studies have indicated that tenofovir may aid in the recovery of intestinal dysbiosis induced by chronic hepatitis B virus infection and promote the restoration of a healthy microbial composition.
“Specifically, an increase in Collinsella and Bifidobacterium, bacteria associated with the production of short-chain fatty acids and modulation of the immune response, was observed,” said Segantini.
The use of antiretrovirals, such as lopinavir and ritonavir, has been associated with changes in the composition of the intestinal microbiota in patients living with HIV.
“A decrease in Lachnospira, Butyricicoccus, Oscillospira, and Prevotella, bacteria that produce short-chain fatty acids that are important in intestinal health and in modulating the immune response, was observed.”
Antifungals: As a side effect, antifungals also eliminate commensal fungi, which “share intestinal niches with microbiota bacteria, balancing their immunological functions. When modified, they culminate in dysbiosis, worsening of inflammatory pathologies — such as colitis and allergic diseases — and can increase bacterial translocation,” said Segantini.
For example, fluconazole reduces the abundance of Candida spp. while promoting the growth of fungi such as Aspergillus, Wallemia, and Epicoccum.
“A relative increase in Firmicutes and Proteobacteria and a decrease in Bacteroidetes, Deferribacteres, Patescibacteria, and Tenericutes were also observed,” she explained.
Anthelmintics: These also affect the intestinal bacterial and fungal microbiota and alter the modulation of the immune response, in addition to having specific effects depending on the type of drug used.
Clinical Advice
Symptoms of dysbiosis include abdominal distension, flatulence, constipation or diarrhea, pain, fatigue, and mood swings. “The diagnosis is made based on the clinical picture, since tests such as small intestinal bacterial overgrowth, which indicate metabolites of bacteria associated with dysbiosis, specific stool tests, and microbiota mapping with GI-MAP [Gastrointestinal Microbial Assay Plus], for example, are expensive, difficult to access, and often inconclusive for diagnosis and for assessing the cause of the microbiota alteration,” explained Fernando Seefelder Flaquer, MD, a gastroenterologist at Albert Einstein Israelite Hospital in São Paulo.
When caused by medication, dysbiosis tends to be reversed naturally after discontinuation of the drug. “However, in medications with a high chance of altering the microbiota, probiotics can be used as prevention,” said Flaquer.
“To avoid problems, it is important to use antibiotics with caution and prefer, when possible, those with a reduced spectrum,” advised Delgado.
“Supplementation with probiotics and prebiotics can help maintain the balance of the microbiota, but it should be evaluated on a case-by-case basis, as its indications are still restricted at present.”
Currently, dysbiosis management relies on nutritional support and lifestyle modifications. “Physical exercise, management of psychological changes, and use of probiotics and prebiotics. In specific cases, individualized treatment may even require the administration of some types of antibiotics,” explained Segantini.
Although fecal microbiota transplantation (FMT) has been widely discussed and increasingly studied, it should still be approached with caution. While promising, FMT remains experimental for most conditions, and its use outside research settings should be carefully considered, particularly in patients who are immunocompromised or have compromised intestinal barriers.
“Currently, the treatment has stood out as promising for cases of recurrent Clostridioides difficile infection, being the only consolidated clinical indication,” said Segantini.
Science Hype
The interest in gut microbiome research has undoubtedly driven important scientific advances, but it also risks exaggeration. While the field holds enormous promise, much of the research remains in its early stages.
“The indiscriminate use of probiotics and reliance on microbiota analysis tests for personalized probiotic prescriptions are growing concerns,” Delgado warned. “We need to bridge the gap between basic science and clinical application. When that translation happens, it could revolutionize care for many diseases.”
Flaquer emphasized a broader issue: “There has been an overvaluation of dysbiosis and microbiota-focused treatments as cure-alls for a wide range of conditions — often subjective or lacking solid scientific correlation — such as depression, anxiety, fatigue, cancer, and even autism.”
With ongoing advances in microbiome research, understanding the impact of this complex ecosystem on human health has become essential across all medical specialties. In pediatrics, for instance, microbiota plays a critical role in immune and metabolic development, particularly in preventing conditions such as allergies and obesity.
