Mucosal Biofilms Are an Endoscopic Feature of Irritable Bowel Syndrome and Ulcerative Colitis

Irritable bowel syndrome (IBS) and inflammatory bowel diseases result in a substantial reduction in quality of life and a considerable socioeconomic impact. In IBS, diagnosis and treatment options are limited, but evidence for involvement of the gut microbiome in disease pathophysiology is emerging....

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Veröffentlicht in:Gastroenterology (New York, N.Y. 1943) N.Y. 1943), 2021-10, Vol.161 (4), p.1245-1256.e20
Hauptverfasser: Baumgartner, Maximilian, Lang, Michaela, Holley, Hunter, Crepaz, Daniel, Hausmann, Bela, Pjevac, Petra, Moser, Doris, Haller, Felix, Hof, Fabian, Beer, Andrea, Orgler, Elisabeth, Frick, Adrian, Khare, Vineeta, Evstatiev, Rayko, Strohmaier, Susanne, Primas, Christian, Dolak, Werner, Köcher, Thomas, Klavins, Kristaps, Rath, Timo, Neurath, Markus F., Berry, David, Makristathis, Athanasios, Muttenthaler, Markus, Gasche, Christoph
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container_end_page 1256.e20
container_issue 4
container_start_page 1245
container_title Gastroenterology (New York, N.Y. 1943)
container_volume 161
creator Baumgartner, Maximilian
Lang, Michaela
Holley, Hunter
Crepaz, Daniel
Hausmann, Bela
Pjevac, Petra
Moser, Doris
Haller, Felix
Hof, Fabian
Beer, Andrea
Orgler, Elisabeth
Frick, Adrian
Khare, Vineeta
Evstatiev, Rayko
Strohmaier, Susanne
Primas, Christian
Dolak, Werner
Köcher, Thomas
Klavins, Kristaps
Rath, Timo
Neurath, Markus F.
Berry, David
Makristathis, Athanasios
Muttenthaler, Markus
Gasche, Christoph
description Irritable bowel syndrome (IBS) and inflammatory bowel diseases result in a substantial reduction in quality of life and a considerable socioeconomic impact. In IBS, diagnosis and treatment options are limited, but evidence for involvement of the gut microbiome in disease pathophysiology is emerging. Here we analyzed the prevalence of endoscopically visible mucosal biofilms in gastrointestinal disease and associated changes in microbiome composition and metabolism. The presence of mucosal biofilms was assessed in 1426 patients at 2 European university-based endoscopy centers. One-hundred and seventeen patients were selected for in-depth molecular and microscopic analysis using 16S ribosomal RNA gene amplicon-sequencing of colonic biopsies and fecal samples, confocal microscopy with deep learning–based image analysis, scanning electron microscopy, metabolomics, and in vitro biofilm formation assays. Biofilms were present in 57% of patients with IBS and 34% of patients with ulcerative colitis compared with 6% of controls (P < .001). These yellow-green adherent layers of the ileum and right-sided colon were microscopically confirmed to be dense bacterial biofilms. 16S-sequencing links the presence of biofilms to a dysbiotic gut microbiome, including overgrowth of Escherichia coli and Ruminococcus gnavus. R. gnavus isolates cultivated from patient biofilms also formed biofilms in vitro. Metabolomic analysis found an accumulation of bile acids within biofilms that correlated with fecal bile acid excretion, linking this phenotype with a mechanism of diarrhea. The presence of mucosal biofilms is an endoscopic feature in a subgroup of IBS and ulcerative colitis with disrupted bile acid metabolism and bacterial dysbiosis. They provide novel insight into the pathophysiology of IBS and ulcerative colitis, illustrating that biofilm can be seen as a tipping point in the development of dysbiosis and disease. [Display omitted] Bacterial biofilms were observed by colonoscopy as yellow-green membranous layers on the mucosa of the small and large intestinal junction and are specifically prevalent in irritable bowel syndrome and inflammatory bowel disease.
