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Dear colleagues,

Lower gastrointestinal bleeding (LGIB) remains a frequent and sometimes perplexing clinical challenge. Despite advancements in endoscopic and radiologic tools, questions persist: What is the role and optimal timing of colonoscopy? How can we best utilize radiologic studies like CTA or tagged RBC scans? How should we manage patients with recurrent or intermittent bleeding that defies localization?

In this issue of Perspectives, Dr. David Wan, Dr. Fredella Lee, and Dr. Zeyad Metwalli offer their expert insights on these difficult questions. Dr. Wan, drawing on over 15 years of experience as a GI hospitalist, shares – along with his coauthor Dr. Lee – a pragmatic approach to LGIB based on clinical patterns, evolving data, and multidisciplinary collaboration. Dr. Metwalli provides the interventional radiologist’s perspective, highlighting how angiographic techniques can complement GI management and introducing novel IR strategies for patients with recurrent or elusive bleeding.

We hope their perspectives will offer valuable guidance for your practice. Join the conversation on X at @AGA_GIHN. 

Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, and chief of endoscopy at West Haven VA Medical Center, both in Connecticut. He is an associate editor for GI & Hepatology News.

Management of Lower Gastrointestinal Bleeds: GI Perspective

BY FREDELLA LEE, MD; DAVID WAN, MD

 

Acute lower gastrointestinal bleeding (LGIB) presents unique challenges. Much of this stems from the natural history of diverticular bleeding, the most common etiology of LGIB.

First, while bleeding can be severe, most will spontaneously stop. Second, despite our best efforts with imaging or colonoscopy, finding an intervenable lesion is rare. Third, LGIB has significant rates of rebleeding that are unpredictable.

While serving as a GI hospitalist for 15 years and after managing over 300 cases of LGIB, I often find myself frustrated and colonoscopy feels futile. So how can we rationally approach these patients? We will focus on three clinical questions to develop a framework for LGIB management.

• What is the role and timing for a colonoscopy?
• How do we best utilize radiologic tests?
• How can we prevent recurrent LGIB?

The Role of Colonoscopy

Traditionally, colonoscopy within 24 hours of presentation was recommended. This was based on retrospective cohort data showing higher endoscopic intervention rates and better clinical outcomes. However, this protocol requires patients to drink a significant volume of bowel preparation over a few hours (often requiring an NGT) to achieve clear rectal effluent. Moreover, one needs to mobilize a team (i.e., nurse, technician, anesthesiologist, and gastroenterologist), and find an appropriate location to scope (i.e., ED, ICU, or OR), Understandably, this is challenging, especially overnight. When the therapeutic yield is relatively low, this approach quickly loses enthusiasm.

Importantly, meta-analyses of the randomized controlled trials, have shown that urgent colonoscopies (<24 hours upon presentation), compared to elective colonoscopies (>24 hours upon presentation), do not improve clinical outcomes such as re-bleeding rates, transfusion requirements, mortality, or length of stay. In these studies, the endoscopic intervention rates were 17-34%, however, observational data shows rates of only 8%. In our practice, we will use a clear cap attachment device and water jet irrigation to increase the odds of detecting an active source of bleeding. Colonoscopy has a diagnostic yield of 95% – despite its low therapeutic yield; and while diverticular bleeds constitute up to 64% of cases, one does not want to miss colorectal cancer or other diagnoses. Regardless, there is generally no urgency to perform a colonoscopy. To quote a colleague, Dr. Elizabeth Ross, “there is no such thing as door-to-butt time.”

The Role of Radiology

Given the limits of colonoscopy, can radiographic tests such as computed tomography angiography (CTA) or tagged red blood cell (RBC) scan be helpful? Multiple studies have suggested using CTA as the initial diagnostic test. The advantages of CTAs are:

• Fast, readily available, and does not require a bowel preparation
• If negative, CTAs portend a good prognosis and make it highly unlikely to detect active extravasation on visceral angiography
• If positive, can localize the source of bleed and increase the success of intervention

Whether a positive CTA should be followed with a colonoscopy or visceral angiography remains unclear. Studies show that positive CTAs increase the detection rate of stigmata of recent hemorrhage on colonoscopy. Positive CTAs can also identify a target for embolization by interventional radiology (IR). Though an important caveat is that the success rate of embolization is highest when performed within 90 minutes of a positive CTA. This highlights that if you have IR availability, it is critical to have clear communication, a well-defined protocol, and collaboration among disciplines (i.e., ED, medical team, GI, and IR).

At our institution, we have implemented a CTA-guided protocol for severe LGIB. Those with positive CTAs are referred immediately to IR for embolization. If the embolization is unsuccessful or CTA is negative, the patient will be planned for a non-urgent inpatient colonoscopy. However, our unpublished data and other studies have shown that the overall CTA positivity rates are only between 16-22%. Moreover, one randomized controlled trial comparing CTA versus colonoscopy as an initial test did not show any meaningful difference in clinical outcomes. Thus, the benefit of CTA and the best approach to positive CTAs remains in question.

Lastly, people often ask about the utility of RBC nuclear scans. While they can detect bleeds at a slower rate (as low as 0.1 mL/min) compared to CTA (at least 0.4 mL/min), there are many limitations. RBC scans take time, are not available 24-7, and cannot precisely localize the site of bleeding. Therefore, we rarely recommend them for LGIB.

 

Approach to Recurrent Diverticular Bleeding

Unfortunately, diverticular bleeding recurs in the hospital 14% of the time and up to 25% at 5 years. When this occurs, is it worthwhile to repeat another colonoscopy or CTA?

Given the lack of clear data, we have adopted a shared decision-making framework with patients. Oftentimes, these patients are older and have significant co-morbidities, and undergoing bowel preparation, anesthesia, and colonoscopy is not trivial. If the patient is stable and prior work-up has excluded pertinent alternative diagnoses other than diverticular bleeding, then we tell patients the chance of finding an intervenable lesion is low and opt for conservative management. Meanwhile, if the patient has persistent, hemodynamically significant bleeding, we recommend a CTA based on the rationale discussed previously.

The most important clinical decision may not be about scoping or obtaining a CTA – it is medication management. If they are taking NSAIDs, they should be discontinued. If antiplatelet or anticoagulation agents were held, they should be restarted promptly in individuals with significant thrombotic risk given studies showing that while rebleeding rates may increase, overall mortality decreases.

In summary, managing LGIB and altering its natural history with either endoscopic or radiographic means is challenging. More studies are needed to guide the optimal approach. Reassuringly, most bleeding self-resolves and patients have good clinical outcomes.

Dr. Lee is a resident physician at New York Presbyterian Weill Cornell Medical Center, New York, NY. Dr. Wan is associate professor of clinical medicine at Weill Cornell Medicine, New York, N.Y. They declare no conflicts of interest.

Lower Gastrointestinal Bleeding: An Interventional Radiologist’s Perspective

BY ZEYAD METWALLI, MD, FSIR

 

When colonoscopy fails to localize and/or stop lower gastrointestinal bleeding (LGIB), catheter angiography has been commonly employed as a tool for both diagnosis and treatment of bleeding with embolization. Nuclear medicine or CT imaging studies can serve as useful adjuncts for confirming active bleeding and localizing the site of bleeding prior to angiography, particularly if this information is not provided by colonoscopy. Provocative mesenteric angiography has also become increasingly popular as a troubleshooting technique in patients with initially negative angiography.

Localization of Lower Gastrointestinal Bleeding

Radionuclide technetium-99m-lableled red blood cell scintigraphy (RBCS), also known as tagged RBC scintigraphy, has been in use since the early 1980s for investigation of acute gastrointestinal bleeding. RBCS has a high sensitivity for detection of active bleeding with a theoretical ability to detect bleeding at rates as low as 0.04-0.2 mL/minute.

Imaging protocols vary but should include dynamic images, which may aid in localization of bleeding. The relatively long half-life of the tracer used for imaging allows for delayed imaging 12 to 24 hours after injection. This can be useful to confirm active bleeding, particularly when bleeding is intermittent and is not visible on initial images. 

With the advent of computed tomography angiography (CTA), which continues to increase in speed, imaging quality and availability, the use of RBCS for evaluation of LGIB has declined. CTA is quicker to perform than RBCS and allows for detection of bleeding as well as accurate anatomic localization, which can guide interventions.

CTA provides a more comprehensive anatomic evaluation, which can aid in the diagnosis of a wide variety of intra-abdominal issues. Conversely, CTA may be less sensitive than RBCS for detection of slower acute bleeding, detecting bleeding at rates of 0.1-1 mL/min. In addition, intermittent bleeding which has temporarily stopped at the time of CTA may evade detection.

Lastly, CTA may not be appropriate in patients with impaired renal function due to risk of contrast-induced nephropathy, particularly in patients with acute kidney injury, which commonly afflicts hospitalized patients with LGIB. Prophylaxis with normal saline hydration should be employed aggressively in patients with impaired renal function, particularly when eGFR is less than 30 mL/minute. Iodinated contrast should be used judiciously in these patients.

In clinical practice, CTA and RBCS have a similar ability to confirm the presence or absence of clinically significant active gastrointestinal bleeding. Given the greater ability to rapidly localize the bleeding site with CTA, this is generally preferred over RBCS unless there is a contraindication to performing CTA, such as severe contrast allergy or high risk for development of contrast-induced nephropathy.

 

Role of Catheter Angiography and Embolization

Mesenteric angiography is a well-established technique for both detection and treatment of LGIB. Hemodynamic instability and need for packed RBC transfusion increases the likelihood of positive angiography. Limitations include reduced sensitivity for detection of bleeding slower than 0.5-1 mL/minute as well as the intermittent nature of LGIB, which will often resolve spontaneously. Angiography is variably successful in the literature with a diagnostic yield between 40-80%, which encompasses the rate of success in my own practice.

Once bleeding is identified, microcatheter placement within the feeding vessel as close as possible to the site of bleeding is important to ensure treatment efficacy and to limit risk of complications such as non-target embolization and bowel ischemia. Once the feeding vessel is selected with a microcatheter, embolization can be accomplished with a wide variety of tools including metallic coils, liquid embolic agents, and particles. In the treatment of LGIB, liquid embolic agents (e.g., n-butyl cyanoacrylate or NBCA, ethylene vinyl alcohol copolymer, etc.) and particles should be used judiciously as distal penetration increases the risk of bowel ischemia and procedure-related morbidity. For this reason, metallic coils are often preferred in the treatment of LGIB.

Although the source of bleeding is variable and may include diverticulosis, recent polypectomy, ulcer, tumor or angiodysplasia, the techniques employed are similar. Accurate and distal microcatheter selection is a key driver for successful embolization and minimizing the risk of bowel ischemia. Small intestinal bleeds can be challenging to treat due to the redundant supply of the arterial arcades supplying small bowel and may require occlusion of several branches to achieve hemostasis. This approach must be balanced with the risk of developing ischemia after embolization. Angiodysplasia, a less frequently encountered culprit of LGIB, may also be managed with selective embolization with many reports of successful treatment with liquid embolic agents such as NBCA mixed with ethiodized oil.

 

Provocative Mesenteric Angiography for Occult Bleeding

When initial angiography in a patient with suspected active LGIB is negative, provocative angiography can be considered to uncover an intermittent bleed. This may be particularly helpful in a patient where active bleeding is confirmed on a prior diagnostic test.

The approach to provocative mesenteric angiography varies by center, and a variety of agents have been used to provoke bleeding including heparin, vasodilators (i.e., nitroglycerin, verapamil, etc.) and thrombolytics (i.e., tPA), often in combination. Thrombolytics can be administered directly into the territory of interest (i.e., superior mesenteric or inferior mesenteric artery) while heparin may be administered systemically or directly into the catheterized artery. Reported success rates for provoking angiographically visible bleeding vary, but most larger series report a 40-50% success rate. The newly detected bleeding can then be treated with either embolization or surgery. A surgeon should be involved and available when provocative angiography is planned should bleeding fail to be controlled by embolization.

In summary, when colonoscopy fails to identify or control lower gastrointestinal bleeding (LGIB), imaging techniques such as RBCS and CTA play a crucial role in localizing active bleeding. While RBCS is highly sensitive, especially for intermittent or slow bleeding, CTA offers faster, more detailed anatomical information and is typically preferred unless contraindicated by renal issues or contrast allergies. Catheter-based mesenteric angiography is a well-established method for both diagnosing and treating LGIB, often using metallic coils to minimize complications like bowel ischemia. In cases where initial angiography is negative, provocative angiography – using agents like heparin or thrombolytics – may help unmask intermittent bleeding, allowing for targeted embolization or surgical intervention.

Dr. Metwalli is associate professor in the Department of Interventional Radiology, Division of Diagnostic Imaging, at The University of Texas MD Anderson Cancer Center, Houston, Texas. He declares no conflicts of interest.

Dear colleagues,

Lower gastrointestinal bleeding (LGIB) remains a frequent and sometimes perplexing clinical challenge. Despite advancements in endoscopic and radiologic tools, questions persist: What is the role and optimal timing of colonoscopy? How can we best utilize radiologic studies like CTA or tagged RBC scans? How should we manage patients with recurrent or intermittent bleeding that defies localization?

In this issue of Perspectives, Dr. David Wan, Dr. Fredella Lee, and Dr. Zeyad Metwalli offer their expert insights on these difficult questions. Dr. Wan, drawing on over 15 years of experience as a GI hospitalist, shares – along with his coauthor Dr. Lee – a pragmatic approach to LGIB based on clinical patterns, evolving data, and multidisciplinary collaboration. Dr. Metwalli provides the interventional radiologist’s perspective, highlighting how angiographic techniques can complement GI management and introducing novel IR strategies for patients with recurrent or elusive bleeding.

We hope their perspectives will offer valuable guidance for your practice. Join the conversation on X at @AGA_GIHN. 

Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, and chief of endoscopy at West Haven VA Medical Center, both in Connecticut. He is an associate editor for GI & Hepatology News.

Management of Lower Gastrointestinal Bleeds: GI Perspective

BY FREDELLA LEE, MD; DAVID WAN, MD

 

Acute lower gastrointestinal bleeding (LGIB) presents unique challenges. Much of this stems from the natural history of diverticular bleeding, the most common etiology of LGIB.

First, while bleeding can be severe, most will spontaneously stop. Second, despite our best efforts with imaging or colonoscopy, finding an intervenable lesion is rare. Third, LGIB has significant rates of rebleeding that are unpredictable.

While serving as a GI hospitalist for 15 years and after managing over 300 cases of LGIB, I often find myself frustrated and colonoscopy feels futile. So how can we rationally approach these patients? We will focus on three clinical questions to develop a framework for LGIB management.

• What is the role and timing for a colonoscopy?
• How do we best utilize radiologic tests?
• How can we prevent recurrent LGIB?

The Role of Colonoscopy

Traditionally, colonoscopy within 24 hours of presentation was recommended. This was based on retrospective cohort data showing higher endoscopic intervention rates and better clinical outcomes. However, this protocol requires patients to drink a significant volume of bowel preparation over a few hours (often requiring an NGT) to achieve clear rectal effluent. Moreover, one needs to mobilize a team (i.e., nurse, technician, anesthesiologist, and gastroenterologist), and find an appropriate location to scope (i.e., ED, ICU, or OR), Understandably, this is challenging, especially overnight. When the therapeutic yield is relatively low, this approach quickly loses enthusiasm.