In digestive surgery, preoperative use of probiotics has been shown to reduce complications and enhance postoperative recovery. Neurological research has highlighted the gut-brain axis as a potential factor in the development of neurodegenerative diseases. In gynecology, regulating the vaginal microbiota is key to preventing infections and complications during pregnancy.
“Given the connections between the microbiota and both intestinal and systemic diseases, every medical specialist should understand how it relates to the conditions they treat daily,” concluded Flaquer.
This story was translated from Medscape’s Portuguese edition.
Sclerosing Mesenteritis: What GIs Need to Know About This Rare Disease
AGA has issued an updated pragmatic review on sclerosing mesenteritis (SM). Published in Clinical Gastroenterology and Hepatology, the update evaluates available evidence for diagnosis and treatment and examines opportunities for future research in SM, previously known by such names as misty mesentery, mesenteric panniculitis, and inflammatory pseudotumor.
Led by Mark T. Worthington, MD, AGAF, a professor of medicine in the Division of Gastroenterology and Hepatology at the University of Virginia in Charlottesville, Virginia, an expert AGA panel described SM as an uncommon benign idiopathic autoimmune disease of the mesenteric fat. Although of poorly understood etiology, gastroenterologists need to be prepared to diagnose it.
“CT radiologists increasingly are reporting SM and related lesions, such as misty mesentery,” Worthington told GI & Hepatology News. “We are also seeing new SM cases caused by immune checkpoint inhibitors in cancer treatment, and the oncologists ask us to manage this because it interferes with the treatment of the underlying malignancy. Those are often readily treated because we catch them so early.” Metabolic syndrome and associated conditions increase the risk for SM, as does aging.
The recent changes are intended to help clinicians predict disease activity and the need for other testing or treatment. “For instance, most cases are indolent and do not require aggressive treatment — often no treatment at all — but for those that are aggressive, we want the clinician to be able to identify those and make sure the treatment is appropriate. The aggressive cases may warrant tertiary referral,” Worthington said. “A secondary cancer is a possibility in this condition, so drawing from the SM radiology studies, we try to help the clinician decide who needs other testing, such as PET-CT or biopsy, and who can be monitored.”
As many as 60% of cases are asymptomatic, requiring no treatment. Abdominal pain is the most frequent symptom and its location on clinical examination should correspond to the SM lesion on imaging. Treatment involves anti-inflammatory medications tailored to disease severity and clinical response.
No biopsy is not necessary if the lesion meets three of the five CT criteria reported by B. Coulier and has no features of more aggressive disease or malignancy. Although some have suggested that SM may be a paraneoplastic syndrome, current evidence does not support this. SM needs to be differentiated from other diagnoses such as non-Hodgkin’s lymphoma, peritoneal carcinomatosis, and mesenteric fibromatosis.
“There are now CT guidelines for who actually has SM, who needs a biopsy or a PET-CT to rule-out malignancy, and who doesn’t,” said Worthington. “Radiologists do not always use the Coulier criteria for diagnosis, but often they will with encouragement. From this review, a GI clinician should be able to identify SM on CT.”
Epidemiologically, retrospective CT studies have reported a frequency of 0.6%-1.1%, the panelists noted. And while demographic data are limited, a large early case series reported that SM patients had a mean age of 55 years and more likely to be men and of White race.
Patients with SM do not have a higher prevalence of autoimmunity in general, but may have increased rates of metabolic syndrome, obesity, coronary artery disease, and urolithiasis, the panelists noted.
The update allows room for differences in clinical judgment. “For instance, a longer or more frequent CT surveillance interval can be justified depending on the patient’s findings, and no one should feel locked in by these recommendations,” Worthington said.
Medical Therapy
Although there is no surgical cure, pharmacologic options are many. These include prednisone, tamoxifen, colchicine, azathioprine, thalidomide, cyclophosphamide, and methotrexate, as well as the biologics rituximab, infliximab and ustekinumab. Current corticosteroid-based therapies often require months to achieve a clinical response, however.
Bowel obstruction is managed nonoperatively when feasible, but medically refractory disease may require surgical bypass.
