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This research aims to investigated the physiological mechanism of a high salt diet (HSD) enhanced antibiotic-induced hepatic injury and mitochondrial abnormalities in mice. The mice were fed a HSD with or without penicillin G (PEN) for 8\u00a0weeks and the gut metabolome, untargeted faecal metabolomics, and intestinal function were evaluated. The results revealed that HSD, PEN and their combination (HSPEN) significantly changed the gut microbial community. HSPEN mice exhibited more opportunistic pathogens (such as <jats:italic>Klebsiella<\/jats:italic> and <jats:italic>Morganella<\/jats:italic>) and reduced probiotic species (including <jats:italic>Bifidobacterium<\/jats:italic> and <jats:italic>Lactobacillus<\/jats:italic>). The main variations in the faecal metabolites of the HSPEN group were identified, including those connected with entero-hepatic circulation (including bile acids), tryptophan metabolism (i.e., indole derivatives) and lipid metabolism (e.g., erucic acid). Furthermore, increased intestinal permeability and immunologic response caused greater hepatic damage in the HSPEN group compared to the other groups. These findings may have important implications for public health.<\/jats:p>","DOI":"10.3389\/fphar.2022.829686","type":"journal-article","created":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T11:50:00Z","timestamp":1644580200000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Antibiotic Disruption of the Gut Microbiota Enhances the Murine Hepatic Dysfunction Associated With a High-Salt Diet"],"prefix":"10.3389","volume":"13","author":[{"given":"Zheng","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengjie","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1174","DOI":"10.1136\/gutjnl-2020-323071","article-title":"Gut Microbiota-Derived Metabolites as central Regulators in Metabolic Disorders","volume":"70","author":"Agus","year":"2021","journal-title":"Gut"},{"key":"B2","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1016\/S0022-2836(05)80360-2","article-title":"Basic Local Alignment Search Tool (BLAST)","volume":"215","author":"Altschul","year":"1990","journal-title":"J. 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