Importantly, meta-analyses of the randomized controlled trials, have shown that urgent colonoscopies (<24 hours upon presentation), compared to elective colonoscopies (>24 hours upon presentation), do not improve clinical outcomes such as re-bleeding rates, transfusion requirements, mortality, or length of stay. In these studies, the endoscopic intervention rates were 17-34%, however, observational data shows rates of only 8%. In our practice, we will use a clear cap attachment device and water jet irrigation to increase the odds of detecting an active source of bleeding. Colonoscopy has a diagnostic yield of 95% – despite its low therapeutic yield; and while diverticular bleeds constitute up to 64% of cases, one does not want to miss colorectal cancer or other diagnoses. Regardless, there is generally no urgency to perform a colonoscopy. To quote a colleague, Dr. Elizabeth Ross, “there is no such thing as door-to-butt time.”

The Role of Radiology

Given the limits of colonoscopy, can radiographic tests such as computed tomography angiography (CTA) or tagged red blood cell (RBC) scan be helpful? Multiple studies have suggested using CTA as the initial diagnostic test. The advantages of CTAs are:

• Fast, readily available, and does not require a bowel preparation
• If negative, CTAs portend a good prognosis and make it highly unlikely to detect active extravasation on visceral angiography
• If positive, can localize the source of bleed and increase the success of intervention

Whether a positive CTA should be followed with a colonoscopy or visceral angiography remains unclear. Studies show that positive CTAs increase the detection rate of stigmata of recent hemorrhage on colonoscopy. Positive CTAs can also identify a target for embolization by interventional radiology (IR). Though an important caveat is that the success rate of embolization is highest when performed within 90 minutes of a positive CTA. This highlights that if you have IR availability, it is critical to have clear communication, a well-defined protocol, and collaboration among disciplines (i.e., ED, medical team, GI, and IR).

At our institution, we have implemented a CTA-guided protocol for severe LGIB. Those with positive CTAs are referred immediately to IR for embolization. If the embolization is unsuccessful or CTA is negative, the patient will be planned for a non-urgent inpatient colonoscopy. However, our unpublished data and other studies have shown that the overall CTA positivity rates are only between 16-22%. Moreover, one randomized controlled trial comparing CTA versus colonoscopy as an initial test did not show any meaningful difference in clinical outcomes. Thus, the benefit of CTA and the best approach to positive CTAs remains in question.

Lastly, people often ask about the utility of RBC nuclear scans. While they can detect bleeds at a slower rate (as low as 0.1 mL/min) compared to CTA (at least 0.4 mL/min), there are many limitations. RBC scans take time, are not available 24-7, and cannot precisely localize the site of bleeding. Therefore, we rarely recommend them for LGIB.

 

Approach to Recurrent Diverticular Bleeding

Unfortunately, diverticular bleeding recurs in the hospital 14% of the time and up to 25% at 5 years. When this occurs, is it worthwhile to repeat another colonoscopy or CTA?

Given the lack of clear data, we have adopted a shared decision-making framework with patients. Oftentimes, these patients are older and have significant co-morbidities, and undergoing bowel preparation, anesthesia, and colonoscopy is not trivial. If the patient is stable and prior work-up has excluded pertinent alternative diagnoses other than diverticular bleeding, then we tell patients the chance of finding an intervenable lesion is low and opt for conservative management. Meanwhile, if the patient has persistent, hemodynamically significant bleeding, we recommend a CTA based on the rationale discussed previously.

The most important clinical decision may not be about scoping or obtaining a CTA – it is medication management. If they are taking NSAIDs, they should be discontinued. If antiplatelet or anticoagulation agents were held, they should be restarted promptly in individuals with significant thrombotic risk given studies showing that while rebleeding rates may increase, overall mortality decreases.

In summary, managing LGIB and altering its natural history with either endoscopic or radiographic means is challenging. More studies are needed to guide the optimal approach. Reassuringly, most bleeding self-resolves and patients have good clinical outcomes.

Dr. Lee is a resident physician at New York Presbyterian Weill Cornell Medical Center, New York, NY. Dr. Wan is associate professor of clinical medicine at Weill Cornell Medicine, New York, N.Y. They declare no conflicts of interest.

Lower Gastrointestinal Bleeding: An Interventional Radiologist’s Perspective

BY ZEYAD METWALLI, MD, FSIR

 

When colonoscopy fails to localize and/or stop lower gastrointestinal bleeding (LGIB), catheter angiography has been commonly employed as a tool for both diagnosis and treatment of bleeding with embolization. Nuclear medicine or CT imaging studies can serve as useful adjuncts for confirming active bleeding and localizing the site of bleeding prior to angiography, particularly if this information is not provided by colonoscopy. Provocative mesenteric angiography has also become increasingly popular as a troubleshooting technique in patients with initially negative angiography.

Localization of Lower Gastrointestinal Bleeding

Radionuclide technetium-99m-lableled red blood cell scintigraphy (RBCS), also known as tagged RBC scintigraphy, has been in use since the early 1980s for investigation of acute gastrointestinal bleeding. RBCS has a high sensitivity for detection of active bleeding with a theoretical ability to detect bleeding at rates as low as 0.04-0.2 mL/minute.

Imaging protocols vary but should include dynamic images, which may aid in localization of bleeding. The relatively long half-life of the tracer used for imaging allows for delayed imaging 12 to 24 hours after injection. This can be useful to confirm active bleeding, particularly when bleeding is intermittent and is not visible on initial images. 

With the advent of computed tomography angiography (CTA), which continues to increase in speed, imaging quality and availability, the use of RBCS for evaluation of LGIB has declined. CTA is quicker to perform than RBCS and allows for detection of bleeding as well as accurate anatomic localization, which can guide interventions.

CTA provides a more comprehensive anatomic evaluation, which can aid in the diagnosis of a wide variety of intra-abdominal issues. Conversely, CTA may be less sensitive than RBCS for detection of slower acute bleeding, detecting bleeding at rates of 0.1-1 mL/min. In addition, intermittent bleeding which has temporarily stopped at the time of CTA may evade detection.

Lastly, CTA may not be appropriate in patients with impaired renal function due to risk of contrast-induced nephropathy, particularly in patients with acute kidney injury, which commonly afflicts hospitalized patients with LGIB. Prophylaxis with normal saline hydration should be employed aggressively in patients with impaired renal function, particularly when eGFR is less than 30 mL/minute. Iodinated contrast should be used judiciously in these patients.

In clinical practice, CTA and RBCS have a similar ability to confirm the presence or absence of clinically significant active gastrointestinal bleeding. Given the greater ability to rapidly localize the bleeding site with CTA, this is generally preferred over RBCS unless there is a contraindication to performing CTA, such as severe contrast allergy or high risk for development of contrast-induced nephropathy.

 

Role of Catheter Angiography and Embolization

Mesenteric angiography is a well-established technique for both detection and treatment of LGIB. Hemodynamic instability and need for packed RBC transfusion increases the likelihood of positive angiography. Limitations include reduced sensitivity for detection of bleeding slower than 0.5-1 mL/minute as well as the intermittent nature of LGIB, which will often resolve spontaneously. Angiography is variably successful in the literature with a diagnostic yield between 40-80%, which encompasses the rate of success in my own practice.

Once bleeding is identified, microcatheter placement within the feeding vessel as close as possible to the site of bleeding is important to ensure treatment efficacy and to limit risk of complications such as non-target embolization and bowel ischemia. Once the feeding vessel is selected with a microcatheter, embolization can be accomplished with a wide variety of tools including metallic coils, liquid embolic agents, and particles. In the treatment of LGIB, liquid embolic agents (e.g., n-butyl cyanoacrylate or NBCA, ethylene vinyl alcohol copolymer, etc.) and particles should be used judiciously as distal penetration increases the risk of bowel ischemia and procedure-related morbidity. For this reason, metallic coils are often preferred in the treatment of LGIB.

Although the source of bleeding is variable and may include diverticulosis, recent polypectomy, ulcer, tumor or angiodysplasia, the techniques employed are similar. Accurate and distal microcatheter selection is a key driver for successful embolization and minimizing the risk of bowel ischemia. Small intestinal bleeds can be challenging to treat due to the redundant supply of the arterial arcades supplying small bowel and may require occlusion of several branches to achieve hemostasis. This approach must be balanced with the risk of developing ischemia after embolization. Angiodysplasia, a less frequently encountered culprit of LGIB, may also be managed with selective embolization with many reports of successful treatment with liquid embolic agents such as NBCA mixed with ethiodized oil.

 

Provocative Mesenteric Angiography for Occult Bleeding

When initial angiography in a patient with suspected active LGIB is negative, provocative angiography can be considered to uncover an intermittent bleed. This may be particularly helpful in a patient where active bleeding is confirmed on a prior diagnostic test.

The approach to provocative mesenteric angiography varies by center, and a variety of agents have been used to provoke bleeding including heparin, vasodilators (i.e., nitroglycerin, verapamil, etc.) and thrombolytics (i.e., tPA), often in combination. Thrombolytics can be administered directly into the territory of interest (i.e., superior mesenteric or inferior mesenteric artery) while heparin may be administered systemically or directly into the catheterized artery. Reported success rates for provoking angiographically visible bleeding vary, but most larger series report a 40-50% success rate. The newly detected bleeding can then be treated with either embolization or surgery. A surgeon should be involved and available when provocative angiography is planned should bleeding fail to be controlled by embolization.

In summary, when colonoscopy fails to identify or control lower gastrointestinal bleeding (LGIB), imaging techniques such as RBCS and CTA play a crucial role in localizing active bleeding. While RBCS is highly sensitive, especially for intermittent or slow bleeding, CTA offers faster, more detailed anatomical information and is typically preferred unless contraindicated by renal issues or contrast allergies. Catheter-based mesenteric angiography is a well-established method for both diagnosing and treating LGIB, often using metallic coils to minimize complications like bowel ischemia. In cases where initial angiography is negative, provocative angiography – using agents like heparin or thrombolytics – may help unmask intermittent bleeding, allowing for targeted embolization or surgical intervention.

Dr. Metwalli is associate professor in the Department of Interventional Radiology, Division of Diagnostic Imaging, at The University of Texas MD Anderson Cancer Center, Houston, Texas. He declares no conflicts of interest.

Dear colleagues,

Lower gastrointestinal bleeding (LGIB) remains a frequent and sometimes perplexing clinical challenge. Despite advancements in endoscopic and radiologic tools, questions persist: What is the role and optimal timing of colonoscopy? How can we best utilize radiologic studies like CTA or tagged RBC scans? How should we manage patients with recurrent or intermittent bleeding that defies localization?

In this issue of Perspectives, Dr. David Wan, Dr. Fredella Lee, and Dr. Zeyad Metwalli offer their expert insights on these difficult questions. Dr. Wan, drawing on over 15 years of experience as a GI hospitalist, shares – along with his coauthor Dr. Lee – a pragmatic approach to LGIB based on clinical patterns, evolving data, and multidisciplinary collaboration. Dr. Metwalli provides the interventional radiologist’s perspective, highlighting how angiographic techniques can complement GI management and introducing novel IR strategies for patients with recurrent or elusive bleeding.

We hope their perspectives will offer valuable guidance for your practice. Join the conversation on X at @AGA_GIHN. 

Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, and chief of endoscopy at West Haven VA Medical Center, both in Connecticut. He is an associate editor for GI & Hepatology News.

Management of Lower Gastrointestinal Bleeds: GI Perspective

BY FREDELLA LEE, MD; DAVID WAN, MD

 

Acute lower gastrointestinal bleeding (LGIB) presents unique challenges. Much of this stems from the natural history of diverticular bleeding, the most common etiology of LGIB.

First, while bleeding can be severe, most will spontaneously stop. Second, despite our best efforts with imaging or colonoscopy, finding an intervenable lesion is rare. Third, LGIB has significant rates of rebleeding that are unpredictable.

While serving as a GI hospitalist for 15 years and after managing over 300 cases of LGIB, I often find myself frustrated and colonoscopy feels futile. So how can we rationally approach these patients? We will focus on three clinical questions to develop a framework for LGIB management.

• What is the role and timing for a colonoscopy?
• How do we best utilize radiologic tests?
• How can we prevent recurrent LGIB?

The Role of Colonoscopy

Traditionally, colonoscopy within 24 hours of presentation was recommended. This was based on retrospective cohort data showing higher endoscopic intervention rates and better clinical outcomes. However, this protocol requires patients to drink a significant volume of bowel preparation over a few hours (often requiring an NGT) to achieve clear rectal effluent. Moreover, one needs to mobilize a team (i.e., nurse, technician, anesthesiologist, and gastroenterologist), and find an appropriate location to scope (i.e., ED, ICU, or OR), Understandably, this is challenging, especially overnight. When the therapeutic yield is relatively low, this approach quickly loses enthusiasm.

Importantly, meta-analyses of the randomized controlled trials, have shown that urgent colonoscopies (<24 hours upon presentation), compared to elective colonoscopies (>24 hours upon presentation), do not improve clinical outcomes such as re-bleeding rates, transfusion requirements, mortality, or length of stay. In these studies, the endoscopic intervention rates were 17-34%, however, observational data shows rates of only 8%. In our practice, we will use a clear cap attachment device and water jet irrigation to increase the odds of detecting an active source of bleeding. Colonoscopy has a diagnostic yield of 95% – despite its low therapeutic yield; and while diverticular bleeds constitute up to 64% of cases, one does not want to miss colorectal cancer or other diagnoses. Regardless, there is generally no urgency to perform a colonoscopy. To quote a colleague, Dr. Elizabeth Ross, “there is no such thing as door-to-butt time.”

The Role of Radiology

Given the limits of colonoscopy, can radiographic tests such as computed tomography angiography (CTA) or tagged red blood cell (RBC) scan be helpful? Multiple studies have suggested using CTA as the initial diagnostic test. The advantages of CTAs are:

• Fast, readily available, and does not require a bowel preparation
• If negative, CTAs portend a good prognosis and make it highly unlikely to detect active extravasation on visceral angiography
• If positive, can localize the source of bleed and increase the success of intervention

Whether a positive CTA should be followed with a colonoscopy or visceral angiography remains unclear. Studies show that positive CTAs increase the detection rate of stigmata of recent hemorrhage on colonoscopy. Positive CTAs can also identify a target for embolization by interventional radiology (IR). Though an important caveat is that the success rate of embolization is highest when performed within 90 minutes of a positive CTA. This highlights that if you have IR availability, it is critical to have clear communication, a well-defined protocol, and collaboration among disciplines (i.e., ED, medical team, GI, and IR).

At our institution, we have implemented a CTA-guided protocol for severe LGIB. Those with positive CTAs are referred immediately to IR for embolization. If the embolization is unsuccessful or CTA is negative, the patient will be planned for a non-urgent inpatient colonoscopy. However, our unpublished data and other studies have shown that the overall CTA positivity rates are only between 16-22%. Moreover, one randomized controlled trial comparing CTA versus colonoscopy as an initial test did not show any meaningful difference in clinical outcomes. Thus, the benefit of CTA and the best approach to positive CTAs remains in question.

Lastly, people often ask about the utility of RBC nuclear scans. While they can detect bleeds at a slower rate (as low as 0.1 mL/min) compared to CTA (at least 0.4 mL/min), there are many limitations. RBC scans take time, are not available 24-7, and cannot precisely localize the site of bleeding. Therefore, we rarely recommend them for LGIB.

 

Approach to Recurrent Diverticular Bleeding

Unfortunately, diverticular bleeding recurs in the hospital 14% of the time and up to 25% at 5 years. When this occurs, is it worthwhile to repeat another colonoscopy or CTA?