Offering his perspective on the guidance but not involved in its formulation, Gastroenterologist Stephen B. Hanauer, MD, AGAF, a professor of medicine at Northwestern Medicine in Chicago, said, “The most useful component of the practical review is the algorithm for diagnosis and determination when biopsy or follow-up imaging is reasonable in the absence of evidence.” He stressed that the recommendations are pragmatic rather than evidence-based “as there are no controlled trials and the presentation is heterogeneous.”
Hanauer added that none of the recommended treatments have been shown to impact reduction on imaging. “Hence, all of the treatments are empiric without biological or imaging endpoints.”
In his experience, patients with inflammatory features are the best candidates for immune-directed therapies as reduction in inflammatory markers is a potential endpoint, although no therapies have demonstrated an effect on imaging or progression. “As an IBD doctor, I favor steroids and azathioprine or anti-TNF directed therapy, but again, there is no evidence beyond reports of symptomatic improvement.”
Worthington and colleagues agreed that treatment protocols have developed empirically. “Future investigation for symptomatic SM should focus on the nature of the inflammatory response, including causative cytokines and other proinflammatory mediators, the goal being targeted therapy with fewer side effects and a more rapid clinical response,” they wrote.
Currently, said Worthington, the biggest gaps remain in treatment. “Even the best studies are small and anecdotal, and we do not know the cytokine or other proinflammatory mediators.”
A version of this article appeared on Medscape.com.
AGA has issued an updated pragmatic review on sclerosing mesenteritis (SM). Published in Clinical Gastroenterology and Hepatology, the update evaluates available evidence for diagnosis and treatment and examines opportunities for future research in SM, previously known by such names as misty mesentery, mesenteric panniculitis, and inflammatory pseudotumor.
Led by Mark T. Worthington, MD, AGAF, a professor of medicine in the Division of Gastroenterology and Hepatology at the University of Virginia in Charlottesville, Virginia, an expert AGA panel described SM as an uncommon benign idiopathic autoimmune disease of the mesenteric fat. Although of poorly understood etiology, gastroenterologists need to be prepared to diagnose it.
“CT radiologists increasingly are reporting SM and related lesions, such as misty mesentery,” Worthington told GI & Hepatology News. “We are also seeing new SM cases caused by immune checkpoint inhibitors in cancer treatment, and the oncologists ask us to manage this because it interferes with the treatment of the underlying malignancy. Those are often readily treated because we catch them so early.” Metabolic syndrome and associated conditions increase the risk for SM, as does aging.
The recent changes are intended to help clinicians predict disease activity and the need for other testing or treatment. “For instance, most cases are indolent and do not require aggressive treatment — often no treatment at all — but for those that are aggressive, we want the clinician to be able to identify those and make sure the treatment is appropriate. The aggressive cases may warrant tertiary referral,” Worthington said. “A secondary cancer is a possibility in this condition, so drawing from the SM radiology studies, we try to help the clinician decide who needs other testing, such as PET-CT or biopsy, and who can be monitored.”
As many as 60% of cases are asymptomatic, requiring no treatment. Abdominal pain is the most frequent symptom and its location on clinical examination should correspond to the SM lesion on imaging. Treatment involves anti-inflammatory medications tailored to disease severity and clinical response.
No biopsy is not necessary if the lesion meets three of the five CT criteria reported by B. Coulier and has no features of more aggressive disease or malignancy. Although some have suggested that SM may be a paraneoplastic syndrome, current evidence does not support this. SM needs to be differentiated from other diagnoses such as non-Hodgkin’s lymphoma, peritoneal carcinomatosis, and mesenteric fibromatosis.
“There are now CT guidelines for who actually has SM, who needs a biopsy or a PET-CT to rule-out malignancy, and who doesn’t,” said Worthington. “Radiologists do not always use the Coulier criteria for diagnosis, but often they will with encouragement. From this review, a GI clinician should be able to identify SM on CT.”
Epidemiologically, retrospective CT studies have reported a frequency of 0.6%-1.1%, the panelists noted. And while demographic data are limited, a large early case series reported that SM patients had a mean age of 55 years and more likely to be men and of White race.
Patients with SM do not have a higher prevalence of autoimmunity in general, but may have increased rates of metabolic syndrome, obesity, coronary artery disease, and urolithiasis, the panelists noted.
