Gastroenterology. 2021 Jun 16;S0016-5085(21)03138-3. doi: 10.1053/j.gastro.2021.06.024.Online ahead of print.

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

Author information

• ¹Division of Gastroenterology and Hepatology, Department of Internal Medicine 3, Medical University of Vienna, Vienna, Austria.
• ²Division of Gastroenterology and Hepatology, Department of Internal Medicine 3, Medical University of Vienna, Vienna, Austria; Centre for Microbiology and Environmental Systems Science, Department of Microbiology and Ecosystem Science, Division of Microbial Ecology, University of Vienna, Vienna, Austria.
• ³Centre for Microbiology and Environmental Systems Science, Department of Microbiology and Ecosystem Science, Division of Microbial Ecology, University of Vienna, Vienna, Austria.
• ⁴Joint Microbiome Facility of the Medical University of Vienna and the University of Vienna, Vienna, Austria; Division of Microbiology, Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
• ⁵Centre for Microbiology and Environmental Systems Science, Department of Microbiology and Ecosystem Science, Division of Microbial Ecology, University of Vienna, Vienna, Austria; Joint Microbiome Facility of the Medical University of Vienna and the University of Vienna, Vienna, Austria.
• ⁶Department of Cranio-Maxillofacial and Oral Surgery, Medical University of Vienna, Vienna, Austria.
• ⁷Department of Pathology, Medical University of Vienna, Vienna, Austria.
• ⁸Center for Public Health, Department of Epidemiology, Medical University of Vienna, Vienna, Austria.
• ⁹Vienna Biocenter Core Facilities (VBCF), Vienna, Austria.
• ¹⁰CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
• ¹¹Ludwig Demling Endoscopy Center of Excellence, Division of Gastroenterology, Friedrich-Alexander-University, Erlangen, Germany.
• ¹²Faculty of Chemistry, Institute of Biological Chemistry, University of Vienna, Vienna, Austria; Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
• ¹³Division of Gastroenterology and Hepatology, Department of Internal Medicine 3, Medical University of Vienna, Vienna, Austria. Electronic address: christoph.gasche@meduniwien.ac.at.

Abstract

Background & aims: Irritable bowel syndrome (IBS) and inflammatory bowel diseases result in a substantial reduction in quality of life and a considerable socio-economic impact. In IBS, diagnosis and treatment options are limited, but evidence for an 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 1,426 patients at two European university-based endoscopy centers. One-hundred-seventeen patients were selected for in-depth molecular and microscopic analysis using 16S-rRNA 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 IBS and 34% of ulcerative colitis (UC) patients, compared to 6% of controls (p<0.001). These yellow-green adherent layers of the ileum and right-sided colon were microscopically confirmed to be dense bacterial biofilms. 16S-sequencing link 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 UC with disrupted bile acid metabolism and bacterial dysbiosis. They provide novel insight into the pathophysiology of IBS and UC, illustrating that biofilm can be seen as a tipping point in the development of dysbiosis and disease.