doi_str_mv 10.1053/j.gastro.2021.06.024
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In IBS, diagnosis and treatment options are limited, but evidence for involvement of the gut microbiome in disease pathophysiology is emerging. Here we analyzed the prevalence of endoscopically visible mucosal biofilms in gastrointestinal disease and associated changes in microbiome composition and metabolism. The presence of mucosal biofilms was assessed in 1426 patients at 2 European university-based endoscopy centers. One-hundred and seventeen patients were selected for in-depth molecular and microscopic analysis using 16S ribosomal RNA gene amplicon-sequencing of colonic biopsies and fecal samples, confocal microscopy with deep learning–based image analysis, scanning electron microscopy, metabolomics, and in vitro biofilm formation assays. Biofilms were present in 57% of patients with IBS and 34% of patients with ulcerative colitis compared with 6% of controls (P &lt; .001). These yellow-green adherent layers of the ileum and right-sided colon were microscopically confirmed to be dense bacterial biofilms. 16S-sequencing links the presence of biofilms to a dysbiotic gut microbiome, including overgrowth of Escherichia coli and Ruminococcus gnavus. R. gnavus isolates cultivated from patient biofilms also formed biofilms in vitro. Metabolomic analysis found an accumulation of bile acids within biofilms that correlated with fecal bile acid excretion, linking this phenotype with a mechanism of diarrhea. The presence of mucosal biofilms is an endoscopic feature in a subgroup of IBS and ulcerative colitis with disrupted bile acid metabolism and bacterial dysbiosis. They provide novel insight into the pathophysiology of IBS and ulcerative colitis, illustrating that biofilm can be seen as a tipping point in the development of dysbiosis and disease. 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These yellow-green adherent layers of the ileum and right-sided colon were microscopically confirmed to be dense bacterial biofilms. 16S-sequencing links the presence of biofilms to a dysbiotic gut microbiome, including overgrowth of Escherichia coli and Ruminococcus gnavus. R. gnavus isolates cultivated from patient biofilms also formed biofilms in vitro. Metabolomic analysis found an accumulation of bile acids within biofilms that correlated with fecal bile acid excretion, linking this phenotype with a mechanism of diarrhea. The presence of mucosal biofilms is an endoscopic feature in a subgroup of IBS and ulcerative colitis with disrupted bile acid metabolism and bacterial dysbiosis. They provide novel insight into the pathophysiology of IBS and ulcerative colitis, illustrating that biofilm can be seen as a tipping point in the development of dysbiosis and disease. 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ispartof Gastroenterology (New York, N.Y. 1943), 2021-10, Vol.161 (4), p.1245-1256.e20
issn 0016-5085
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source MEDLINE; Elsevier ScienceDirect Journals; Alma/SFX Local Collection
subjects Austria
Bacteria - growth & development
Bacteria - metabolism
Bacteria - ultrastructure
Bacterial–Epithelial Interaction
Biofilms - growth & development
Case-Control Studies
Colitis, Ulcerative - metabolism
Colitis, Ulcerative - microbiology
Colitis, Ulcerative - pathology
Colon - metabolism
Colon - microbiology
Colon - pathology
Colonoscopy
Deep Learning
Endoscopy
Functional Gastrointestinal Disorders
Gastrointestinal Microbiome
Germany
Humans
Image Interpretation, Computer-Assisted
Intestinal Mucosa - metabolism
Intestinal Mucosa - microbiology
Intestinal Mucosa - pathology
Irritable Bowel Syndrome - metabolism
Irritable Bowel Syndrome - microbiology
Irritable Bowel Syndrome - pathology
Metabolomics
Microbiota
Microscopy, Confocal
Microscopy, Electron, Scanning
Original Research
Predictive Value of Tests
Ribotyping
title Mucosal Biofilms Are an Endoscopic Feature of Irritable Bowel Syndrome and Ulcerative Colitis
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