The update allows room for differences in clinical judgment. “For instance, a longer or more frequent CT surveillance interval can be justified depending on the patient’s findings, and no one should feel locked in by these recommendations,” Worthington said.
Medical Therapy
Although there is no surgical cure, pharmacologic options are many. These include prednisone, tamoxifen, colchicine, azathioprine, thalidomide, cyclophosphamide, and methotrexate, as well as the biologics rituximab, infliximab and ustekinumab. Current corticosteroid-based therapies often require months to achieve a clinical response, however.
Bowel obstruction is managed nonoperatively when feasible, but medically refractory disease may require surgical bypass.
Offering his perspective on the guidance but not involved in its formulation, Gastroenterologist Stephen B. Hanauer, MD, AGAF, a professor of medicine at Northwestern Medicine in Chicago, said, “The most useful component of the practical review is the algorithm for diagnosis and determination when biopsy or follow-up imaging is reasonable in the absence of evidence.” He stressed that the recommendations are pragmatic rather than evidence-based “as there are no controlled trials and the presentation is heterogeneous.”
Hanauer added that none of the recommended treatments have been shown to impact reduction on imaging. “Hence, all of the treatments are empiric without biological or imaging endpoints.”
In his experience, patients with inflammatory features are the best candidates for immune-directed therapies as reduction in inflammatory markers is a potential endpoint, although no therapies have demonstrated an effect on imaging or progression. “As an IBD doctor, I favor steroids and azathioprine or anti-TNF directed therapy, but again, there is no evidence beyond reports of symptomatic improvement.”
Worthington and colleagues agreed that treatment protocols have developed empirically. “Future investigation for symptomatic SM should focus on the nature of the inflammatory response, including causative cytokines and other proinflammatory mediators, the goal being targeted therapy with fewer side effects and a more rapid clinical response,” they wrote.
Currently, said Worthington, the biggest gaps remain in treatment. “Even the best studies are small and anecdotal, and we do not know the cytokine or other proinflammatory mediators.”
A version of this article appeared on Medscape.com.
AGA has issued an updated pragmatic review on sclerosing mesenteritis (SM). Published in Clinical Gastroenterology and Hepatology, the update evaluates available evidence for diagnosis and treatment and examines opportunities for future research in SM, previously known by such names as misty mesentery, mesenteric panniculitis, and inflammatory pseudotumor.
Led by Mark T. Worthington, MD, AGAF, a professor of medicine in the Division of Gastroenterology and Hepatology at the University of Virginia in Charlottesville, Virginia, an expert AGA panel described SM as an uncommon benign idiopathic autoimmune disease of the mesenteric fat. Although of poorly understood etiology, gastroenterologists need to be prepared to diagnose it.
“CT radiologists increasingly are reporting SM and related lesions, such as misty mesentery,” Worthington told GI & Hepatology News. “We are also seeing new SM cases caused by immune checkpoint inhibitors in cancer treatment, and the oncologists ask us to manage this because it interferes with the treatment of the underlying malignancy. Those are often readily treated because we catch them so early.” Metabolic syndrome and associated conditions increase the risk for SM, as does aging.
The recent changes are intended to help clinicians predict disease activity and the need for other testing or treatment. “For instance, most cases are indolent and do not require aggressive treatment — often no treatment at all — but for those that are aggressive, we want the clinician to be able to identify those and make sure the treatment is appropriate. The aggressive cases may warrant tertiary referral,” Worthington said. “A secondary cancer is a possibility in this condition, so drawing from the SM radiology studies, we try to help the clinician decide who needs other testing, such as PET-CT or biopsy, and who can be monitored.”
As many as 60% of cases are asymptomatic, requiring no treatment. Abdominal pain is the most frequent symptom and its location on clinical examination should correspond to the SM lesion on imaging. Treatment involves anti-inflammatory medications tailored to disease severity and clinical response.
No biopsy is not necessary if the lesion meets three of the five CT criteria reported by B. Coulier and has no features of more aggressive disease or malignancy. Although some have suggested that SM may be a paraneoplastic syndrome, current evidence does not support this. SM needs to be differentiated from other diagnoses such as non-Hodgkin’s lymphoma, peritoneal carcinomatosis, and mesenteric fibromatosis.