Given the lack of clear data, we have adopted a shared decision-making framework with patients. Oftentimes, these patients are older and have significant co-morbidities, and undergoing bowel preparation, anesthesia, and colonoscopy is not trivial. If the patient is stable and prior work-up has excluded pertinent alternative diagnoses other than diverticular bleeding, then we tell patients the chance of finding an intervenable lesion is low and opt for conservative management. Meanwhile, if the patient has persistent, hemodynamically significant bleeding, we recommend a CTA based on the rationale discussed previously.

The most important clinical decision may not be about scoping or obtaining a CTA – it is medication management. If they are taking NSAIDs, they should be discontinued. If antiplatelet or anticoagulation agents were held, they should be restarted promptly in individuals with significant thrombotic risk given studies showing that while rebleeding rates may increase, overall mortality decreases.

In summary, managing LGIB and altering its natural history with either endoscopic or radiographic means is challenging. More studies are needed to guide the optimal approach. Reassuringly, most bleeding self-resolves and patients have good clinical outcomes.

Dr. Lee is a resident physician at New York Presbyterian Weill Cornell Medical Center, New York, NY. Dr. Wan is associate professor of clinical medicine at Weill Cornell Medicine, New York, N.Y. They declare no conflicts of interest.

Lower Gastrointestinal Bleeding: An Interventional Radiologist’s Perspective

BY ZEYAD METWALLI, MD, FSIR

 

When colonoscopy fails to localize and/or stop lower gastrointestinal bleeding (LGIB), catheter angiography has been commonly employed as a tool for both diagnosis and treatment of bleeding with embolization. Nuclear medicine or CT imaging studies can serve as useful adjuncts for confirming active bleeding and localizing the site of bleeding prior to angiography, particularly if this information is not provided by colonoscopy. Provocative mesenteric angiography has also become increasingly popular as a troubleshooting technique in patients with initially negative angiography.

Localization of Lower Gastrointestinal Bleeding

Radionuclide technetium-99m-lableled red blood cell scintigraphy (RBCS), also known as tagged RBC scintigraphy, has been in use since the early 1980s for investigation of acute gastrointestinal bleeding. RBCS has a high sensitivity for detection of active bleeding with a theoretical ability to detect bleeding at rates as low as 0.04-0.2 mL/minute.

Imaging protocols vary but should include dynamic images, which may aid in localization of bleeding. The relatively long half-life of the tracer used for imaging allows for delayed imaging 12 to 24 hours after injection. This can be useful to confirm active bleeding, particularly when bleeding is intermittent and is not visible on initial images. 

With the advent of computed tomography angiography (CTA), which continues to increase in speed, imaging quality and availability, the use of RBCS for evaluation of LGIB has declined. CTA is quicker to perform than RBCS and allows for detection of bleeding as well as accurate anatomic localization, which can guide interventions.

CTA provides a more comprehensive anatomic evaluation, which can aid in the diagnosis of a wide variety of intra-abdominal issues. Conversely, CTA may be less sensitive than RBCS for detection of slower acute bleeding, detecting bleeding at rates of 0.1-1 mL/min. In addition, intermittent bleeding which has temporarily stopped at the time of CTA may evade detection.

Lastly, CTA may not be appropriate in patients with impaired renal function due to risk of contrast-induced nephropathy, particularly in patients with acute kidney injury, which commonly afflicts hospitalized patients with LGIB. Prophylaxis with normal saline hydration should be employed aggressively in patients with impaired renal function, particularly when eGFR is less than 30 mL/minute. Iodinated contrast should be used judiciously in these patients.

In clinical practice, CTA and RBCS have a similar ability to confirm the presence or absence of clinically significant active gastrointestinal bleeding. Given the greater ability to rapidly localize the bleeding site with CTA, this is generally preferred over RBCS unless there is a contraindication to performing CTA, such as severe contrast allergy or high risk for development of contrast-induced nephropathy.

 

Role of Catheter Angiography and Embolization

Mesenteric angiography is a well-established technique for both detection and treatment of LGIB. Hemodynamic instability and need for packed RBC transfusion increases the likelihood of positive angiography. Limitations include reduced sensitivity for detection of bleeding slower than 0.5-1 mL/minute as well as the intermittent nature of LGIB, which will often resolve spontaneously. Angiography is variably successful in the literature with a diagnostic yield between 40-80%, which encompasses the rate of success in my own practice.

Once bleeding is identified, microcatheter placement within the feeding vessel as close as possible to the site of bleeding is important to ensure treatment efficacy and to limit risk of complications such as non-target embolization and bowel ischemia. Once the feeding vessel is selected with a microcatheter, embolization can be accomplished with a wide variety of tools including metallic coils, liquid embolic agents, and particles. In the treatment of LGIB, liquid embolic agents (e.g., n-butyl cyanoacrylate or NBCA, ethylene vinyl alcohol copolymer, etc.) and particles should be used judiciously as distal penetration increases the risk of bowel ischemia and procedure-related morbidity. For this reason, metallic coils are often preferred in the treatment of LGIB.

Although the source of bleeding is variable and may include diverticulosis, recent polypectomy, ulcer, tumor or angiodysplasia, the techniques employed are similar. Accurate and distal microcatheter selection is a key driver for successful embolization and minimizing the risk of bowel ischemia. Small intestinal bleeds can be challenging to treat due to the redundant supply of the arterial arcades supplying small bowel and may require occlusion of several branches to achieve hemostasis. This approach must be balanced with the risk of developing ischemia after embolization. Angiodysplasia, a less frequently encountered culprit of LGIB, may also be managed with selective embolization with many reports of successful treatment with liquid embolic agents such as NBCA mixed with ethiodized oil.

 

Provocative Mesenteric Angiography for Occult Bleeding

When initial angiography in a patient with suspected active LGIB is negative, provocative angiography can be considered to uncover an intermittent bleed. This may be particularly helpful in a patient where active bleeding is confirmed on a prior diagnostic test.

The approach to provocative mesenteric angiography varies by center, and a variety of agents have been used to provoke bleeding including heparin, vasodilators (i.e., nitroglycerin, verapamil, etc.) and thrombolytics (i.e., tPA), often in combination. Thrombolytics can be administered directly into the territory of interest (i.e., superior mesenteric or inferior mesenteric artery) while heparin may be administered systemically or directly into the catheterized artery. Reported success rates for provoking angiographically visible bleeding vary, but most larger series report a 40-50% success rate. The newly detected bleeding can then be treated with either embolization or surgery. A surgeon should be involved and available when provocative angiography is planned should bleeding fail to be controlled by embolization.

In summary, when colonoscopy fails to identify or control lower gastrointestinal bleeding (LGIB), imaging techniques such as RBCS and CTA play a crucial role in localizing active bleeding. While RBCS is highly sensitive, especially for intermittent or slow bleeding, CTA offers faster, more detailed anatomical information and is typically preferred unless contraindicated by renal issues or contrast allergies. Catheter-based mesenteric angiography is a well-established method for both diagnosing and treating LGIB, often using metallic coils to minimize complications like bowel ischemia. In cases where initial angiography is negative, provocative angiography – using agents like heparin or thrombolytics – may help unmask intermittent bleeding, allowing for targeted embolization or surgical intervention.

Dr. Metwalli is associate professor in the Department of Interventional Radiology, Division of Diagnostic Imaging, at The University of Texas MD Anderson Cancer Center, Houston, Texas. He declares no conflicts of interest.

Introduction: Cases

Patient 1: A 57-year-old man with post-prandial distress variant functional dyspepsia (FD) was recommended to start nortriptyline. He previously established primary care with a physician he met at a barbershop health fair in Harlem, who referred him for specialty evaluation. Today, he presents for follow-up and reports he did not take this medication because he heard it is an antidepressant. How would you counsel him? 

Patient 2: A 61-year-old woman was previously diagnosed with mixed variant irritable bowel syndrome (IBS-M). Her symptoms have not significantly changed. Her prior workup has been reassuring and consistent with IBS-M. Despite this, the patient pushes to repeat a colonoscopy, fearful that something is being missed or that she is not being offered care because of her undocumented status. How do you respond? 

Patient 3: A 36-year-old man is followed for the management of generalized anxiety disorder and functional heartburn. He was started on low-dose amitriptyline with some benefit, but follow-up has been sporadic. On further discussion, he reports financial stressors, time barriers, and difficulty scheduling a meeting with his union representative for work accommodations as he lives in a more rural community. How do you reply?

Patient 4: A 74-year-old man with Parkinson’s disease who uses a wheelchair has functional constipation that is well controlled on his current regimen. He has never undergone colon cancer screening. He occasionally notices blood in his stool, so a colonoscopy was recommended to confirm that his hematochezia reflects functional constipation complicated by hemorrhoids. He is concerned about the bowel preparation required for a colonoscopy given his limited mobility, as his insurance does not cover assistance at home. He does not have family members to help him. How can you assist him?

Social determinants of health, health disparities, and DGBIs

Social determinants of health affect all aspects of patient care, with an increasing body of published work looking at potential disparities in organ-based and structural diseases.^1,2,3,4 However, little has been done to explore their influence on disorders of gut-brain interaction or DGBIs.

From a pathophysiologic perspective, the impact of biopsychosocial stressors is particularly relevant in patients with DGBIs. As DGBIs cannot be diagnosed with a single laboratory or endoscopic test, the patient history is of the utmost importance and physician-patient rapport is paramount in their treatment. Such rapport may be more difficult to establish in patients coming from historically marginalized and minoritized communities who may be distrustful of healthcare as an institution of (discriminatory) power. 

 

Potential DGBI management pitfalls in historically marginalized or minoritized communities

For racial and ethnic minorities in the United States, disparities in healthcare take on many forms. People from racial and ethnic minority communities are less likely to receive a gastroenterology consultation and those with IBS are more likely to undergo procedures as compared to White patients with IBS.⁶ Implicit bias may lead to fewer specialist referrals, and specialty care may be limited or unavailable in some areas. Patients may prefer seeing providers in their own community, with whom they share racial or ethnic identities, which could lead to fewer referrals to specialists outside of the community.

Historical discrimination contributes to a lack of trust in healthcare professionals, which may lead patients to favor more objective diagnostics such as endoscopy or view being counseled against invasive procedures as having necessary care denied. Due to a broader cultural stigma surrounding mental illness, patients may be more hesitant to utilize neuromodulators, which have historically been used for psychiatric diagnoses, as it may lead them to conflate their GI illness with mental illness.^7,8

Since DGBIs cannot be diagnosed with a single test or managed with a single treatment modality, providing excellent care for patients with DGBIs requires clear communication. For patients with limited English proficiency (LEP), access to high-quality language assistance is the foundation of comprehensive care. Interpreter use (or lack thereof) may limit the ability to obtain a complete and accurate clinical history, which can lead to fewer referrals to specialists and increased reliance on endoscopic evaluations that may not be clinically indicated.

These language barriers affect patients on many levels – in their ability to understand instructions for medication administration, preparation for procedures, and return precautions – which may ultimately lead to poorer responses to therapy or delays in care. LEP alone is broadly associated with fewer referrals for outpatient follow-up, adverse health outcomes and complications, and longer hospital stays.⁹ These disparities can be mitigated by investing in high-quality interpreter services, providing instructions and forms in multiple languages, and engaging the patient’s family and social supports according to their preferences.

People experiencing poverty (urban and rural) face challenges across multiple domains including access to healthcare, health insurance, stable housing and employment, and more. Many patients seek care at federally qualified health centers, which may face greater difficulties coordinating care with external gastroenterologists.¹⁰

 

Insurance barriers limit access to essential medications, tests, and procedures, and create delays in establishing care with specialists. Significant psychological stress and higher rates of comorbid anxiety and depression contribute to increased IBS severity.¹¹ Financial limitations may limit dietary choices, which can further exacerbate DGBI symptoms. Long work hours with limited flexibility may prohibit them from presenting for regular follow-ups and establishing advanced DGBI care such as with a dietitian or psychologist.

Patients with disabilities face many of the health inequities previously discussed, as well as additional challenges with physical accessibility, transportation, exclusion from education and employment, discrimination, and stigma. Higher prevalence of comorbid mental illness and higher rates of intimate partner violence and interpersonal violence all contribute to DGBI severity and challenges with access to care.^12,13 Patients with disabilities may struggle to arrive at appointments, maneuver through the building or exam room, and ultimately follow recommended care plans.

 

How to approach DGBIs in historically marginalized and minoritized communities

Returning to the patients from the introduction, how would you counsel each of them?

Patient 1: We can discuss with the patient how nortriptyline and other typical antidepressants can and often are used for indications other than depression. These medications modify centrally-mediated pain signaling and many patients with functional dyspepsia experience a significant benefit. It is critical to build on the rapport that was established at the community health outreach event and to explore the patient’s concerns thoroughly.

Patient 2: We would begin by inquiring about her underlying fears associated with her symptoms and seek to understand her goals for repeat intervention. We can review the risks of endoscopy and shift the focus to improving her symptoms. If we can improve her bowel habits or her pain, her desire for further interventions may lessen. 

Patient 3: It will be important to work within the realistic time and monetary constraints in this patient’s life. We can validate him and the challenges he is facing, provide positive reinforcement for the progress he has made so far, and avoid disparaging him for the aspects of the treatment plan he has been unable to follow through with. As he reported a benefit from amitriptyline, we can consider increasing his dose as a feasible next step. 

Patient 4: We can encourage the patient to discuss with his primary care physician how they may be able to coordinate an inpatient admission for colonoscopy preparation. Given his co-morbidities, this avenue will provide him dedicated support to help him adequately prep to ensure a higher quality examination and limit the need for repeat procedures.

DGBI care in historically marginalized and minoritized communities: A call to action

Understanding cultural differences and existing disparities in care is essential to improving care for patients from historically minoritized communities with DGBIs. Motivational interviewing and shared decision-making, with acknowledgment of social and cultural differences, allow us to work together with patients and their support systems to set and achieve feasible goals.¹⁴

 

To address known health disparities, offices can take steps to ensure the accessibility of language, forms, physical space, providers, and care teams. Providing culturally sensitive care and lowering barriers to care are the first steps to effecting meaningful change for patients with DGBIs from historically minoritized communities.

Dr. Yu is based at Division of Gastroenterology and Hepatology, Boston Medical Center and Boston University, both in Boston, Massachusetts. Dr. Dimino and Dr. Vélez are based at the Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, both in Boston, Massachusetts. Dr. Yu, Dr. Dimino, and Dr. Vélez do not have any conflicts of interest for this article.

Additional Online Resources

Form Accessibility 

• Intake Form Guidance for Providers
• Making Your Clinic Welcoming to LGBTQ Patients
• Transgender data collection in the electronic health record: Current concepts and issues

Language Accessibility 

• Overcoming the challenges of providing care to limited English proficient patients

Physical Accessibility 

• Access to Medical Care for Individuals with Mobility Disabilities
• Making your medical office accessible

References

1. Zavala VA, et al. Cancer health disparities in racial/ethnic minorities in the United States. Br J Cancer. 2021 Jan. doi: 10.1038/s41416-020-01038-6.

2. Kardashian A, et al. Health disparities in chronic liver disease. Hepatology. 2023 Apr. doi: 10.1002/hep.32743.

3. Nephew LD, Serper M. Racial, Gender, and Socioeconomic Disparities in Liver Transplantation. Liver Transpl. 2021 Jun. doi: 10.1002/lt.25996.

4. Anyane-Yeboa A, et al. The Impact of the Social Determinants of Health on Disparities in Inflammatory Bowel Disease. Clin Gastroenterol Hepatol. 2022 Nov. doi: 10.1016/j.cgh.2022.03.011.

5. Drossman DA. Functional Gastrointestinal Disorders: History, Pathophysiology, Clinical Features and Rome IV. Gastroenterology. 2016 Feb. doi: 10.1053/j.gastro.2016.02.032.

