Fungi and bacteria cooperate to form inflammatory gut biofilms

Fungi and bacteria in the gastrointestinal tract collaboratively form biofilms that may exacerbate inflammation in patients with inflammatory bowel disease (IBD), a review article concluded.

In particular, the investigators found patients with Crohn’s disease (CD) had higher levels of the fungus Candida tropicalis, and of two bacteria, Escherichia coli and Serratia marcescens, compared with healthy family members.

Furthermore, these three organisms “worked together to form robust biofilms capable of exacerbating intestinal inflammation,” wrote authors Christopher L. Hager, MD, and Mahmoud A. Ghannoum, PhD, of the center for medical mycology at Case Western Reserve University, Cleveland, and University Hospitals Cleveland Medical Center.

This “interkingdom interaction” suggests a potential role for antifungals combined with probiotics as a treatment strategy for patients with IBD, they said in their review article discussing both their own studies to date and those by other research groups.

“These studies clearly demonstrate that mycobiome/bacteriome interactions play an important role in the perpetuation of GI inflammation,” they wrote (Dig Liver Dis. 2017 Nov;49[11]:1171-6). “Not only have we shown that fungi are important for overall GI tract health, we have also shown that overgrowth of the fungus due to imbalance has deleterious effects on the gastric mucosa.”

Dr. Ghannoum and his colleagues first highlighted the importance of the mycobiome in a 2010 study that used deep sequencing to characterize the human oral fungal community (PLOS Pathogens. 2010 Jan 8. doi: 10.1371/journal.ppat.1000713). They found that humans were colonized with Candida, as was expected, but also with species including Aspergillus, Cryptococcus, and Fusarium, which was unexpected, Dr. Hager and Dr. Ghannoum wrote in their review.

In their more recent work, Dr. Ghannoum, Dr. Hager, and their coinvestigators compared CD patients with their healthy relatives and found increased levels of E. coli, S. marcescens, and the fungus C. tropicalis in the gastrointestinal tract (mBio. 2016 Sep 20. doi: 10.1128/mBio.01250-16). In vitro, those three organisms cooperate to form biofilms that could activate the host immune response, they said.

“These findings suggest a possible role of these pathogenic organisms in the initiation and perpetuation of chronic intestinal inflammation, such as that observed in patients with inflammatory bowel disease,” they wrote. “Not only has this opened up the possibility of new therapeutic approaches in patients with IBD (i.e., antifungals/antibiotics), it has also paved the way for groundbreaking research on probiotic development aimed at disrupting GI biofilm formation, thus ending a vicious cycle of chronic intestinal inflammation.”

Developing new probiotic therapies that leverage mycobiome-level observations could help overcome some limitations of current treatment options for IBD, such as biologic therapies and antibiotics, the authors wrote.

Biologics can block immune pathways implicated in mucosal inflammation and lead to potentially deleterious secondary infections, they explained. Likewise, antibiotics can be effective in controlling inflammatory symptoms but raise the concern of potentially increasing antibiotic resistance.

Although new probiotic research could provide a new avenue of treatment, development of clinical studies could be limited in part, they said, because probiotics are considered to be food supplements rather than drugs regulated by the Food and Drug Administration.

“Conducting such trials is challenging due to the lack of funding, leaving companies with very little impetus to perform long, expensive, placebo-controlled studies,” the authors wrote.

The authors declared no conflicts of interest.

Fungi and bacteria in the gastrointestinal tract collaboratively form biofilms that may exacerbate inflammation in patients with inflammatory bowel disease (IBD), a review article concluded.

In particular, the investigators found patients with Crohn’s disease (CD) had higher levels of the fungus Candida tropicalis, and of two bacteria, Escherichia coli and Serratia marcescens, compared with healthy family members.

Furthermore, these three organisms “worked together to form robust biofilms capable of exacerbating intestinal inflammation,” wrote authors Christopher L. Hager, MD, and Mahmoud A. Ghannoum, PhD, of the center for medical mycology at Case Western Reserve University, Cleveland, and University Hospitals Cleveland Medical Center.

This “interkingdom interaction” suggests a potential role for antifungals combined with probiotics as a treatment strategy for patients with IBD, they said in their review article discussing both their own studies to date and those by other research groups.

“These studies clearly demonstrate that mycobiome/bacteriome interactions play an important role in the perpetuation of GI inflammation,” they wrote (Dig Liver Dis. 2017 Nov;49[11]:1171-6). “Not only have we shown that fungi are important for overall GI tract health, we have also shown that overgrowth of the fungus due to imbalance has deleterious effects on the gastric mucosa.”

Dr. Ghannoum and his colleagues first highlighted the importance of the mycobiome in a 2010 study that used deep sequencing to characterize the human oral fungal community (PLOS Pathogens. 2010 Jan 8. doi: 10.1371/journal.ppat.1000713). They found that humans were colonized with Candida, as was expected, but also with species including Aspergillus, Cryptococcus, and Fusarium, which was unexpected, Dr. Hager and Dr. Ghannoum wrote in their review.