“There are now CT guidelines for who actually has SM, who needs a biopsy or a PET-CT to rule-out malignancy, and who doesn’t,” said Worthington. “Radiologists do not always use the Coulier criteria for diagnosis, but often they will with encouragement. From this review, a GI clinician should be able to identify SM on CT.”
Epidemiologically, retrospective CT studies have reported a frequency of 0.6%-1.1%, the panelists noted. And while demographic data are limited, a large early case series reported that SM patients had a mean age of 55 years and more likely to be men and of White race.
Patients with SM do not have a higher prevalence of autoimmunity in general, but may have increased rates of metabolic syndrome, obesity, coronary artery disease, and urolithiasis, the panelists noted.
The update allows room for differences in clinical judgment. “For instance, a longer or more frequent CT surveillance interval can be justified depending on the patient’s findings, and no one should feel locked in by these recommendations,” Worthington said.
Medical Therapy
Although there is no surgical cure, pharmacologic options are many. These include prednisone, tamoxifen, colchicine, azathioprine, thalidomide, cyclophosphamide, and methotrexate, as well as the biologics rituximab, infliximab and ustekinumab. Current corticosteroid-based therapies often require months to achieve a clinical response, however.
Bowel obstruction is managed nonoperatively when feasible, but medically refractory disease may require surgical bypass.
Offering his perspective on the guidance but not involved in its formulation, Gastroenterologist Stephen B. Hanauer, MD, AGAF, a professor of medicine at Northwestern Medicine in Chicago, said, “The most useful component of the practical review is the algorithm for diagnosis and determination when biopsy or follow-up imaging is reasonable in the absence of evidence.” He stressed that the recommendations are pragmatic rather than evidence-based “as there are no controlled trials and the presentation is heterogeneous.”
Hanauer added that none of the recommended treatments have been shown to impact reduction on imaging. “Hence, all of the treatments are empiric without biological or imaging endpoints.”
In his experience, patients with inflammatory features are the best candidates for immune-directed therapies as reduction in inflammatory markers is a potential endpoint, although no therapies have demonstrated an effect on imaging or progression. “As an IBD doctor, I favor steroids and azathioprine or anti-TNF directed therapy, but again, there is no evidence beyond reports of symptomatic improvement.”
Worthington and colleagues agreed that treatment protocols have developed empirically. “Future investigation for symptomatic SM should focus on the nature of the inflammatory response, including causative cytokines and other proinflammatory mediators, the goal being targeted therapy with fewer side effects and a more rapid clinical response,” they wrote.
Currently, said Worthington, the biggest gaps remain in treatment. “Even the best studies are small and anecdotal, and we do not know the cytokine or other proinflammatory mediators.”
A version of this article appeared on Medscape.com.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Antibiotics Pre-Appendectomy Don’t Lower Perforation Risk, But Reduce Infections
, according to a new study.
While the percentage of surgical site infections (SSIs) was small for both groups, patients who received antibiotics during the waiting period had lower rates of these infections.
The trial — titled PERFECT-Antibiotics — was a substudy embedded in a larger PERFECT clinical trial, which aimed to determine whether an in-hospital delay of appendectomy resulted in increased risk for appendiceal perforation when compared to emergent surgery.
The trial “concluded that appendectomy does not need to be performed promptly in acute uncomplicated appendicitis and can be scheduled within 24 hours without increasing complications,” senior author Panu Mentula, MD, of the Department of Gastroenterological Surgery, Helsinki University Hospital, Helsinki, Finland, and colleagues wrote in the study. “The next question is whether preoperatively started antibiotic treatment reduces the risk of appendiceal perforations.”
The findings were published online in JAMA Surgery on May 14, 2025.
Trial Design
PERFECT-Antibiotics was an open-label, randomized trial conducted at two hospitals in Finland and one hospital in Norway. Researchers enrolled 1774 individuals diagnosed with acute uncomplicated appendicitis, diagnosed clinically or via imaging. Patients were placed in one of two groups: The antibiotic group received intravenous (IV) cefuroxime (1500 mg) and metronidazole (500 mg) every 8 hours until surgery, while the nonantibiotic group waited for surgery without antibiotics.