6. Silvernale C, et al. Racial disparity in healthcare utilization among patients with Irritable Bowel Syndrome: results from a multicenter cohort. Neurogastroenterol Motil. 2021 May. doi: 10.1111/nmo.14039.

7. Hearn M, et al. Stigma and irritable bowel syndrome: a taboo subject? Lancet Gastroenterol Hepatol. 2020 Jun. doi: 10.1016/S2468-1253(19)30348-6.

8. Yan XJ, et al. The impact of stigma on medication adherence in patients with functional dyspepsia. Neurogastroenterol Motil. 2021 Feb. doi: 10.1111/nmo.13956.

9. Twersky SE, et al. The Impact of Limited English Proficiency on Healthcare Access and Outcomes in the U.S.: A Scoping Review. Healthcare (Basel). 2024 Jan. doi: 10.3390/healthcare12030364.

10. Bayly JE, et al. Limited English proficiency and reported receipt of colorectal cancer screening among adults 45-75 in 2019 and 2021. Prev Med Rep. 2024 Feb. doi: 10.1016/j.pmedr.2024.102638.

11. Cheng K, et al. Epidemiology of Irritable Bowel Syndrome in a Large Academic Safety-Net Hospital. J Clin Med. 2024 Feb. doi: 10.3390/jcm13051314.

12. Breiding MJ, Armour BS. The association between disability and intimate partner violence in the United States. Ann Epidemiol. 2015 Jun. doi: 10.1016/j.annepidem.2015.03.017.

13. Mitra M, et al. Prevalence and characteristics of sexual violence against men with disabilities. Am J Prev Med. 2016 Mar. doi: 10.1016/j.amepre.2015.07.030.

14. Bahafzallah L, et al. Motivational Interviewing in Ethnic Populations. J Immigr Minor Health. 2020 Aug. doi: 10.1007/s10903-019-00940-3.

Introduction: Cases

Patient 1: A 57-year-old man with post-prandial distress variant functional dyspepsia (FD) was recommended to start nortriptyline. He previously established primary care with a physician he met at a barbershop health fair in Harlem, who referred him for specialty evaluation. Today, he presents for follow-up and reports he did not take this medication because he heard it is an antidepressant. How would you counsel him? 

Patient 2: A 61-year-old woman was previously diagnosed with mixed variant irritable bowel syndrome (IBS-M). Her symptoms have not significantly changed. Her prior workup has been reassuring and consistent with IBS-M. Despite this, the patient pushes to repeat a colonoscopy, fearful that something is being missed or that she is not being offered care because of her undocumented status. How do you respond? 

Patient 3: A 36-year-old man is followed for the management of generalized anxiety disorder and functional heartburn. He was started on low-dose amitriptyline with some benefit, but follow-up has been sporadic. On further discussion, he reports financial stressors, time barriers, and difficulty scheduling a meeting with his union representative for work accommodations as he lives in a more rural community. How do you reply?

Patient 4: A 74-year-old man with Parkinson’s disease who uses a wheelchair has functional constipation that is well controlled on his current regimen. He has never undergone colon cancer screening. He occasionally notices blood in his stool, so a colonoscopy was recommended to confirm that his hematochezia reflects functional constipation complicated by hemorrhoids. He is concerned about the bowel preparation required for a colonoscopy given his limited mobility, as his insurance does not cover assistance at home. He does not have family members to help him. How can you assist him?

Social determinants of health, health disparities, and DGBIs

Social determinants of health affect all aspects of patient care, with an increasing body of published work looking at potential disparities in organ-based and structural diseases.^1,2,3,4 However, little has been done to explore their influence on disorders of gut-brain interaction or DGBIs.

From a pathophysiologic perspective, the impact of biopsychosocial stressors is particularly relevant in patients with DGBIs. As DGBIs cannot be diagnosed with a single laboratory or endoscopic test, the patient history is of the utmost importance and physician-patient rapport is paramount in their treatment. Such rapport may be more difficult to establish in patients coming from historically marginalized and minoritized communities who may be distrustful of healthcare as an institution of (discriminatory) power. 

 

Potential DGBI management pitfalls in historically marginalized or minoritized communities

For racial and ethnic minorities in the United States, disparities in healthcare take on many forms. People from racial and ethnic minority communities are less likely to receive a gastroenterology consultation and those with IBS are more likely to undergo procedures as compared to White patients with IBS.⁶ Implicit bias may lead to fewer specialist referrals, and specialty care may be limited or unavailable in some areas. Patients may prefer seeing providers in their own community, with whom they share racial or ethnic identities, which could lead to fewer referrals to specialists outside of the community.

Historical discrimination contributes to a lack of trust in healthcare professionals, which may lead patients to favor more objective diagnostics such as endoscopy or view being counseled against invasive procedures as having necessary care denied. Due to a broader cultural stigma surrounding mental illness, patients may be more hesitant to utilize neuromodulators, which have historically been used for psychiatric diagnoses, as it may lead them to conflate their GI illness with mental illness.^7,8

Since DGBIs cannot be diagnosed with a single test or managed with a single treatment modality, providing excellent care for patients with DGBIs requires clear communication. For patients with limited English proficiency (LEP), access to high-quality language assistance is the foundation of comprehensive care. Interpreter use (or lack thereof) may limit the ability to obtain a complete and accurate clinical history, which can lead to fewer referrals to specialists and increased reliance on endoscopic evaluations that may not be clinically indicated.

These language barriers affect patients on many levels – in their ability to understand instructions for medication administration, preparation for procedures, and return precautions – which may ultimately lead to poorer responses to therapy or delays in care. LEP alone is broadly associated with fewer referrals for outpatient follow-up, adverse health outcomes and complications, and longer hospital stays.⁹ These disparities can be mitigated by investing in high-quality interpreter services, providing instructions and forms in multiple languages, and engaging the patient’s family and social supports according to their preferences.

People experiencing poverty (urban and rural) face challenges across multiple domains including access to healthcare, health insurance, stable housing and employment, and more. Many patients seek care at federally qualified health centers, which may face greater difficulties coordinating care with external gastroenterologists.¹⁰

 

Insurance barriers limit access to essential medications, tests, and procedures, and create delays in establishing care with specialists. Significant psychological stress and higher rates of comorbid anxiety and depression contribute to increased IBS severity.¹¹ Financial limitations may limit dietary choices, which can further exacerbate DGBI symptoms. Long work hours with limited flexibility may prohibit them from presenting for regular follow-ups and establishing advanced DGBI care such as with a dietitian or psychologist.

Patients with disabilities face many of the health inequities previously discussed, as well as additional challenges with physical accessibility, transportation, exclusion from education and employment, discrimination, and stigma. Higher prevalence of comorbid mental illness and higher rates of intimate partner violence and interpersonal violence all contribute to DGBI severity and challenges with access to care.^12,13 Patients with disabilities may struggle to arrive at appointments, maneuver through the building or exam room, and ultimately follow recommended care plans.

 

How to approach DGBIs in historically marginalized and minoritized communities

Returning to the patients from the introduction, how would you counsel each of them?

Patient 1: We can discuss with the patient how nortriptyline and other typical antidepressants can and often are used for indications other than depression. These medications modify centrally-mediated pain signaling and many patients with functional dyspepsia experience a significant benefit. It is critical to build on the rapport that was established at the community health outreach event and to explore the patient’s concerns thoroughly.

Patient 2: We would begin by inquiring about her underlying fears associated with her symptoms and seek to understand her goals for repeat intervention. We can review the risks of endoscopy and shift the focus to improving her symptoms. If we can improve her bowel habits or her pain, her desire for further interventions may lessen. 

Patient 3: It will be important to work within the realistic time and monetary constraints in this patient’s life. We can validate him and the challenges he is facing, provide positive reinforcement for the progress he has made so far, and avoid disparaging him for the aspects of the treatment plan he has been unable to follow through with. As he reported a benefit from amitriptyline, we can consider increasing his dose as a feasible next step. 

Patient 4: We can encourage the patient to discuss with his primary care physician how they may be able to coordinate an inpatient admission for colonoscopy preparation. Given his co-morbidities, this avenue will provide him dedicated support to help him adequately prep to ensure a higher quality examination and limit the need for repeat procedures.

DGBI care in historically marginalized and minoritized communities: A call to action

Understanding cultural differences and existing disparities in care is essential to improving care for patients from historically minoritized communities with DGBIs. Motivational interviewing and shared decision-making, with acknowledgment of social and cultural differences, allow us to work together with patients and their support systems to set and achieve feasible goals.¹⁴

 

To address known health disparities, offices can take steps to ensure the accessibility of language, forms, physical space, providers, and care teams. Providing culturally sensitive care and lowering barriers to care are the first steps to effecting meaningful change for patients with DGBIs from historically minoritized communities.

Dr. Yu is based at Division of Gastroenterology and Hepatology, Boston Medical Center and Boston University, both in Boston, Massachusetts. Dr. Dimino and Dr. Vélez are based at the Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, both in Boston, Massachusetts. Dr. Yu, Dr. Dimino, and Dr. Vélez do not have any conflicts of interest for this article.

Additional Online Resources

Form Accessibility 

• Intake Form Guidance for Providers
• Making Your Clinic Welcoming to LGBTQ Patients
• Transgender data collection in the electronic health record: Current concepts and issues

Language Accessibility 

• Overcoming the challenges of providing care to limited English proficient patients

Physical Accessibility 

• Access to Medical Care for Individuals with Mobility Disabilities
• Making your medical office accessible

References

1. Zavala VA, et al. Cancer health disparities in racial/ethnic minorities in the United States. Br J Cancer. 2021 Jan. doi: 10.1038/s41416-020-01038-6.

2. Kardashian A, et al. Health disparities in chronic liver disease. Hepatology. 2023 Apr. doi: 10.1002/hep.32743.

3. Nephew LD, Serper M. Racial, Gender, and Socioeconomic Disparities in Liver Transplantation. Liver Transpl. 2021 Jun. doi: 10.1002/lt.25996.

4. Anyane-Yeboa A, et al. The Impact of the Social Determinants of Health on Disparities in Inflammatory Bowel Disease. Clin Gastroenterol Hepatol. 2022 Nov. doi: 10.1016/j.cgh.2022.03.011.

5. Drossman DA. Functional Gastrointestinal Disorders: History, Pathophysiology, Clinical Features and Rome IV. Gastroenterology. 2016 Feb. doi: 10.1053/j.gastro.2016.02.032.

6. Silvernale C, et al. Racial disparity in healthcare utilization among patients with Irritable Bowel Syndrome: results from a multicenter cohort. Neurogastroenterol Motil. 2021 May. doi: 10.1111/nmo.14039.

7. Hearn M, et al. Stigma and irritable bowel syndrome: a taboo subject? Lancet Gastroenterol Hepatol. 2020 Jun. doi: 10.1016/S2468-1253(19)30348-6.

8. Yan XJ, et al. The impact of stigma on medication adherence in patients with functional dyspepsia. Neurogastroenterol Motil. 2021 Feb. doi: 10.1111/nmo.13956.

9. Twersky SE, et al. The Impact of Limited English Proficiency on Healthcare Access and Outcomes in the U.S.: A Scoping Review. Healthcare (Basel). 2024 Jan. doi: 10.3390/healthcare12030364.

10. Bayly JE, et al. Limited English proficiency and reported receipt of colorectal cancer screening among adults 45-75 in 2019 and 2021. Prev Med Rep. 2024 Feb. doi: 10.1016/j.pmedr.2024.102638.

11. Cheng K, et al. Epidemiology of Irritable Bowel Syndrome in a Large Academic Safety-Net Hospital. J Clin Med. 2024 Feb. doi: 10.3390/jcm13051314.

12. Breiding MJ, Armour BS. The association between disability and intimate partner violence in the United States. Ann Epidemiol. 2015 Jun. doi: 10.1016/j.annepidem.2015.03.017.

13. Mitra M, et al. Prevalence and characteristics of sexual violence against men with disabilities. Am J Prev Med. 2016 Mar. doi: 10.1016/j.amepre.2015.07.030.

14. Bahafzallah L, et al. Motivational Interviewing in Ethnic Populations. J Immigr Minor Health. 2020 Aug. doi: 10.1007/s10903-019-00940-3.

Introduction: Cases

Patient 1: A 57-year-old man with post-prandial distress variant functional dyspepsia (FD) was recommended to start nortriptyline. He previously established primary care with a physician he met at a barbershop health fair in Harlem, who referred him for specialty evaluation. Today, he presents for follow-up and reports he did not take this medication because he heard it is an antidepressant. How would you counsel him? 

Patient 2: A 61-year-old woman was previously diagnosed with mixed variant irritable bowel syndrome (IBS-M). Her symptoms have not significantly changed. Her prior workup has been reassuring and consistent with IBS-M. Despite this, the patient pushes to repeat a colonoscopy, fearful that something is being missed or that she is not being offered care because of her undocumented status. How do you respond? 

Patient 3: A 36-year-old man is followed for the management of generalized anxiety disorder and functional heartburn. He was started on low-dose amitriptyline with some benefit, but follow-up has been sporadic. On further discussion, he reports financial stressors, time barriers, and difficulty scheduling a meeting with his union representative for work accommodations as he lives in a more rural community. How do you reply?

Patient 4: A 74-year-old man with Parkinson’s disease who uses a wheelchair has functional constipation that is well controlled on his current regimen. He has never undergone colon cancer screening. He occasionally notices blood in his stool, so a colonoscopy was recommended to confirm that his hematochezia reflects functional constipation complicated by hemorrhoids. He is concerned about the bowel preparation required for a colonoscopy given his limited mobility, as his insurance does not cover assistance at home. He does not have family members to help him. How can you assist him?

Social determinants of health, health disparities, and DGBIs

Social determinants of health affect all aspects of patient care, with an increasing body of published work looking at potential disparities in organ-based and structural diseases.^1,2,3,4 However, little has been done to explore their influence on disorders of gut-brain interaction or DGBIs.

From a pathophysiologic perspective, the impact of biopsychosocial stressors is particularly relevant in patients with DGBIs. As DGBIs cannot be diagnosed with a single laboratory or endoscopic test, the patient history is of the utmost importance and physician-patient rapport is paramount in their treatment. Such rapport may be more difficult to establish in patients coming from historically marginalized and minoritized communities who may be distrustful of healthcare as an institution of (discriminatory) power. 

 

Potential DGBI management pitfalls in historically marginalized or minoritized communities

For racial and ethnic minorities in the United States, disparities in healthcare take on many forms. People from racial and ethnic minority communities are less likely to receive a gastroenterology consultation and those with IBS are more likely to undergo procedures as compared to White patients with IBS.⁶ Implicit bias may lead to fewer specialist referrals, and specialty care may be limited or unavailable in some areas. Patients may prefer seeing providers in their own community, with whom they share racial or ethnic identities, which could lead to fewer referrals to specialists outside of the community.

Historical discrimination contributes to a lack of trust in healthcare professionals, which may lead patients to favor more objective diagnostics such as endoscopy or view being counseled against invasive procedures as having necessary care denied. Due to a broader cultural stigma surrounding mental illness, patients may be more hesitant to utilize neuromodulators, which have historically been used for psychiatric diagnoses, as it may lead them to conflate their GI illness with mental illness.^7,8

Since DGBIs cannot be diagnosed with a single test or managed with a single treatment modality, providing excellent care for patients with DGBIs requires clear communication. For patients with limited English proficiency (LEP), access to high-quality language assistance is the foundation of comprehensive care. Interpreter use (or lack thereof) may limit the ability to obtain a complete and accurate clinical history, which can lead to fewer referrals to specialists and increased reliance on endoscopic evaluations that may not be clinically indicated.

