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Here, we investigated the impact of mouse vendor on indomethacin-induced injury using C57BL\/6 mice from different breeding facilities (in-house \u201cTar Heel\u201d and commercial Charles River). We found that Tar Heel mice exhibited significantly enhanced susceptibility to indomethacin toxicity, characterized by greater body weight loss, increased ileal ulceration, elevated fecal lipocalin-2 levels, and higher goblet cell numbers in ileum compared to Charles River mice.<\/jats:p>\n                <jats:p>Importantly, whole genome metagenomic analysis revealed distinct baseline gut microbiomes between the two types of mice. Notably, Tar Heel mice showed higher abundances of \u03b2-glucuronidase (GUS)-producing bacteria, particularly those expressing Loop-1 GUS enzymes, and elevated levels of mucolytic enzyme-encoding bacteria. These differences suggest that enhanced indomethacin toxicity observed in Tar Heel mice may be related to functional changes in their gut microbiome, which may predispose to an exaggerated response to NSAID exposure. Together, our findings demonstrate that vendor-specific differences significantly influence NSAID-induced intestinal toxicity and highlight the importance of considering mouse sources and gut microbial compositions in experimental design. Moreover, we highlight potential functional roles that gut microbes play in host-indomethacin interactions.<\/jats:p>","DOI":"10.1101\/2025.05.01.651704","type":"posted-content","created":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T07:00:24Z","timestamp":1746169224000},"source":"Crossref","is-referenced-by-count":0,"title":["Commercially Purchased and In-House Bred C57BL\/6 Mice with Different Gut Microbiota Exhibit Distinct Indomethacin-Induced Toxicities"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9801-2779","authenticated-orcid":false,"given":"Jianan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rose Viguna","family":"Thomas Backet","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5439-491X","authenticated-orcid":false,"given":"Josh J.","family":"Sekela","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7920-8005","authenticated-orcid":false,"given":"Meredith J.","family":"Zeller","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8870-4675","authenticated-orcid":false,"given":"Rani S.","family":"Sellers","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0814-5346","authenticated-orcid":false,"given":"Matthew R.","family":"Redinbo","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA"},{"name":"Departments of Biochemistry and Biophysics, Microbiology and Immunology, and Integrated Program in Biological and Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7612-6369","authenticated-orcid":false,"given":"Ajay S.","family":"Gulati","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA"},{"name":"Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0134-6543","authenticated-orcid":false,"given":"Aadra P.","family":"Bhatt","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041206223339000_2025.05.01.651704v1.1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1018832902287"},{"key":"2026041206223339000_2025.05.01.651704v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gtc.2009.03.007"},{"key":"2026041206223339000_2025.05.01.651704v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2020.114147"},{"key":"2026041206223339000_2025.05.01.651704v1.4","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.01153"},{"key":"2026041206223339000_2025.05.01.651704v1.5","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.679396"},{"key":"2026041206223339000_2025.05.01.651704v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2016.08.002"},{"key":"2026041206223339000_2025.05.01.651704v1.7","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.7b00139"},{"key":"2026041206223339000_2025.05.01.651704v1.8","doi-asserted-by":"crossref","unstructured":"Ok, M.T. , et al. 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