In their more recent work, Dr. Ghannoum, Dr. Hager, and their coinvestigators compared CD patients with their healthy relatives and found increased levels of E. coli, S. marcescens, and the fungus C. tropicalis in the gastrointestinal tract (mBio. 2016 Sep 20. doi: 10.1128/mBio.01250-16). In vitro, those three organisms cooperate to form biofilms that could activate the host immune response, they said.

“These findings suggest a possible role of these pathogenic organisms in the initiation and perpetuation of chronic intestinal inflammation, such as that observed in patients with inflammatory bowel disease,” they wrote. “Not only has this opened up the possibility of new therapeutic approaches in patients with IBD (i.e., antifungals/antibiotics), it has also paved the way for groundbreaking research on probiotic development aimed at disrupting GI biofilm formation, thus ending a vicious cycle of chronic intestinal inflammation.”

Developing new probiotic therapies that leverage mycobiome-level observations could help overcome some limitations of current treatment options for IBD, such as biologic therapies and antibiotics, the authors wrote.

Biologics can block immune pathways implicated in mucosal inflammation and lead to potentially deleterious secondary infections, they explained. Likewise, antibiotics can be effective in controlling inflammatory symptoms but raise the concern of potentially increasing antibiotic resistance.

Although new probiotic research could provide a new avenue of treatment, development of clinical studies could be limited in part, they said, because probiotics are considered to be food supplements rather than drugs regulated by the Food and Drug Administration.

“Conducting such trials is challenging due to the lack of funding, leaving companies with very little impetus to perform long, expensive, placebo-controlled studies,” the authors wrote.

The authors declared no conflicts of interest.

Fungi and bacteria in the gastrointestinal tract collaboratively form biofilms that may exacerbate inflammation in patients with inflammatory bowel disease (IBD), a review article concluded.

In particular, the investigators found patients with Crohn’s disease (CD) had higher levels of the fungus Candida tropicalis, and of two bacteria, Escherichia coli and Serratia marcescens, compared with healthy family members.

Furthermore, these three organisms “worked together to form robust biofilms capable of exacerbating intestinal inflammation,” wrote authors Christopher L. Hager, MD, and Mahmoud A. Ghannoum, PhD, of the center for medical mycology at Case Western Reserve University, Cleveland, and University Hospitals Cleveland Medical Center.

This “interkingdom interaction” suggests a potential role for antifungals combined with probiotics as a treatment strategy for patients with IBD, they said in their review article discussing both their own studies to date and those by other research groups.

“These studies clearly demonstrate that mycobiome/bacteriome interactions play an important role in the perpetuation of GI inflammation,” they wrote (Dig Liver Dis. 2017 Nov;49[11]:1171-6). “Not only have we shown that fungi are important for overall GI tract health, we have also shown that overgrowth of the fungus due to imbalance has deleterious effects on the gastric mucosa.”

Dr. Ghannoum and his colleagues first highlighted the importance of the mycobiome in a 2010 study that used deep sequencing to characterize the human oral fungal community (PLOS Pathogens. 2010 Jan 8. doi: 10.1371/journal.ppat.1000713). They found that humans were colonized with Candida, as was expected, but also with species including Aspergillus, Cryptococcus, and Fusarium, which was unexpected, Dr. Hager and Dr. Ghannoum wrote in their review.

In their more recent work, Dr. Ghannoum, Dr. Hager, and their coinvestigators compared CD patients with their healthy relatives and found increased levels of E. coli, S. marcescens, and the fungus C. tropicalis in the gastrointestinal tract (mBio. 2016 Sep 20. doi: 10.1128/mBio.01250-16). In vitro, those three organisms cooperate to form biofilms that could activate the host immune response, they said.

“These findings suggest a possible role of these pathogenic organisms in the initiation and perpetuation of chronic intestinal inflammation, such as that observed in patients with inflammatory bowel disease,” they wrote. “Not only has this opened up the possibility of new therapeutic approaches in patients with IBD (i.e., antifungals/antibiotics), it has also paved the way for groundbreaking research on probiotic development aimed at disrupting GI biofilm formation, thus ending a vicious cycle of chronic intestinal inflammation.”

Developing new probiotic therapies that leverage mycobiome-level observations could help overcome some limitations of current treatment options for IBD, such as biologic therapies and antibiotics, the authors wrote.

Biologics can block immune pathways implicated in mucosal inflammation and lead to potentially deleterious secondary infections, they explained. Likewise, antibiotics can be effective in controlling inflammatory symptoms but raise the concern of potentially increasing antibiotic resistance.

Although new probiotic research could provide a new avenue of treatment, development of clinical studies could be limited in part, they said, because probiotics are considered to be food supplements rather than drugs regulated by the Food and Drug Administration.

“Conducting such trials is challenging due to the lack of funding, leaving companies with very little impetus to perform long, expensive, placebo-controlled studies,” the authors wrote.

The authors declared no conflicts of interest.