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

Maximilian Baumgartner,1 Michaela Lang,1,2 Hunter Holley,1,2 Daniel Crepaz,2 Bela Hausmann,3,4 Petra Pjevac,2,3 Doris Moser,5 Felix Haller,1 Fabian Hof,1 Andrea Beer,6 Elisabeth Orgler,1 Adrian Frick,1 Vineeta Khare,1 Rayko Evstatiev,1 Susanne Strohmaier,7 Christian Primas,1 Werner Dolak,1 Thomas Köcher,8 Kristaps Klavins,9 Timo Rath,10Markus F. Neurath,10 David Berry,2,3 Athanasios Makristathis,3,4 Markus Muttenthaler,11,12 and Christoph Gasche1,13

BACKGROUND & AIMS: 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.

METHODS: 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.
RESULTS: 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.

CONCLUSIONS: 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.
Keywords: Endoscopy; Microbiota; Functional Gastrointestinal Disorders; Bacterial–Epithelial Interaction.