These language barriers affect patients on many levels – in their ability to understand instructions for medication administration, preparation for procedures, and return precautions – which may ultimately lead to poorer responses to therapy or delays in care. LEP alone is broadly associated with fewer referrals for outpatient follow-up, adverse health outcomes and complications, and longer hospital stays.⁹ These disparities can be mitigated by investing in high-quality interpreter services, providing instructions and forms in multiple languages, and engaging the patient’s family and social supports according to their preferences.

People experiencing poverty (urban and rural) face challenges across multiple domains including access to healthcare, health insurance, stable housing and employment, and more. Many patients seek care at federally qualified health centers, which may face greater difficulties coordinating care with external gastroenterologists.¹⁰

 

Insurance barriers limit access to essential medications, tests, and procedures, and create delays in establishing care with specialists. Significant psychological stress and higher rates of comorbid anxiety and depression contribute to increased IBS severity.¹¹ Financial limitations may limit dietary choices, which can further exacerbate DGBI symptoms. Long work hours with limited flexibility may prohibit them from presenting for regular follow-ups and establishing advanced DGBI care such as with a dietitian or psychologist.

Patients with disabilities face many of the health inequities previously discussed, as well as additional challenges with physical accessibility, transportation, exclusion from education and employment, discrimination, and stigma. Higher prevalence of comorbid mental illness and higher rates of intimate partner violence and interpersonal violence all contribute to DGBI severity and challenges with access to care.^12,13 Patients with disabilities may struggle to arrive at appointments, maneuver through the building or exam room, and ultimately follow recommended care plans.

 

How to approach DGBIs in historically marginalized and minoritized communities

Returning to the patients from the introduction, how would you counsel each of them?

Patient 1: We can discuss with the patient how nortriptyline and other typical antidepressants can and often are used for indications other than depression. These medications modify centrally-mediated pain signaling and many patients with functional dyspepsia experience a significant benefit. It is critical to build on the rapport that was established at the community health outreach event and to explore the patient’s concerns thoroughly.

Patient 2: We would begin by inquiring about her underlying fears associated with her symptoms and seek to understand her goals for repeat intervention. We can review the risks of endoscopy and shift the focus to improving her symptoms. If we can improve her bowel habits or her pain, her desire for further interventions may lessen. 

Patient 3: It will be important to work within the realistic time and monetary constraints in this patient’s life. We can validate him and the challenges he is facing, provide positive reinforcement for the progress he has made so far, and avoid disparaging him for the aspects of the treatment plan he has been unable to follow through with. As he reported a benefit from amitriptyline, we can consider increasing his dose as a feasible next step. 

Patient 4: We can encourage the patient to discuss with his primary care physician how they may be able to coordinate an inpatient admission for colonoscopy preparation. Given his co-morbidities, this avenue will provide him dedicated support to help him adequately prep to ensure a higher quality examination and limit the need for repeat procedures.

DGBI care in historically marginalized and minoritized communities: A call to action

Understanding cultural differences and existing disparities in care is essential to improving care for patients from historically minoritized communities with DGBIs. Motivational interviewing and shared decision-making, with acknowledgment of social and cultural differences, allow us to work together with patients and their support systems to set and achieve feasible goals.¹⁴

 

To address known health disparities, offices can take steps to ensure the accessibility of language, forms, physical space, providers, and care teams. Providing culturally sensitive care and lowering barriers to care are the first steps to effecting meaningful change for patients with DGBIs from historically minoritized communities.

Dr. Yu is based at Division of Gastroenterology and Hepatology, Boston Medical Center and Boston University, both in Boston, Massachusetts. Dr. Dimino and Dr. Vélez are based at the Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, both in Boston, Massachusetts. Dr. Yu, Dr. Dimino, and Dr. Vélez do not have any conflicts of interest for this article.

Additional Online Resources

Form Accessibility 

• Intake Form Guidance for Providers
• Making Your Clinic Welcoming to LGBTQ Patients
• Transgender data collection in the electronic health record: Current concepts and issues

Language Accessibility 

• Overcoming the challenges of providing care to limited English proficient patients

Physical Accessibility 

• Access to Medical Care for Individuals with Mobility Disabilities
• Making your medical office accessible

References

1. Zavala VA, et al. Cancer health disparities in racial/ethnic minorities in the United States. Br J Cancer. 2021 Jan. doi: 10.1038/s41416-020-01038-6.

2. Kardashian A, et al. Health disparities in chronic liver disease. Hepatology. 2023 Apr. doi: 10.1002/hep.32743.

3. Nephew LD, Serper M. Racial, Gender, and Socioeconomic Disparities in Liver Transplantation. Liver Transpl. 2021 Jun. doi: 10.1002/lt.25996.

4. Anyane-Yeboa A, et al. The Impact of the Social Determinants of Health on Disparities in Inflammatory Bowel Disease. Clin Gastroenterol Hepatol. 2022 Nov. doi: 10.1016/j.cgh.2022.03.011.

5. Drossman DA. Functional Gastrointestinal Disorders: History, Pathophysiology, Clinical Features and Rome IV. Gastroenterology. 2016 Feb. doi: 10.1053/j.gastro.2016.02.032.

6. Silvernale C, et al. Racial disparity in healthcare utilization among patients with Irritable Bowel Syndrome: results from a multicenter cohort. Neurogastroenterol Motil. 2021 May. doi: 10.1111/nmo.14039.

7. Hearn M, et al. Stigma and irritable bowel syndrome: a taboo subject? Lancet Gastroenterol Hepatol. 2020 Jun. doi: 10.1016/S2468-1253(19)30348-6.

8. Yan XJ, et al. The impact of stigma on medication adherence in patients with functional dyspepsia. Neurogastroenterol Motil. 2021 Feb. doi: 10.1111/nmo.13956.

9. Twersky SE, et al. The Impact of Limited English Proficiency on Healthcare Access and Outcomes in the U.S.: A Scoping Review. Healthcare (Basel). 2024 Jan. doi: 10.3390/healthcare12030364.

10. Bayly JE, et al. Limited English proficiency and reported receipt of colorectal cancer screening among adults 45-75 in 2019 and 2021. Prev Med Rep. 2024 Feb. doi: 10.1016/j.pmedr.2024.102638.

11. Cheng K, et al. Epidemiology of Irritable Bowel Syndrome in a Large Academic Safety-Net Hospital. J Clin Med. 2024 Feb. doi: 10.3390/jcm13051314.

12. Breiding MJ, Armour BS. The association between disability and intimate partner violence in the United States. Ann Epidemiol. 2015 Jun. doi: 10.1016/j.annepidem.2015.03.017.

13. Mitra M, et al. Prevalence and characteristics of sexual violence against men with disabilities. Am J Prev Med. 2016 Mar. doi: 10.1016/j.amepre.2015.07.030.

14. Bahafzallah L, et al. Motivational Interviewing in Ethnic Populations. J Immigr Minor Health. 2020 Aug. doi: 10.1007/s10903-019-00940-3.

SAN DIEGO –A novel gene risk score, informed by machine learning, predicted weight-loss outcomes after Roux-en-Y gastric bypass (RYGB) surgery, a new analysis showed.

The findings suggested that the MyPhenome test (Phenomix Sciences) can help clinicians identify the patients most likely to benefit from bariatric procedures and at a greater risk for long-term weight regain after surgery.

“Patients with both a high genetic risk score and rare mutations in the leptin-melanocortin pathway (LMP) had significantly worse outcomes, maintaining only 4.9% total body weight loss [TBWL] over 15 years compared to up to 24.8% in other genetic groups,” Phenomix Sciences Co-founder Andres Acosta, MD, PhD, told GI & Hepatology News.

The study included details on the score’s development and predictive capability. It was presented at Digestive Disease Week^® (DDW) 2025

‘More Precise Bariatric Care’

The researchers recently developed a machine learning-assisted gene risk score for calories to satiation (CTSGRS), which mainly involves genes in the LMP. To assess the role of the score with or without LMP gene variants on weight loss and weight recurrence after RYGB, they identified 707 patients with a history of bariatric procedures from the Mayo Clinic Biobank. Patients with duodenal switch, revisional procedures, or who used antiobesity medications or became pregnant during follow-up were excluded.

To make predictions for 442 of the patients, the team first collected anthropometric data up to 15 years after RYGB. Then they used a two-step approach: Assessing for monogenic variants in the LMP and defining participants as carriers (LMP+) or noncarriers (LMP-). Then they defined the gene risk score (CTSGRS+ or CTSGRS-).

The result was four groups: LMP+/CTSGRS+, LMP+/CTSGRS-, LMP-/CTSGRS+, and LMP-/CTSGRS-. Multiple regression analysis was used to analyze TBWL percentage (TBWL%) between the groups at different timepoints, adjusting for baseline weight, age, and gender.

At the 10-year follow-up, the LMP+/CTSGRS+ group demonstrated a significantly higher weight recurrence (regain) of TBW% compared to the other groups.

At 15 years post-RYGB, the mean TBWL% for LMP+/CTSGRS+ was -4.9 vs -20.3 for LMP+/CTSGRS-, -18.0 for LMP-/CTSGRS+, and -24.8 for LMP-/CTSGRS-.

Further analyses showed that the LMP+/CTSGRS+ group had significantly less weight loss than LMP+/CTSGRS- and LMP-/CTSGRS- groups.

Based on the findings, the authors wrote, “Genotyping patients could improve the implementation of individualized weight-loss interventions, enhance weight-loss outcomes, and/or may explain one of the etiological factors associated with weight recurrence after RYGB.”

Acosta noted, “We’re actively expanding our research to include more diverse populations by age, sex, and race. This includes ongoing analysis to understand whether certain demographic or physiological characteristics affect how the test performs, particularly in the context of bariatric surgery.”

The team also is investigating the benefits of phenotyping for obesity comorbidities such as heart disease and diabetes, he said, and exploring whether early interventions in high-risk patients can prevent long-term weight regain and improve outcomes.

In addition, Acosta said, the team recently launched “the first prospective, placebo-controlled clinical trial using the MyPhenome test to predict response to semaglutide.” That study is based on earlier findings showing that patients identified with a Hungry Gut phenotype lost nearly twice as much weight on semaglutide compared with those who tested negative.

Overall, he concluded, “These findings open the door to more precise bariatric care. When we understand a patient’s biological drivers of obesity, we can make better decisions about the right procedure, follow-up, and long-term support. This moves us away from a one-size-fits-all model to care rooted in each patient’s unique biology.”

 

Potentially Paradigm-Shifting

Onur Kutlu, MD, associate professor of surgery and director of the Metabolic Surgery and Metabolic Health Program at the Miller School of Medicine, University of Miami, in Miami, Florida, commented on the study for GI & Hepatology News. “By integrating polygenic risk scores into predictive models, the authors offer an innovative method for identifying patients at elevated risk for weight regain following RYGB.”

“Their findings support the hypothesis that genetic predisposition — particularly involving energy homeostasis pathways — may underlie differential postoperative trajectories,” he said. “This approach has the potential to shift the paradigm from reactive to proactive management of weight recurrence.”

Because current options for treat weight regain are “suboptimal,” he said, “prevention becomes paramount. Preoperative identification of high-risk individuals could inform surgical decision-making, enable earlier interventions, and facilitate personalized postoperative monitoring and support.”

“If validated in larger, prospective cohorts, genetic risk stratification could enhance the precision of bariatric care and improve long-term outcomes,” he added. “Future studies should aim to validate these genetic models across diverse populations and explore how integration of behavioral, psychological, and genetic data may further refine patient selection and care pathways.”

The study was funded by Mayo Clinic and Phenomix Sciences. Gila Therapeutics and Phenomix Sciences licensed Acosta’s research technologies from the University of Florida and Mayo Clinic. Acosta declared receiving consultant fees in the past 5 years from Rhythm Pharmaceuticals, Gila Therapeutics, Amgen, General Mills, BI, Currax, Nestle, Phenomix Sciences, Bausch Health, and RareDiseases, as well as funding support from the National Institutes of Health, Vivus Pharmaceuticals, Novo Nordisk, Apollo Endosurgery, Satiogen Pharmaceuticals, Spatz Medical, and Rhythm Pharmaceuticals. Kutlu declared having no conflicts of interest.

A version of this article appeared on Medscape.com.

SAN DIEGO –A novel gene risk score, informed by machine learning, predicted weight-loss outcomes after Roux-en-Y gastric bypass (RYGB) surgery, a new analysis showed.

The findings suggested that the MyPhenome test (Phenomix Sciences) can help clinicians identify the patients most likely to benefit from bariatric procedures and at a greater risk for long-term weight regain after surgery.

“Patients with both a high genetic risk score and rare mutations in the leptin-melanocortin pathway (LMP) had significantly worse outcomes, maintaining only 4.9% total body weight loss [TBWL] over 15 years compared to up to 24.8% in other genetic groups,” Phenomix Sciences Co-founder Andres Acosta, MD, PhD, told GI & Hepatology News.

The study included details on the score’s development and predictive capability. It was presented at Digestive Disease Week^® (DDW) 2025

‘More Precise Bariatric Care’

The researchers recently developed a machine learning-assisted gene risk score for calories to satiation (CTSGRS), which mainly involves genes in the LMP. To assess the role of the score with or without LMP gene variants on weight loss and weight recurrence after RYGB, they identified 707 patients with a history of bariatric procedures from the Mayo Clinic Biobank. Patients with duodenal switch, revisional procedures, or who used antiobesity medications or became pregnant during follow-up were excluded.

To make predictions for 442 of the patients, the team first collected anthropometric data up to 15 years after RYGB. Then they used a two-step approach: Assessing for monogenic variants in the LMP and defining participants as carriers (LMP+) or noncarriers (LMP-). Then they defined the gene risk score (CTSGRS+ or CTSGRS-).

The result was four groups: LMP+/CTSGRS+, LMP+/CTSGRS-, LMP-/CTSGRS+, and LMP-/CTSGRS-. Multiple regression analysis was used to analyze TBWL percentage (TBWL%) between the groups at different timepoints, adjusting for baseline weight, age, and gender.

At the 10-year follow-up, the LMP+/CTSGRS+ group demonstrated a significantly higher weight recurrence (regain) of TBW% compared to the other groups.

At 15 years post-RYGB, the mean TBWL% for LMP+/CTSGRS+ was -4.9 vs -20.3 for LMP+/CTSGRS-, -18.0 for LMP-/CTSGRS+, and -24.8 for LMP-/CTSGRS-.

Further analyses showed that the LMP+/CTSGRS+ group had significantly less weight loss than LMP+/CTSGRS- and LMP-/CTSGRS- groups.

Based on the findings, the authors wrote, “Genotyping patients could improve the implementation of individualized weight-loss interventions, enhance weight-loss outcomes, and/or may explain one of the etiological factors associated with weight recurrence after RYGB.”

Acosta noted, “We’re actively expanding our research to include more diverse populations by age, sex, and race. This includes ongoing analysis to understand whether certain demographic or physiological characteristics affect how the test performs, particularly in the context of bariatric surgery.”

The team also is investigating the benefits of phenotyping for obesity comorbidities such as heart disease and diabetes, he said, and exploring whether early interventions in high-risk patients can prevent long-term weight regain and improve outcomes.

In addition, Acosta said, the team recently launched “the first prospective, placebo-controlled clinical trial using the MyPhenome test to predict response to semaglutide.” That study is based on earlier findings showing that patients identified with a Hungry Gut phenotype lost nearly twice as much weight on semaglutide compared with those who tested negative.