All patients received one dose of IV cefuroxime (1500 mg) and metronidazole (500 mg) during anesthesia induction. The primary outcome was perforated appendicitis and secondary outcomes included complication rate and SSIs within 30 days of follow-up.
The median age of patients was 35 years (interquartile range [IQR], 28-46 years), and 55% of patients were men. Patients waited a median time of 9 hours (IQR, 4.3-15.5) from study randomization to undergoing surgery.
No Difference in Appendiceal Perforation
Of the 888 patients in the preoperative antibiotic group, 26.2% received one dose, 38.7% received two doses, 22.6% received three doses, and 11.8% received four or more doses of antibiotics, including the antibiotic dose given during anesthesia. A total of 74 patients (8.3%) in this group had a perforated appendix.
Of the 886 patients not given preoperative antibiotics, 79 (8.9%) had a perforated appendix, which met the predetermined noninferiority threshold.
The groups had similar complication rates over the 30-day follow-up, though SSIs were lower in the antibiotic group (1.6%) than the no antibiotic group (3.2%).
The researchers estimated that the number needed to treat for antibiotic therapy was 63 for SSIs, 83 for intra-abdominal SSI, and 125 for reintervention.
“Although longer preoperative antibiotic treatment resulted in slightly lower rate of postoperative infectious complications, the actual difference was very small and probably clinically not significant to justify longer preoperative antibiotic treatment,” Mentula and colleagues wrote.
Lower Infection Rates With Antibiotics
Commenting on the study for GI & Hepatology News, Theodore Pappas, MD, professor of surgery at Duke University School of Medicine in Durham, North Carolina, placed greater importance on these secondary outcomes.
Intra-abdominal infections, a subset of SSIs, were more than twice as common in the no-antibiotic group (1.9%) than in the antibiotic group (0.7%; P = .02). Positive blood cultures were also more common in the no-antibiotic group than the antibiotic group (P = .02).
While the authors qualified these results, “the reality was it was better to use antibiotics,” he said.
There was also a “big overlap between the two groups,” he said, which may have muted differences between the two groups. For example, one fourth of patients in the antibiotic group received only one dose of antibiotics, the same treatment regimen as the no-antibiotic group.
“Although protocol required prophylaxis in all patients in the induction of anesthesia, some clinicians thought that it was unnecessary, because antibiotics had already been given only a couple of hours ago” in patients in the antibiotic group, Mentula told GI & Hepatology News. She did not think that would affect the study’s results.
The PERFECT trial and the antibiotics subtrial answer two important questions that have been asked for years, Pappas continued: Whether appendectomy for uncomplicated acute appendicitis needs to be performed emergently and if antibiotics administered while waiting for surgery improve outcomes.
“Basically, the study shows that you probably should keep them on antibiotics while you’re waiting,” he said.
The study was funded by Finnish Medical Foundation, the Mary and Georg Ehrnrooth Foundation, the Biomedicum Helsinki Foundation, and The Norwegian Surveillance Programme for Antimicrobial Resistance and research funds from the Finnish government. Mentula received grants from the Finnish government during the conduct of the study and personal fees from Pfizer outside the submitted work. Pappas reported no relevant disclosures.
A version of this article appeared on Medscape.com.
, according to a new study.
While the percentage of surgical site infections (SSIs) was small for both groups, patients who received antibiotics during the waiting period had lower rates of these infections.
The trial — titled PERFECT-Antibiotics — was a substudy embedded in a larger PERFECT clinical trial, which aimed to determine whether an in-hospital delay of appendectomy resulted in increased risk for appendiceal perforation when compared to emergent surgery.
The trial “concluded that appendectomy does not need to be performed promptly in acute uncomplicated appendicitis and can be scheduled within 24 hours without increasing complications,” senior author Panu Mentula, MD, of the Department of Gastroenterological Surgery, Helsinki University Hospital, Helsinki, Finland, and colleagues wrote in the study. “The next question is whether preoperatively started antibiotic treatment reduces the risk of appendiceal perforations.”
