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Certain germline mutations within the DNA mismatch repair system are associated with Lynch syndrome tumors including right\u2010sided colorectal cancer with mucinous phenotype and presence of an inflammatory infiltrate. Such tumors are more often associated with bacterial biofilms, which may contribute to disease onset and progression. Inflammatory bowel diseases are also associated with colorectal cancer and intestinal dysbiosis. Herein we addressed the question, whether inflammation can aggravate colorectal cancer development under mismatch repair deficiency. MSH2<jats:sup>loxP\/loxP Vill\u2010cre<\/jats:sup> mice were crossed into the IL\u201010<jats:sup>\u2212\/\u2212<\/jats:sup> background to study the importance of inflammation and mucosal bacteria as a driver of tumorigenesis in a Lynch syndrome mouse model. An increase in large bowel tumorigenesis was found in double knockout mice both under conventional housing and under specific pathogen\u2010free conditions. This increase was mostly due to the development of proximal tumors, a hotspot for tumorigenesis in Lynch syndrome, and was associated with a higher degree of inflammation. Additionally, bacterial invasion into the mucus of tumor crypts was observed in the proximal tumors. Inflammation shifted fecal and mucosal microbiota composition and was associated with enrichment in <jats:italic>Escherichia\u2010Shigella<\/jats:italic> as well as <jats:italic>Akkermansia<\/jats:italic>, <jats:italic>Bacteroides<\/jats:italic> and <jats:italic>Parabacteroides<\/jats:italic> genera in fecal samples. Tumor\u2010bearing double knockout mice showed a similar enrichment for <jats:italic>Escherichia\u2010Shigella<\/jats:italic> and <jats:italic>Parabacteroides<\/jats:italic>. <jats:italic>Lactobacilli<\/jats:italic>, <jats:italic>Lachnospiraceae<\/jats:italic> and <jats:italic>Muribaculaceae<\/jats:italic> family members were depleted upon inflammation. In summary, chronic inflammation aggravates colonic tumorigenesis under mismatch repair deficiency and is associated with a shift in microbiota composition.<\/jats:p>","DOI":"10.1002\/ijc.33028","type":"journal-article","created":{"date-parts":[[2020,4,30]],"date-time":"2020-04-30T05:45:23Z","timestamp":1588225523000},"page":"2316-2326","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Crypt residing bacteria and proximal colonic carcinogenesis in a mouse model of Lynch syndrome"],"prefix":"10.1002","volume":"147","author":[{"given":"Michaela","family":"Lang","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine 3 Medical University of Vienna  Vienna Austria"},{"name":"Centre for Microbiology and Environmental Systems Science, Department of Microbiology and Ecosystem Science, Division of Microbial Ecology University of Vienna  Vienna 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Systems Science, Department of Microbiology and Ecosystem Science, Division of Microbial Ecology University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Jarek","sequence":"additional","affiliation":[{"name":"Genome Analytics, Helmholtz Centre for Infection Research  Braunschweig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Berry","sequence":"additional","affiliation":[{"name":"Centre for Microbiology and Environmental Systems Science, Department of Microbiology and Ecosystem Science, Division of Microbial Ecology University of Vienna  Vienna Austria"},{"name":"The Joint Microbiome Facility of the Medical University of Vienna and the University of Vienna  Vienna 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