Overall, he concluded, “These findings open the door to more precise bariatric care. When we understand a patient’s biological drivers of obesity, we can make better decisions about the right procedure, follow-up, and long-term support. This moves us away from a one-size-fits-all model to care rooted in each patient’s unique biology.”

 

Potentially Paradigm-Shifting

Onur Kutlu, MD, associate professor of surgery and director of the Metabolic Surgery and Metabolic Health Program at the Miller School of Medicine, University of Miami, in Miami, Florida, commented on the study for GI & Hepatology News. “By integrating polygenic risk scores into predictive models, the authors offer an innovative method for identifying patients at elevated risk for weight regain following RYGB.”

“Their findings support the hypothesis that genetic predisposition — particularly involving energy homeostasis pathways — may underlie differential postoperative trajectories,” he said. “This approach has the potential to shift the paradigm from reactive to proactive management of weight recurrence.”

Because current options for treat weight regain are “suboptimal,” he said, “prevention becomes paramount. Preoperative identification of high-risk individuals could inform surgical decision-making, enable earlier interventions, and facilitate personalized postoperative monitoring and support.”

“If validated in larger, prospective cohorts, genetic risk stratification could enhance the precision of bariatric care and improve long-term outcomes,” he added. “Future studies should aim to validate these genetic models across diverse populations and explore how integration of behavioral, psychological, and genetic data may further refine patient selection and care pathways.”

The study was funded by Mayo Clinic and Phenomix Sciences. Gila Therapeutics and Phenomix Sciences licensed Acosta’s research technologies from the University of Florida and Mayo Clinic. Acosta declared receiving consultant fees in the past 5 years from Rhythm Pharmaceuticals, Gila Therapeutics, Amgen, General Mills, BI, Currax, Nestle, Phenomix Sciences, Bausch Health, and RareDiseases, as well as funding support from the National Institutes of Health, Vivus Pharmaceuticals, Novo Nordisk, Apollo Endosurgery, Satiogen Pharmaceuticals, Spatz Medical, and Rhythm Pharmaceuticals. Kutlu declared having no conflicts of interest.

A version of this article appeared on Medscape.com.

SAN DIEGO –A novel gene risk score, informed by machine learning, predicted weight-loss outcomes after Roux-en-Y gastric bypass (RYGB) surgery, a new analysis showed.

The findings suggested that the MyPhenome test (Phenomix Sciences) can help clinicians identify the patients most likely to benefit from bariatric procedures and at a greater risk for long-term weight regain after surgery.

“Patients with both a high genetic risk score and rare mutations in the leptin-melanocortin pathway (LMP) had significantly worse outcomes, maintaining only 4.9% total body weight loss [TBWL] over 15 years compared to up to 24.8% in other genetic groups,” Phenomix Sciences Co-founder Andres Acosta, MD, PhD, told GI & Hepatology News.

The study included details on the score’s development and predictive capability. It was presented at Digestive Disease Week^® (DDW) 2025

‘More Precise Bariatric Care’

The researchers recently developed a machine learning-assisted gene risk score for calories to satiation (CTSGRS), which mainly involves genes in the LMP. To assess the role of the score with or without LMP gene variants on weight loss and weight recurrence after RYGB, they identified 707 patients with a history of bariatric procedures from the Mayo Clinic Biobank. Patients with duodenal switch, revisional procedures, or who used antiobesity medications or became pregnant during follow-up were excluded.

To make predictions for 442 of the patients, the team first collected anthropometric data up to 15 years after RYGB. Then they used a two-step approach: Assessing for monogenic variants in the LMP and defining participants as carriers (LMP+) or noncarriers (LMP-). Then they defined the gene risk score (CTSGRS+ or CTSGRS-).

The result was four groups: LMP+/CTSGRS+, LMP+/CTSGRS-, LMP-/CTSGRS+, and LMP-/CTSGRS-. Multiple regression analysis was used to analyze TBWL percentage (TBWL%) between the groups at different timepoints, adjusting for baseline weight, age, and gender.

At the 10-year follow-up, the LMP+/CTSGRS+ group demonstrated a significantly higher weight recurrence (regain) of TBW% compared to the other groups.

At 15 years post-RYGB, the mean TBWL% for LMP+/CTSGRS+ was -4.9 vs -20.3 for LMP+/CTSGRS-, -18.0 for LMP-/CTSGRS+, and -24.8 for LMP-/CTSGRS-.

Further analyses showed that the LMP+/CTSGRS+ group had significantly less weight loss than LMP+/CTSGRS- and LMP-/CTSGRS- groups.

Based on the findings, the authors wrote, “Genotyping patients could improve the implementation of individualized weight-loss interventions, enhance weight-loss outcomes, and/or may explain one of the etiological factors associated with weight recurrence after RYGB.”

Acosta noted, “We’re actively expanding our research to include more diverse populations by age, sex, and race. This includes ongoing analysis to understand whether certain demographic or physiological characteristics affect how the test performs, particularly in the context of bariatric surgery.”

The team also is investigating the benefits of phenotyping for obesity comorbidities such as heart disease and diabetes, he said, and exploring whether early interventions in high-risk patients can prevent long-term weight regain and improve outcomes.

In addition, Acosta said, the team recently launched “the first prospective, placebo-controlled clinical trial using the MyPhenome test to predict response to semaglutide.” That study is based on earlier findings showing that patients identified with a Hungry Gut phenotype lost nearly twice as much weight on semaglutide compared with those who tested negative.

Overall, he concluded, “These findings open the door to more precise bariatric care. When we understand a patient’s biological drivers of obesity, we can make better decisions about the right procedure, follow-up, and long-term support. This moves us away from a one-size-fits-all model to care rooted in each patient’s unique biology.”

 

Potentially Paradigm-Shifting

Onur Kutlu, MD, associate professor of surgery and director of the Metabolic Surgery and Metabolic Health Program at the Miller School of Medicine, University of Miami, in Miami, Florida, commented on the study for GI & Hepatology News. “By integrating polygenic risk scores into predictive models, the authors offer an innovative method for identifying patients at elevated risk for weight regain following RYGB.”

“Their findings support the hypothesis that genetic predisposition — particularly involving energy homeostasis pathways — may underlie differential postoperative trajectories,” he said. “This approach has the potential to shift the paradigm from reactive to proactive management of weight recurrence.”

Because current options for treat weight regain are “suboptimal,” he said, “prevention becomes paramount. Preoperative identification of high-risk individuals could inform surgical decision-making, enable earlier interventions, and facilitate personalized postoperative monitoring and support.”

“If validated in larger, prospective cohorts, genetic risk stratification could enhance the precision of bariatric care and improve long-term outcomes,” he added. “Future studies should aim to validate these genetic models across diverse populations and explore how integration of behavioral, psychological, and genetic data may further refine patient selection and care pathways.”

The study was funded by Mayo Clinic and Phenomix Sciences. Gila Therapeutics and Phenomix Sciences licensed Acosta’s research technologies from the University of Florida and Mayo Clinic. Acosta declared receiving consultant fees in the past 5 years from Rhythm Pharmaceuticals, Gila Therapeutics, Amgen, General Mills, BI, Currax, Nestle, Phenomix Sciences, Bausch Health, and RareDiseases, as well as funding support from the National Institutes of Health, Vivus Pharmaceuticals, Novo Nordisk, Apollo Endosurgery, Satiogen Pharmaceuticals, Spatz Medical, and Rhythm Pharmaceuticals. Kutlu declared having no conflicts of interest.

A version of this article appeared on Medscape.com.

Research on cannabis use disorder (CUD) has mainly focused on individuals aged < 65 years, but a recently published study in JAMA Network Open found one-third of older veterans who had used cannabis in the previous 30 days screened positive for CUD.

The cross-sectional study of 4503 veterans aged 65 to 84 years from the US Department of Veterans Affairs (VA) Cannabis and Aging Cohort found 57% of participants reported lifetime cannabis use, with 29% citing medical reasons, usually for pain management. About 10% reported using cannabis in the previous 30 days, with 52% reporting use for ≥ 20 days in a month. The odds of CUD were higher among men, respondents aged < 76 years, individuals with anxiety, and individuals who reported any illicit drug use or frequent cannabis use.

In 2019, 9.8% of veterans reported using cannabis in the previous year. In 2019 to 2020, > 20% of veterans aged 18 to 44 years said they had used cannabis in the previous 6 months. According to VA Health Systems Research, about 1 in 11 veterans had used cannabis in the previous year. Compared to the general US population, recent cannabis use was similar or slightly lower among veterans. Among those with previous year use, however, the percentage of veterans using cannabis for medical purposes was more than double that of the general population.

Older veterans are particularly at risk for CUD. Cannabis use can increase the chance of neuropsychiatric disorders, respiratory symptoms, and cardiovascular outcomes—all leading causes of death in older adults. They also have an elevated risk of suicidal ideation and therefore may be particularly susceptible to adverse effects of cannabis, even if used for therapeutic purposes.

In addition to CUD, older veterans may be at risk for tetrahydrocannabinol (THC) intoxication if they are unable to tolerate cannabis potency or the latent THC components found in products marketed as only having cannabidiol. THC is the primary psychoactive compound found in the cannabis plant and interacts with brain cannabinoid receptors to affect mood, perception, and various bodily functions. Cannabis potency has increased from about 3% in the 1980s to about 15% in recent years; the average THC-to-CBD ratio has increased substantially over the past decade.

Unlike veterans aged 18 to 25 years, those aged ≥ 65 years are less likely to use recreational cannabis, are more likely to use medicinal cannabis recommended by a health care professional, and report use for pain management, insomnia, and mental health (including posttraumatic stress disorder [PTSD]). Some research indicates that rates of cannabis use and CUD are particularly elevated among veterans with PTSD and major depressive disorder who may use cannabis as a means of coping with negative affect and sleep disturbances. PTSD is recognized as a qualifying condition by states that have legalized medicinal cannabis. 

Sleep disturbance, especially in conjunction with PTSD, is associated with CUD among veterans. According to the VA, research does not support cannabis as an effective PTSD treatment, a reason the 2023 VA/DoD Clinical Practice Guideline for PTSD does not recommend it for that use. In 2020, lifetime prevalence of CUD among veterans was 9.2%; the prevalence of past-6-month CUD diagnoses among veterans was 2.7%. Among veterans with PTSD, however, CUD rates were much higher (12.1%).

Current VA guidelines recommend that patients with CUD be offered referral to mental health services for evidence-based treatments, including motivational interviews, contingency management, and cognitive behavioral therapy. The JAMA Network Open study notes the importance of screening and informing older veterans about the risks of cannabis use: “Unidentified, patients cannot be offered existing evidence-based treatments. Despite increasing cannabis use among older adults, there is an inadequate evidence base on therapeutic benefits and potential harms from cannabis use among older people.”

Research on cannabis use disorder (CUD) has mainly focused on individuals aged < 65 years, but a recently published study in JAMA Network Open found one-third of older veterans who had used cannabis in the previous 30 days screened positive for CUD.

The cross-sectional study of 4503 veterans aged 65 to 84 years from the US Department of Veterans Affairs (VA) Cannabis and Aging Cohort found 57% of participants reported lifetime cannabis use, with 29% citing medical reasons, usually for pain management. About 10% reported using cannabis in the previous 30 days, with 52% reporting use for ≥ 20 days in a month. The odds of CUD were higher among men, respondents aged < 76 years, individuals with anxiety, and individuals who reported any illicit drug use or frequent cannabis use.

In 2019, 9.8% of veterans reported using cannabis in the previous year. In 2019 to 2020, > 20% of veterans aged 18 to 44 years said they had used cannabis in the previous 6 months. According to VA Health Systems Research, about 1 in 11 veterans had used cannabis in the previous year. Compared to the general US population, recent cannabis use was similar or slightly lower among veterans. Among those with previous year use, however, the percentage of veterans using cannabis for medical purposes was more than double that of the general population.

Older veterans are particularly at risk for CUD. Cannabis use can increase the chance of neuropsychiatric disorders, respiratory symptoms, and cardiovascular outcomes—all leading causes of death in older adults. They also have an elevated risk of suicidal ideation and therefore may be particularly susceptible to adverse effects of cannabis, even if used for therapeutic purposes.

In addition to CUD, older veterans may be at risk for tetrahydrocannabinol (THC) intoxication if they are unable to tolerate cannabis potency or the latent THC components found in products marketed as only having cannabidiol. THC is the primary psychoactive compound found in the cannabis plant and interacts with brain cannabinoid receptors to affect mood, perception, and various bodily functions. Cannabis potency has increased from about 3% in the 1980s to about 15% in recent years; the average THC-to-CBD ratio has increased substantially over the past decade.

Unlike veterans aged 18 to 25 years, those aged ≥ 65 years are less likely to use recreational cannabis, are more likely to use medicinal cannabis recommended by a health care professional, and report use for pain management, insomnia, and mental health (including posttraumatic stress disorder [PTSD]). Some research indicates that rates of cannabis use and CUD are particularly elevated among veterans with PTSD and major depressive disorder who may use cannabis as a means of coping with negative affect and sleep disturbances. PTSD is recognized as a qualifying condition by states that have legalized medicinal cannabis. 

Sleep disturbance, especially in conjunction with PTSD, is associated with CUD among veterans. According to the VA, research does not support cannabis as an effective PTSD treatment, a reason the 2023 VA/DoD Clinical Practice Guideline for PTSD does not recommend it for that use. In 2020, lifetime prevalence of CUD among veterans was 9.2%; the prevalence of past-6-month CUD diagnoses among veterans was 2.7%. Among veterans with PTSD, however, CUD rates were much higher (12.1%).

Current VA guidelines recommend that patients with CUD be offered referral to mental health services for evidence-based treatments, including motivational interviews, contingency management, and cognitive behavioral therapy. The JAMA Network Open study notes the importance of screening and informing older veterans about the risks of cannabis use: “Unidentified, patients cannot be offered existing evidence-based treatments. Despite increasing cannabis use among older adults, there is an inadequate evidence base on therapeutic benefits and potential harms from cannabis use among older people.”

Research on cannabis use disorder (CUD) has mainly focused on individuals aged < 65 years, but a recently published study in JAMA Network Open found one-third of older veterans who had used cannabis in the previous 30 days screened positive for CUD.

The cross-sectional study of 4503 veterans aged 65 to 84 years from the US Department of Veterans Affairs (VA) Cannabis and Aging Cohort found 57% of participants reported lifetime cannabis use, with 29% citing medical reasons, usually for pain management. About 10% reported using cannabis in the previous 30 days, with 52% reporting use for ≥ 20 days in a month. The odds of CUD were higher among men, respondents aged < 76 years, individuals with anxiety, and individuals who reported any illicit drug use or frequent cannabis use.

In 2019, 9.8% of veterans reported using cannabis in the previous year. In 2019 to 2020, > 20% of veterans aged 18 to 44 years said they had used cannabis in the previous 6 months. According to VA Health Systems Research, about 1 in 11 veterans had used cannabis in the previous year. Compared to the general US population, recent cannabis use was similar or slightly lower among veterans. Among those with previous year use, however, the percentage of veterans using cannabis for medical purposes was more than double that of the general population.

Older veterans are particularly at risk for CUD. Cannabis use can increase the chance of neuropsychiatric disorders, respiratory symptoms, and cardiovascular outcomes—all leading causes of death in older adults. They also have an elevated risk of suicidal ideation and therefore may be particularly susceptible to adverse effects of cannabis, even if used for therapeutic purposes.