The findings were published online in JAMA Surgery on May 14, 2025.
Trial Design
PERFECT-Antibiotics was an open-label, randomized trial conducted at two hospitals in Finland and one hospital in Norway. Researchers enrolled 1774 individuals diagnosed with acute uncomplicated appendicitis, diagnosed clinically or via imaging. Patients were placed in one of two groups: The antibiotic group received intravenous (IV) cefuroxime (1500 mg) and metronidazole (500 mg) every 8 hours until surgery, while the nonantibiotic group waited for surgery without antibiotics.
All patients received one dose of IV cefuroxime (1500 mg) and metronidazole (500 mg) during anesthesia induction. The primary outcome was perforated appendicitis and secondary outcomes included complication rate and SSIs within 30 days of follow-up.
The median age of patients was 35 years (interquartile range [IQR], 28-46 years), and 55% of patients were men. Patients waited a median time of 9 hours (IQR, 4.3-15.5) from study randomization to undergoing surgery.
No Difference in Appendiceal Perforation
Of the 888 patients in the preoperative antibiotic group, 26.2% received one dose, 38.7% received two doses, 22.6% received three doses, and 11.8% received four or more doses of antibiotics, including the antibiotic dose given during anesthesia. A total of 74 patients (8.3%) in this group had a perforated appendix.
Of the 886 patients not given preoperative antibiotics, 79 (8.9%) had a perforated appendix, which met the predetermined noninferiority threshold.
The groups had similar complication rates over the 30-day follow-up, though SSIs were lower in the antibiotic group (1.6%) than the no antibiotic group (3.2%).
The researchers estimated that the number needed to treat for antibiotic therapy was 63 for SSIs, 83 for intra-abdominal SSI, and 125 for reintervention.
“Although longer preoperative antibiotic treatment resulted in slightly lower rate of postoperative infectious complications, the actual difference was very small and probably clinically not significant to justify longer preoperative antibiotic treatment,” Mentula and colleagues wrote.
Lower Infection Rates With Antibiotics
Commenting on the study for GI & Hepatology News, Theodore Pappas, MD, professor of surgery at Duke University School of Medicine in Durham, North Carolina, placed greater importance on these secondary outcomes.
Intra-abdominal infections, a subset of SSIs, were more than twice as common in the no-antibiotic group (1.9%) than in the antibiotic group (0.7%; P = .02). Positive blood cultures were also more common in the no-antibiotic group than the antibiotic group (P = .02).
While the authors qualified these results, “the reality was it was better to use antibiotics,” he said.
There was also a “big overlap between the two groups,” he said, which may have muted differences between the two groups. For example, one fourth of patients in the antibiotic group received only one dose of antibiotics, the same treatment regimen as the no-antibiotic group.
“Although protocol required prophylaxis in all patients in the induction of anesthesia, some clinicians thought that it was unnecessary, because antibiotics had already been given only a couple of hours ago” in patients in the antibiotic group, Mentula told GI & Hepatology News. She did not think that would affect the study’s results.
The PERFECT trial and the antibiotics subtrial answer two important questions that have been asked for years, Pappas continued: Whether appendectomy for uncomplicated acute appendicitis needs to be performed emergently and if antibiotics administered while waiting for surgery improve outcomes.
“Basically, the study shows that you probably should keep them on antibiotics while you’re waiting,” he said.
The study was funded by Finnish Medical Foundation, the Mary and Georg Ehrnrooth Foundation, the Biomedicum Helsinki Foundation, and The Norwegian Surveillance Programme for Antimicrobial Resistance and research funds from the Finnish government. Mentula received grants from the Finnish government during the conduct of the study and personal fees from Pfizer outside the submitted work. Pappas reported no relevant disclosures.
A version of this article appeared on Medscape.com.
, according to a new study.
While the percentage of surgical site infections (SSIs) was small for both groups, patients who received antibiotics during the waiting period had lower rates of these infections.
The trial — titled PERFECT-Antibiotics — was a substudy embedded in a larger PERFECT clinical trial, which aimed to determine whether an in-hospital delay of appendectomy resulted in increased risk for appendiceal perforation when compared to emergent surgery.
