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Arginine is a conditionally essential amino acid that may play a key role in maintaining redox homeostasis and mediating host\u2013microbiota crosstalk. We hypothesized that supplemental arginine provided during chronic ethanol exposure in mice would mitigate oxidative damage via the gut\u2013liver axis. Our findings suggest that arginine supplementation mediated hepatic steatosis, preserved body weight and fat, and reduced oxidative stress in the gut\u2013liver axis. These changes were associated with alterations in gut microbiota composition and function. These data support a potential role for arginine supplementation in mitigating ethanol-induced oxidative damage via the gut\u2013liver axis.<\/jats:p>","DOI":"10.3390\/antiox15050537","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T11:40:12Z","timestamp":1777981212000},"page":"537","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Role of L-Arginine in the Gut\u2013Liver Axis of Female Mice: Mediating Ethanol\u2019s Alterations in Hepatic Steatosis and Oxidative Stress"],"prefix":"10.3390","volume":"15","author":[{"given":"Kaitlyn","family":"Daff","sequence":"first","affiliation":[{"name":"Department of Microbial Sciences in Health, Cleveland Clinic Research, Cleveland, OH 44195, USA"},{"name":"Department of Nutrition, Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1937-7871","authenticated-orcid":false,"given":"Yingchun","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Microbial Sciences in Health, Cleveland Clinic Research, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2795-3122","authenticated-orcid":false,"given":"Zhuoying","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Microbial Sciences in Health, Cleveland Clinic Research, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0591-6515","authenticated-orcid":false,"given":"Mala","family":"Upadhyay","sequence":"additional","affiliation":[{"name":"Department of Microbial Sciences in Health, Cleveland Clinic Research, Cleveland, OH 44195, USA"},{"name":"Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vyshnavi","family":"Sivampeta","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8074-6721","authenticated-orcid":false,"given":"Abirami","family":"Rajasekaran","sequence":"additional","affiliation":[{"name":"Department of Microbial Sciences in Health, Cleveland Clinic Research, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naseer","family":"Sangwan","sequence":"additional","affiliation":[{"name":"Department of Microbial Sciences in Health, Cleveland Clinic Research, Cleveland, OH 44195, USA"},{"name":"Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44195, USA"},{"name":"Department of Heart, Blood and Kidney Research, Cleveland Clinic Research, Cleveland, OH 44195, USA"},{"name":"Microbial Sequencing & Analytics Resource (MSAAR) Facility, Shared Laboratory Resources (SLR), Cleveland Clinic Research, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5717-7099","authenticated-orcid":false,"given":"Gail A. 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