In addition to CUD, older veterans may be at risk for tetrahydrocannabinol (THC) intoxication if they are unable to tolerate cannabis potency or the latent THC components found in products marketed as only having cannabidiol. THC is the primary psychoactive compound found in the cannabis plant and interacts with brain cannabinoid receptors to affect mood, perception, and various bodily functions. Cannabis potency has increased from about 3% in the 1980s to about 15% in recent years; the average THC-to-CBD ratio has increased substantially over the past decade.

Unlike veterans aged 18 to 25 years, those aged ≥ 65 years are less likely to use recreational cannabis, are more likely to use medicinal cannabis recommended by a health care professional, and report use for pain management, insomnia, and mental health (including posttraumatic stress disorder [PTSD]). Some research indicates that rates of cannabis use and CUD are particularly elevated among veterans with PTSD and major depressive disorder who may use cannabis as a means of coping with negative affect and sleep disturbances. PTSD is recognized as a qualifying condition by states that have legalized medicinal cannabis. 

Sleep disturbance, especially in conjunction with PTSD, is associated with CUD among veterans. According to the VA, research does not support cannabis as an effective PTSD treatment, a reason the 2023 VA/DoD Clinical Practice Guideline for PTSD does not recommend it for that use. In 2020, lifetime prevalence of CUD among veterans was 9.2%; the prevalence of past-6-month CUD diagnoses among veterans was 2.7%. Among veterans with PTSD, however, CUD rates were much higher (12.1%).

Current VA guidelines recommend that patients with CUD be offered referral to mental health services for evidence-based treatments, including motivational interviews, contingency management, and cognitive behavioral therapy. The JAMA Network Open study notes the importance of screening and informing older veterans about the risks of cannabis use: “Unidentified, patients cannot be offered existing evidence-based treatments. Despite increasing cannabis use among older adults, there is an inadequate evidence base on therapeutic benefits and potential harms from cannabis use among older people.”

A new combination modality demonstrated excellent sensitivity and negative predictive value compared with endoscopy in a prospective study of at-risk veterans screened for Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC), a small comparative study in US veterans found.

BE is up to three times more prevalent in veterans than in the general population.

This and other minimally invasive approaches may reduce patient anxiety and increase screening rates, according to investigators led by Katarina B. Greer, MD, MS, of the VA Northeast Ohio Healthcare System and Case Western University in Cleveland. Such screening platforms are expected to open a window on improved prognosis for EAC by offering well-tolerated, office-based testing, the authors wrote in The American Journal of Gastroenterology.

Greer and colleagues compared standard upper endoscopy with EsoCheck (EC), a nonendoscopic esophageal balloon cell-sampling device coupled with EsoGuard (EG), a DNA-based precancer screening assay, with standard upper endoscopy, an FDA-approved minimally invasive alternative.

Sensitivity and specificity of combined EC/EG for esophagogastroduodenoscopy (EGD)-detected BE/EAC were 92.9% (95% CI, 66.1-99.8) and 72.2% (95% CI, 62.1-80.8), respectively. Positive and negative predictive values were 32.5% (95% CI, 18.6-49.1) and 98.6% (95% CI, 92.4-100), respectively.

“With its strong negative predictive power, this screening modality could be a first-line tool available to a greater number of patients,” Greer and associates wrote. “Data from this test support the notion that EC could be performed as a triaging test to increase the yield of diagnostic upper endoscopy 2.5-fold.”

The US rates of EAC have increased more than six-fold in the past four decades and continue to rise. In 2023, 21,560 cases of EAC were diagnosed here. The prognosis for EAC is still poor, with fewer than 22% of patients surviving beyond 5 years.

Current guidelines recommend sedated EGD for patients with chronic gastroesophageal reflux disease (GERD) and additional BE risk factors such as smoking, obesity, and family history. This strategy, however, often fails to detect BE when symptoms are well controlled with over-the-counter or physician-prescribed therapies, Greer and colleagues noted. It also fails to detect BE in individuals without GERD, who comprise 40% of those who develop EAC.

Fewer than 5% of EACs are diagnosed as early-stage lesions caught by surveillance of patients with previously detected BE.

 

Study Details

The researchers recruited veterans meeting American College of Gastroenterology criteria for endoscopic BE and EAC screening at the Louis Stokes Cleveland Veterans Affairs Medical Center.

Of 782 eligible veterans, 130 (16.6%) entered the study and 124 completed screening. Common reasons for nonparticipation included completion of upper endoscopy outside of the VA healthcare system, lack of interest in joining a research study, and no recommendation for screening from referring gastroenterology or primary care providers. Eligible candidates had gastroesophageal reflux disorder plus three additional risk factors, such as smoking, higher BMI, male sex, age 50 years or older, and family history. The mean number of risk factors was 4.1.

“Available data suggest that family history is the strongest predictor of BE diagnosis, as prevalence of BE among those with family history was 23%,” Greer’s group wrote. “This points to high priority of pursuing screening in patients with family history of the condition, followed by patients who share multiple risk factors.”

All participants completed unsedated EC-guided distal esophageal sampling followed by a sedated EGD on the same day. The prevalence of BE/EAC was 12.9% (n = 14/2), based on standard EGD.

“The study was not powered to prospectively determine EC diagnostic accuracy for subgroups of nondysplastic and dysplastic BE and EAC. These data are reported for this device in development studies but not available for our study population,” the authors wrote. In comparison, they noted, the Cytosponge-TFF3, another nonendoscopic screening device for EAC and BE, exhibited lower sensitivity of 79.5%-87.2%, depending on lesion length, but higher specificity of 92.4%.

 

Procedural Anxiety

Baseline scores on the short-form six-item Spielberger State-Trait Anxiety Inventory-6 (STAI-6) revealed notable levels of periprocedural anxiety. STAI-6 scores range from 20 to 80, with higher scores indicating more severe anxiety. In the VA study, scores ranged from 20 to 60, and most domains constituting the scores were the same before and after the procedure. Participants did, however, report a statistically significant decrease in sense of worry after EC and reported good tolerability for both EC and EG.

Offering an outsider’s perspective on the study, Joshua Sloan, DO, an esophageal gastroenterologist at University of Minnesota Medical Center in Minneapolis, said that with the acceleration of US rates of EAC, developing a nonendoscopic screening tool to improve identification of Barrett’s and perhaps early EAC is important. “The study by Greer et al helps support the use of nonendoscopic screening with EsoCheck and EsoGuard to identify these conditions,” he told GI & Hepatology News. “It will be interesting to see similar studies in the non-VA population as well. As the study notes, veterans are an enriched population with a higher prevalence of Barrett’s esophagus.”

Ultimately, Sloan added, “the hope is to increase our ability to identify and manage BE before it becomes EAC. Nonendoscopic screening tools have the potential to increase diagnosis and funnel the appropriate patients for endoscopic surveillance.”

 

The Bottom Line 

“Calculations regarding effectiveness of the two-step screening strategy afforded by EC indicate that the burden of screening would be reduced by at least half (53%),” the authors wrote. Since the estimated size of the US screen-eligible population ranges from 19.7 million to 120.1 million, noninvasive tools could significantly decrease EGD procedures. A formal cost effectiveness analysis is being conducted and will be published separately.

This study was funded by a Department of Defense award.

Co-Author Chak reported device patents assigned to Case Western Reserve University and licensed to Lucid Diagnostics. The other authors had no competing interests to declare. Sloan disclosed speaking and/or advisory work for Sanofi-Regeneron, Phathom Pharmaceuticals, and Takeda Pharmaceuticals unrelated to his comments.

A version of this article appeared on Medscape.com.

A new combination modality demonstrated excellent sensitivity and negative predictive value compared with endoscopy in a prospective study of at-risk veterans screened for Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC), a small comparative study in US veterans found.

BE is up to three times more prevalent in veterans than in the general population.

This and other minimally invasive approaches may reduce patient anxiety and increase screening rates, according to investigators led by Katarina B. Greer, MD, MS, of the VA Northeast Ohio Healthcare System and Case Western University in Cleveland. Such screening platforms are expected to open a window on improved prognosis for EAC by offering well-tolerated, office-based testing, the authors wrote in The American Journal of Gastroenterology.

Greer and colleagues compared standard upper endoscopy with EsoCheck (EC), a nonendoscopic esophageal balloon cell-sampling device coupled with EsoGuard (EG), a DNA-based precancer screening assay, with standard upper endoscopy, an FDA-approved minimally invasive alternative.

Sensitivity and specificity of combined EC/EG for esophagogastroduodenoscopy (EGD)-detected BE/EAC were 92.9% (95% CI, 66.1-99.8) and 72.2% (95% CI, 62.1-80.8), respectively. Positive and negative predictive values were 32.5% (95% CI, 18.6-49.1) and 98.6% (95% CI, 92.4-100), respectively.

“With its strong negative predictive power, this screening modality could be a first-line tool available to a greater number of patients,” Greer and associates wrote. “Data from this test support the notion that EC could be performed as a triaging test to increase the yield of diagnostic upper endoscopy 2.5-fold.”

The US rates of EAC have increased more than six-fold in the past four decades and continue to rise. In 2023, 21,560 cases of EAC were diagnosed here. The prognosis for EAC is still poor, with fewer than 22% of patients surviving beyond 5 years.

Current guidelines recommend sedated EGD for patients with chronic gastroesophageal reflux disease (GERD) and additional BE risk factors such as smoking, obesity, and family history. This strategy, however, often fails to detect BE when symptoms are well controlled with over-the-counter or physician-prescribed therapies, Greer and colleagues noted. It also fails to detect BE in individuals without GERD, who comprise 40% of those who develop EAC.

Fewer than 5% of EACs are diagnosed as early-stage lesions caught by surveillance of patients with previously detected BE.

 

Study Details

The researchers recruited veterans meeting American College of Gastroenterology criteria for endoscopic BE and EAC screening at the Louis Stokes Cleveland Veterans Affairs Medical Center.

Of 782 eligible veterans, 130 (16.6%) entered the study and 124 completed screening. Common reasons for nonparticipation included completion of upper endoscopy outside of the VA healthcare system, lack of interest in joining a research study, and no recommendation for screening from referring gastroenterology or primary care providers. Eligible candidates had gastroesophageal reflux disorder plus three additional risk factors, such as smoking, higher BMI, male sex, age 50 years or older, and family history. The mean number of risk factors was 4.1.

“Available data suggest that family history is the strongest predictor of BE diagnosis, as prevalence of BE among those with family history was 23%,” Greer’s group wrote. “This points to high priority of pursuing screening in patients with family history of the condition, followed by patients who share multiple risk factors.”

All participants completed unsedated EC-guided distal esophageal sampling followed by a sedated EGD on the same day. The prevalence of BE/EAC was 12.9% (n = 14/2), based on standard EGD.

“The study was not powered to prospectively determine EC diagnostic accuracy for subgroups of nondysplastic and dysplastic BE and EAC. These data are reported for this device in development studies but not available for our study population,” the authors wrote. In comparison, they noted, the Cytosponge-TFF3, another nonendoscopic screening device for EAC and BE, exhibited lower sensitivity of 79.5%-87.2%, depending on lesion length, but higher specificity of 92.4%.

 

Procedural Anxiety

Baseline scores on the short-form six-item Spielberger State-Trait Anxiety Inventory-6 (STAI-6) revealed notable levels of periprocedural anxiety. STAI-6 scores range from 20 to 80, with higher scores indicating more severe anxiety. In the VA study, scores ranged from 20 to 60, and most domains constituting the scores were the same before and after the procedure. Participants did, however, report a statistically significant decrease in sense of worry after EC and reported good tolerability for both EC and EG.

Offering an outsider’s perspective on the study, Joshua Sloan, DO, an esophageal gastroenterologist at University of Minnesota Medical Center in Minneapolis, said that with the acceleration of US rates of EAC, developing a nonendoscopic screening tool to improve identification of Barrett’s and perhaps early EAC is important. “The study by Greer et al helps support the use of nonendoscopic screening with EsoCheck and EsoGuard to identify these conditions,” he told GI & Hepatology News. “It will be interesting to see similar studies in the non-VA population as well. As the study notes, veterans are an enriched population with a higher prevalence of Barrett’s esophagus.”

Ultimately, Sloan added, “the hope is to increase our ability to identify and manage BE before it becomes EAC. Nonendoscopic screening tools have the potential to increase diagnosis and funnel the appropriate patients for endoscopic surveillance.”

 

The Bottom Line 

“Calculations regarding effectiveness of the two-step screening strategy afforded by EC indicate that the burden of screening would be reduced by at least half (53%),” the authors wrote. Since the estimated size of the US screen-eligible population ranges from 19.7 million to 120.1 million, noninvasive tools could significantly decrease EGD procedures. A formal cost effectiveness analysis is being conducted and will be published separately.

This study was funded by a Department of Defense award.

Co-Author Chak reported device patents assigned to Case Western Reserve University and licensed to Lucid Diagnostics. The other authors had no competing interests to declare. Sloan disclosed speaking and/or advisory work for Sanofi-Regeneron, Phathom Pharmaceuticals, and Takeda Pharmaceuticals unrelated to his comments.

A version of this article appeared on Medscape.com.

A new combination modality demonstrated excellent sensitivity and negative predictive value compared with endoscopy in a prospective study of at-risk veterans screened for Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC), a small comparative study in US veterans found.

BE is up to three times more prevalent in veterans than in the general population.

This and other minimally invasive approaches may reduce patient anxiety and increase screening rates, according to investigators led by Katarina B. Greer, MD, MS, of the VA Northeast Ohio Healthcare System and Case Western University in Cleveland. Such screening platforms are expected to open a window on improved prognosis for EAC by offering well-tolerated, office-based testing, the authors wrote in The American Journal of Gastroenterology.

Greer and colleagues compared standard upper endoscopy with EsoCheck (EC), a nonendoscopic esophageal balloon cell-sampling device coupled with EsoGuard (EG), a DNA-based precancer screening assay, with standard upper endoscopy, an FDA-approved minimally invasive alternative.

Sensitivity and specificity of combined EC/EG for esophagogastroduodenoscopy (EGD)-detected BE/EAC were 92.9% (95% CI, 66.1-99.8) and 72.2% (95% CI, 62.1-80.8), respectively. Positive and negative predictive values were 32.5% (95% CI, 18.6-49.1) and 98.6% (95% CI, 92.4-100), respectively.

“With its strong negative predictive power, this screening modality could be a first-line tool available to a greater number of patients,” Greer and associates wrote. “Data from this test support the notion that EC could be performed as a triaging test to increase the yield of diagnostic upper endoscopy 2.5-fold.”

The US rates of EAC have increased more than six-fold in the past four decades and continue to rise. In 2023, 21,560 cases of EAC were diagnosed here. The prognosis for EAC is still poor, with fewer than 22% of patients surviving beyond 5 years.

Current guidelines recommend sedated EGD for patients with chronic gastroesophageal reflux disease (GERD) and additional BE risk factors such as smoking, obesity, and family history. This strategy, however, often fails to detect BE when symptoms are well controlled with over-the-counter or physician-prescribed therapies, Greer and colleagues noted. It also fails to detect BE in individuals without GERD, who comprise 40% of those who develop EAC.

Fewer than 5% of EACs are diagnosed as early-stage lesions caught by surveillance of patients with previously detected BE.

 

Study Details

The researchers recruited veterans meeting American College of Gastroenterology criteria for endoscopic BE and EAC screening at the Louis Stokes Cleveland Veterans Affairs Medical Center.

Of 782 eligible veterans, 130 (16.6%) entered the study and 124 completed screening. Common reasons for nonparticipation included completion of upper endoscopy outside of the VA healthcare system, lack of interest in joining a research study, and no recommendation for screening from referring gastroenterology or primary care providers. Eligible candidates had gastroesophageal reflux disorder plus three additional risk factors, such as smoking, higher BMI, male sex, age 50 years or older, and family history. The mean number of risk factors was 4.1.