The trial “concluded that appendectomy does not need to be performed promptly in acute uncomplicated appendicitis and can be scheduled within 24 hours without increasing complications,” senior author Panu Mentula, MD, of the Department of Gastroenterological Surgery, Helsinki University Hospital, Helsinki, Finland, and colleagues wrote in the study. “The next question is whether preoperatively started antibiotic treatment reduces the risk of appendiceal perforations.”
The findings were published online in JAMA Surgery on May 14, 2025.
Trial Design
PERFECT-Antibiotics was an open-label, randomized trial conducted at two hospitals in Finland and one hospital in Norway. Researchers enrolled 1774 individuals diagnosed with acute uncomplicated appendicitis, diagnosed clinically or via imaging. Patients were placed in one of two groups: The antibiotic group received intravenous (IV) cefuroxime (1500 mg) and metronidazole (500 mg) every 8 hours until surgery, while the nonantibiotic group waited for surgery without antibiotics.
All patients received one dose of IV cefuroxime (1500 mg) and metronidazole (500 mg) during anesthesia induction. The primary outcome was perforated appendicitis and secondary outcomes included complication rate and SSIs within 30 days of follow-up.
The median age of patients was 35 years (interquartile range [IQR], 28-46 years), and 55% of patients were men. Patients waited a median time of 9 hours (IQR, 4.3-15.5) from study randomization to undergoing surgery.
No Difference in Appendiceal Perforation
Of the 888 patients in the preoperative antibiotic group, 26.2% received one dose, 38.7% received two doses, 22.6% received three doses, and 11.8% received four or more doses of antibiotics, including the antibiotic dose given during anesthesia. A total of 74 patients (8.3%) in this group had a perforated appendix.
Of the 886 patients not given preoperative antibiotics, 79 (8.9%) had a perforated appendix, which met the predetermined noninferiority threshold.
The groups had similar complication rates over the 30-day follow-up, though SSIs were lower in the antibiotic group (1.6%) than the no antibiotic group (3.2%).
The researchers estimated that the number needed to treat for antibiotic therapy was 63 for SSIs, 83 for intra-abdominal SSI, and 125 for reintervention.
“Although longer preoperative antibiotic treatment resulted in slightly lower rate of postoperative infectious complications, the actual difference was very small and probably clinically not significant to justify longer preoperative antibiotic treatment,” Mentula and colleagues wrote.
Lower Infection Rates With Antibiotics
Commenting on the study for GI & Hepatology News, Theodore Pappas, MD, professor of surgery at Duke University School of Medicine in Durham, North Carolina, placed greater importance on these secondary outcomes.
Intra-abdominal infections, a subset of SSIs, were more than twice as common in the no-antibiotic group (1.9%) than in the antibiotic group (0.7%; P = .02). Positive blood cultures were also more common in the no-antibiotic group than the antibiotic group (P = .02).
While the authors qualified these results, “the reality was it was better to use antibiotics,” he said.
There was also a “big overlap between the two groups,” he said, which may have muted differences between the two groups. For example, one fourth of patients in the antibiotic group received only one dose of antibiotics, the same treatment regimen as the no-antibiotic group.
“Although protocol required prophylaxis in all patients in the induction of anesthesia, some clinicians thought that it was unnecessary, because antibiotics had already been given only a couple of hours ago” in patients in the antibiotic group, Mentula told GI & Hepatology News. She did not think that would affect the study’s results.
The PERFECT trial and the antibiotics subtrial answer two important questions that have been asked for years, Pappas continued: Whether appendectomy for uncomplicated acute appendicitis needs to be performed emergently and if antibiotics administered while waiting for surgery improve outcomes.
“Basically, the study shows that you probably should keep them on antibiotics while you’re waiting,” he said.
The study was funded by Finnish Medical Foundation, the Mary and Georg Ehrnrooth Foundation, the Biomedicum Helsinki Foundation, and The Norwegian Surveillance Programme for Antimicrobial Resistance and research funds from the Finnish government. Mentula received grants from the Finnish government during the conduct of the study and personal fees from Pfizer outside the submitted work. Pappas reported no relevant disclosures.
A version of this article appeared on Medscape.com.