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Loss-of-function mutations in the nucleotide-binding oligomerization domain 2 gene (NOD2) are the strongest risk factor for Crohn's disease (CD); however, environmental factors affecting CD development have been poorly defined in patients with NOD2 mutations. In this study, we investigated whether high-fat diet (HFD), one of the possible environmental risk factors for CD, acts synergistically with NOD2 deficiency to promote dextran sodium sulfate (DSS)-induced colitis in mice. NOD2-intact (NOD2+\/+) and NOD2-deficient (NOD2\u2212\/\u2212) mice were challenged with DSS after exposure to normal diet (ND) or HFD. Fecal microbiota composition was determined using next-generation sequencing analyses targeting 16S ribosomal RNA. Fecal microbiota transplantation (FMT) was conducted using microbiota from ND- or HFD-fed NOD2+\/+ and NOD2-\/- mice as donors. The development of DSS-induced colitis was markedly inhibited by HFD in both NOD2+\/+ and NOD2-\/- mice, which was accompanied by reduced C-C motif chemokine ligand 2 (CCL2) and tumor necrosis factor (TNF)-a expression levels. The FMT data showed that NOD2-independent colonization by Turicimonas muris induced by HFD suppressed DSS-induced colitis via the downregulation of colonic CCL2 and TNF-a responses. These data suggest that HFD protected against DSS-induced colitis in mice with or without intact NOD2 by promoting colonization by T. muris. Although avoidance of HFD is encouraged in patients with CD, HFD might be useful in the maintenance of intestinal immune homeostasis in experimental colitis.<\/jats:p>","DOI":"10.1093\/cei\/uxag057","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T11:48:37Z","timestamp":1789040917000},"source":"Crossref","is-referenced-by-count":0,"title":["Nucleotide-binding oligomerization domain 2-independent colonization by\n                    <i>Turicimonas muris<\/i>\n                    induced by high-fat diet protects against dextran sodium sulfate-induced colitis"],"prefix":"10.1093","volume":"220","author":[{"given":"Hajime","family":"Honjo","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine , Sakai, Osaka \u00a0","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6175-8064","authenticated-orcid":false,"given":"Tomohiro","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine , Sakai, Osaka \u00a0","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuo","family":"Otsuka","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine , Sakai, Osaka \u00a0","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Masuta","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine , Sakai, Osaka \u00a0","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sho","family":"Masaki","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine , Sakai, Osaka \u00a0","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Kamata","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine , Sakai, Osaka \u00a0","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosuke","family":"Minaga","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine , Sakai, Osaka \u00a0","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4619-9345","authenticated-orcid":false,"given":"Seiichi","family":"Omura","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Kindai University Faculty of Medicine , Sakai, Osaka \u00a0","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ah-Mee","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Kindai University Faculty of Medicine , Sakai, Osaka \u00a0","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masatoshi","family":"Kudo","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine , Sakai, Osaka 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