{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T19:21:57Z","timestamp":1793992917680,"version":"4.8.0"},"reference-count":30,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T00:00:00Z","timestamp":1756944000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Scientific Research Projects Coordination Unit of Dokuz Eyl\u00fcl University","award":["TKB-2022-2664"],"award-info":[{"award-number":["TKB-2022-2664"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) encompasses a spectrum of liver conditions and involves gut\u2013liver axis crosstalk. We aimed to evaluate whether oral vancomycin modifies liver injury and the cecal microbiota in a methionine\u2013choline-deficient (MCD) diet model of NASH. Male C57BL\/6J mice (n = 28) were block-randomized to four groups (n = 7 each) for 10 weeks: standard diet (STD); MCD diet; STD + vancomycin (VANC); and MCD + VANC (2 mg\/mouse \u2248 50 mg\/kg, every 72 h). After 10 weeks, liver tissues were analyzed for histological changes, cytokine levels [interleukin-6 (IL-6), interleukin-8 (IL-8), transforming growth factor beta 1 (TGF-\u03b21)], and immunohistochemical markers [ubiquitin and cytokeratin 18 (CK18)]. Cecal microbiota composition was evaluated with 16S ribosomal RNA (rRNA) sequencing. The MCD reproduced key NASH features (macrovesicular steatosis, lobular inflammation). Vancomycin shifted steatosis toward a microvesicular pattern and reduced hepatocyte injury: CK18 and ubiquitin immunoreactivity were decreased in MCD + VANC vs. MCD, and hepatic IL-8 and TGF-\u03b21 levels were lower in MCD + VANC vs. STD. Taxonomically, STD mice had Lactobacillus-rich microbiota. The MCD diet alone reduced alpha diversity (\u03b1-diversity), modestly lowered Firmicutes and increased Desulfobacterota\/Fusobacteriota. Vancomycin alone caused a much larger collapse in richness, depleting Gram-positive commensals and promoting blooms of Escherichia\u2013Shigella, Klebsiella, Parabacteroides, and Akkermansia. In the MCD + VANC group, vancomycin profoundly remodeled the microbiota, eliminating key commensals (e.g., Lactobacillus) and enriching Desulfobacterota, Fusobacteriota, and Campylobacterota. Oral vancomycin in the MCD model of NASH improved liver injury markers and altered steatosis morphology, but concurrently reprogrammed the gut into a low-diversity, pathobiont-enriched ecosystem with near-loss of Lactobacillus. These findings highlight a therapeutic trade-off\u2014hepatic benefit accompanied by microbiome cost\u2014that should guide microbiota-targeted strategies for NAFLD\/NASH.<\/jats:p>","DOI":"10.3390\/ijms26178616","type":"journal-article","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T07:46:17Z","timestamp":1757058377000},"page":"8616","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Hepatic Histopathological Benefit, Microbial Cost: Oral Vancomycin Mitigates Non-Alcoholic Fatty Liver Disease While Disrupting the Cecal Microbiota"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3829-4978","authenticated-orcid":false,"given":"G\u00fcl","family":"\u00c7irkin","sequence":"first","affiliation":[{"name":"Department of Pediatric Gastroenterology Hepatology and Nutrition, Faculty of Medicine, Dokuz Eylul University, Izmir 35340, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selma","family":"Aydemir","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, Dokuz Eylul University, Izmir 35340, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7245-7697","authenticated-orcid":false,"given":"Burcu","family":"A\u00e7\u0131kg\u00f6z","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Dokuz Eylul University, Izmir 35340, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asl\u0131","family":"\u00c7elik","sequence":"additional","affiliation":[{"name":"Experimental Animals Laboratory, Faculty of Medicine, Dokuz Eylul University, Izmir 35340, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunus","family":"G\u00fcler","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology Hepatology and Nutrition, Faculty of Medicine, Dokuz Eylul University, Izmir 35340, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00fcge","family":"Kiray","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Dokuz Eylul University, Izmir 35340, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ba\u015fak","family":"Baykara","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, Dokuz Eylul University, Izmir 35340, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ener \u00c7a\u011fr\u0131","family":"Dinleyici","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir 26040, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye\u015fim","family":"\u00d6zt\u00fcrk","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology Hepatology and Nutrition, Faculty of Medicine, Dokuz Eylul University, Izmir 35340, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1111\/liv.13301","article-title":"Pathology of non-alcoholic fatty liver disease","volume":"37","author":"Bedossa","year":"2017","journal-title":"Liver Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.jhep.2020.03.039","article-title":"A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement","volume":"73","author":"Eslam","year":"2020","journal-title":"J. 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