“Available data suggest that family history is the strongest predictor of BE diagnosis, as prevalence of BE among those with family history was 23%,” Greer’s group wrote. “This points to high priority of pursuing screening in patients with family history of the condition, followed by patients who share multiple risk factors.”

All participants completed unsedated EC-guided distal esophageal sampling followed by a sedated EGD on the same day. The prevalence of BE/EAC was 12.9% (n = 14/2), based on standard EGD.

“The study was not powered to prospectively determine EC diagnostic accuracy for subgroups of nondysplastic and dysplastic BE and EAC. These data are reported for this device in development studies but not available for our study population,” the authors wrote. In comparison, they noted, the Cytosponge-TFF3, another nonendoscopic screening device for EAC and BE, exhibited lower sensitivity of 79.5%-87.2%, depending on lesion length, but higher specificity of 92.4%.

 

Procedural Anxiety

Baseline scores on the short-form six-item Spielberger State-Trait Anxiety Inventory-6 (STAI-6) revealed notable levels of periprocedural anxiety. STAI-6 scores range from 20 to 80, with higher scores indicating more severe anxiety. In the VA study, scores ranged from 20 to 60, and most domains constituting the scores were the same before and after the procedure. Participants did, however, report a statistically significant decrease in sense of worry after EC and reported good tolerability for both EC and EG.

Offering an outsider’s perspective on the study, Joshua Sloan, DO, an esophageal gastroenterologist at University of Minnesota Medical Center in Minneapolis, said that with the acceleration of US rates of EAC, developing a nonendoscopic screening tool to improve identification of Barrett’s and perhaps early EAC is important. “The study by Greer et al helps support the use of nonendoscopic screening with EsoCheck and EsoGuard to identify these conditions,” he told GI & Hepatology News. “It will be interesting to see similar studies in the non-VA population as well. As the study notes, veterans are an enriched population with a higher prevalence of Barrett’s esophagus.”

Ultimately, Sloan added, “the hope is to increase our ability to identify and manage BE before it becomes EAC. Nonendoscopic screening tools have the potential to increase diagnosis and funnel the appropriate patients for endoscopic surveillance.”

 

The Bottom Line 

“Calculations regarding effectiveness of the two-step screening strategy afforded by EC indicate that the burden of screening would be reduced by at least half (53%),” the authors wrote. Since the estimated size of the US screen-eligible population ranges from 19.7 million to 120.1 million, noninvasive tools could significantly decrease EGD procedures. A formal cost effectiveness analysis is being conducted and will be published separately.

This study was funded by a Department of Defense award.

Co-Author Chak reported device patents assigned to Case Western Reserve University and licensed to Lucid Diagnostics. The other authors had no competing interests to declare. Sloan disclosed speaking and/or advisory work for Sanofi-Regeneron, Phathom Pharmaceuticals, and Takeda Pharmaceuticals unrelated to his comments.

A version of this article appeared on Medscape.com.

Walnut consumption modified the fecal microbiota and metabolome, improved insulin response, and reduced gut permeability in adults with obesity, a small study showed.

“Less than 10% of adults are meeting their fiber needs each day, and walnuts are a source of dietary fiber, which helps nourish the gut microbiota,” study coauthor Hannah Holscher, PhD, RD, associate professor of nutrition at the University of Illinois at Urbana-Champaign, told GI & Hepatology News.

Holscher and her colleagues previously conducted a study on the effects of walnut consumption on the human intestinal microbiota “and found interesting results,” she said. Among 18 healthy men and women with a mean age of 53 years, “walnuts enriched intestinal microorganisms, including Roseburia that provide important gut-health promoting attributes, like short-chain fatty acid production. We also saw lower proinflammatory secondary bile acid concentrations in individuals that ate walnuts.”

The current study, presented at NUTRITION 2025 in Orlando, Florida, found similar benefits among 30 adults with obesity but without diabetes or gastrointestinal disease.

 

Walnut Halves, Walnut Oil, Corn Oil — Compared

The researchers aimed to determine the impact of walnut consumption on the gut microbiome, serum and fecal bile acid profiles, systemic inflammation, and oral glucose tolerance to a mixed-meal challenge.

Participants were enrolled in a randomized, controlled, crossover, complete feeding trial with three 3-week conditions, each identical except for walnut halves (WH), walnut oil (WO), or corn oil (CO) in the diet. A 3-week washout separated each condition.

“This was a fully controlled dietary feeding intervention,” Holscher said. “We provided their breakfast, lunch, snacks and dinners — all of their foods and beverages during the three dietary intervention periods that lasted for 3 weeks each. Their base diet consisted of typical American foods that you would find in a grocery store in central Illinois.”

Fecal samples were collected on days 18-20. On day 20, participants underwent a 6-hour mixed-meal tolerance test (75 g glucose + treatment) with a fasting blood draw followed by blood sampling every 30 minutes.

The fecal microbiome and microbiota were assessed using metagenomic and amplicon sequencing, respectively. Fecal microbial metabolites were quantified using gas chromatography-mass spectrometry.

Blood glucose, insulin, and inflammatory biomarkers (interleukin-6, tumor necrosis factor-alpha, C-reactive protein, and lipopolysaccharide-binding protein) were quantified. Fecal and circulating bile acids were measured via liquid chromatography tandem mass spectrometry.

Gut permeability was assessed by quantifying 24-hour urinary excretion of orally ingested sucralose and erythritol on day 21.

Linear mixed-effects models and repeated measures ANOVA were used for the statistical analysis.

The team found that Roseburia spp were greatest following WH (3.9%) vs WO (1.6) and CO (1.9); Lachnospiraceae UCG-001 and UCG-004 were also greatest with WH vs WO and CO.

WH fecal isobutyrate concentrations (5.41 µmol/g) were lower than WO (7.17 µmol/g) and CO (7.77). Similarly, fecal isovalerate concentrations were lowest with WH (7.84 µmol/g) vs WO (10.3µmol/g) and CO (11.6 µmol/g).

In contrast, indoles were highest in WH (36.8 µmol/g) vs WO (6.78 µmol/g) and CO (8.67µmol/g).

No differences in glucose concentrations were seen among groups. The 2-hour area under the curve (AUC) for insulin was lower with WH (469 µIU/mL/min) and WO (494) vs CO (604 µIU/mL/min).

The 4-hour AUC for glycolithocholic acid was lower with WH vs WO and CO. Furthermore, sucralose recovery was lowest following WH (10.5) vs WO (14.3) and CO (14.6).

“Our current efforts are focused on understanding connections between plasma bile acids and glycemic control (ie, blood glucose and insulin concentrations),” Holscher said. “We are also interested in studying individualized or personalized responses, since people had different magnitudes of responses.”

In addition, she said, “as the gut microbiome is one of the factors that can underpin the physiological response to the diet, we are interested in determining if there are microbial signatures that are predictive of glycemic control.”

Because the research is still in the early stages, at this point, Holscher simply encourages people to eat a variety of fruits, vegetables, whole grains, legumes and nuts to meet their daily fiber recommendations and support their gut microbiome.

This study was funded by a USDA NIFA grant. No competing interests were reported.

A version of this article appeared on Medscape.com . 

Walnut consumption modified the fecal microbiota and metabolome, improved insulin response, and reduced gut permeability in adults with obesity, a small study showed.

“Less than 10% of adults are meeting their fiber needs each day, and walnuts are a source of dietary fiber, which helps nourish the gut microbiota,” study coauthor Hannah Holscher, PhD, RD, associate professor of nutrition at the University of Illinois at Urbana-Champaign, told GI & Hepatology News.

Holscher and her colleagues previously conducted a study on the effects of walnut consumption on the human intestinal microbiota “and found interesting results,” she said. Among 18 healthy men and women with a mean age of 53 years, “walnuts enriched intestinal microorganisms, including Roseburia that provide important gut-health promoting attributes, like short-chain fatty acid production. We also saw lower proinflammatory secondary bile acid concentrations in individuals that ate walnuts.”

The current study, presented at NUTRITION 2025 in Orlando, Florida, found similar benefits among 30 adults with obesity but without diabetes or gastrointestinal disease.

 

Walnut Halves, Walnut Oil, Corn Oil — Compared

The researchers aimed to determine the impact of walnut consumption on the gut microbiome, serum and fecal bile acid profiles, systemic inflammation, and oral glucose tolerance to a mixed-meal challenge.

Participants were enrolled in a randomized, controlled, crossover, complete feeding trial with three 3-week conditions, each identical except for walnut halves (WH), walnut oil (WO), or corn oil (CO) in the diet. A 3-week washout separated each condition.

“This was a fully controlled dietary feeding intervention,” Holscher said. “We provided their breakfast, lunch, snacks and dinners — all of their foods and beverages during the three dietary intervention periods that lasted for 3 weeks each. Their base diet consisted of typical American foods that you would find in a grocery store in central Illinois.”

Fecal samples were collected on days 18-20. On day 20, participants underwent a 6-hour mixed-meal tolerance test (75 g glucose + treatment) with a fasting blood draw followed by blood sampling every 30 minutes.

The fecal microbiome and microbiota were assessed using metagenomic and amplicon sequencing, respectively. Fecal microbial metabolites were quantified using gas chromatography-mass spectrometry.

Blood glucose, insulin, and inflammatory biomarkers (interleukin-6, tumor necrosis factor-alpha, C-reactive protein, and lipopolysaccharide-binding protein) were quantified. Fecal and circulating bile acids were measured via liquid chromatography tandem mass spectrometry.

Gut permeability was assessed by quantifying 24-hour urinary excretion of orally ingested sucralose and erythritol on day 21.

Linear mixed-effects models and repeated measures ANOVA were used for the statistical analysis.

The team found that Roseburia spp were greatest following WH (3.9%) vs WO (1.6) and CO (1.9); Lachnospiraceae UCG-001 and UCG-004 were also greatest with WH vs WO and CO.

WH fecal isobutyrate concentrations (5.41 µmol/g) were lower than WO (7.17 µmol/g) and CO (7.77). Similarly, fecal isovalerate concentrations were lowest with WH (7.84 µmol/g) vs WO (10.3µmol/g) and CO (11.6 µmol/g).

In contrast, indoles were highest in WH (36.8 µmol/g) vs WO (6.78 µmol/g) and CO (8.67µmol/g).

No differences in glucose concentrations were seen among groups. The 2-hour area under the curve (AUC) for insulin was lower with WH (469 µIU/mL/min) and WO (494) vs CO (604 µIU/mL/min).

The 4-hour AUC for glycolithocholic acid was lower with WH vs WO and CO. Furthermore, sucralose recovery was lowest following WH (10.5) vs WO (14.3) and CO (14.6).

“Our current efforts are focused on understanding connections between plasma bile acids and glycemic control (ie, blood glucose and insulin concentrations),” Holscher said. “We are also interested in studying individualized or personalized responses, since people had different magnitudes of responses.”

In addition, she said, “as the gut microbiome is one of the factors that can underpin the physiological response to the diet, we are interested in determining if there are microbial signatures that are predictive of glycemic control.”

Because the research is still in the early stages, at this point, Holscher simply encourages people to eat a variety of fruits, vegetables, whole grains, legumes and nuts to meet their daily fiber recommendations and support their gut microbiome.

This study was funded by a USDA NIFA grant. No competing interests were reported.

A version of this article appeared on Medscape.com . 

Walnut consumption modified the fecal microbiota and metabolome, improved insulin response, and reduced gut permeability in adults with obesity, a small study showed.

“Less than 10% of adults are meeting their fiber needs each day, and walnuts are a source of dietary fiber, which helps nourish the gut microbiota,” study coauthor Hannah Holscher, PhD, RD, associate professor of nutrition at the University of Illinois at Urbana-Champaign, told GI & Hepatology News.

Holscher and her colleagues previously conducted a study on the effects of walnut consumption on the human intestinal microbiota “and found interesting results,” she said. Among 18 healthy men and women with a mean age of 53 years, “walnuts enriched intestinal microorganisms, including Roseburia that provide important gut-health promoting attributes, like short-chain fatty acid production. We also saw lower proinflammatory secondary bile acid concentrations in individuals that ate walnuts.”

The current study, presented at NUTRITION 2025 in Orlando, Florida, found similar benefits among 30 adults with obesity but without diabetes or gastrointestinal disease.

 

Walnut Halves, Walnut Oil, Corn Oil — Compared

The researchers aimed to determine the impact of walnut consumption on the gut microbiome, serum and fecal bile acid profiles, systemic inflammation, and oral glucose tolerance to a mixed-meal challenge.

Participants were enrolled in a randomized, controlled, crossover, complete feeding trial with three 3-week conditions, each identical except for walnut halves (WH), walnut oil (WO), or corn oil (CO) in the diet. A 3-week washout separated each condition.

“This was a fully controlled dietary feeding intervention,” Holscher said. “We provided their breakfast, lunch, snacks and dinners — all of their foods and beverages during the three dietary intervention periods that lasted for 3 weeks each. Their base diet consisted of typical American foods that you would find in a grocery store in central Illinois.”

Fecal samples were collected on days 18-20. On day 20, participants underwent a 6-hour mixed-meal tolerance test (75 g glucose + treatment) with a fasting blood draw followed by blood sampling every 30 minutes.

The fecal microbiome and microbiota were assessed using metagenomic and amplicon sequencing, respectively. Fecal microbial metabolites were quantified using gas chromatography-mass spectrometry.

Blood glucose, insulin, and inflammatory biomarkers (interleukin-6, tumor necrosis factor-alpha, C-reactive protein, and lipopolysaccharide-binding protein) were quantified. Fecal and circulating bile acids were measured via liquid chromatography tandem mass spectrometry.

Gut permeability was assessed by quantifying 24-hour urinary excretion of orally ingested sucralose and erythritol on day 21.

Linear mixed-effects models and repeated measures ANOVA were used for the statistical analysis.

The team found that Roseburia spp were greatest following WH (3.9%) vs WO (1.6) and CO (1.9); Lachnospiraceae UCG-001 and UCG-004 were also greatest with WH vs WO and CO.

WH fecal isobutyrate concentrations (5.41 µmol/g) were lower than WO (7.17 µmol/g) and CO (7.77). Similarly, fecal isovalerate concentrations were lowest with WH (7.84 µmol/g) vs WO (10.3µmol/g) and CO (11.6 µmol/g).

In contrast, indoles were highest in WH (36.8 µmol/g) vs WO (6.78 µmol/g) and CO (8.67µmol/g).

No differences in glucose concentrations were seen among groups. The 2-hour area under the curve (AUC) for insulin was lower with WH (469 µIU/mL/min) and WO (494) vs CO (604 µIU/mL/min).

The 4-hour AUC for glycolithocholic acid was lower with WH vs WO and CO. Furthermore, sucralose recovery was lowest following WH (10.5) vs WO (14.3) and CO (14.6).

“Our current efforts are focused on understanding connections between plasma bile acids and glycemic control (ie, blood glucose and insulin concentrations),” Holscher said. “We are also interested in studying individualized or personalized responses, since people had different magnitudes of responses.”

In addition, she said, “as the gut microbiome is one of the factors that can underpin the physiological response to the diet, we are interested in determining if there are microbial signatures that are predictive of glycemic control.”

Because the research is still in the early stages, at this point, Holscher simply encourages people to eat a variety of fruits, vegetables, whole grains, legumes and nuts to meet their daily fiber recommendations and support their gut microbiome.

This study was funded by a USDA NIFA grant. No competing interests were reported.

A version of this article appeared on Medscape.com .