{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T02:43:25Z","timestamp":1790909005106,"version":"4.1.0"},"reference-count":57,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFF1103702"],"award-info":[{"award-number":["2023YFF1103702"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2017YF0400303"],"award-info":[{"award-number":["2017YF0400303"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Jinan \u201c20 New Universities\u201d funding project","award":["202228040"],"award-info":[{"award-number":["202228040"]}]},{"name":"Tianjin Science and Technology Achievement Transfer and Transformation Project","award":["24ZYCGSY00390"],"award-info":[{"award-number":["24ZYCGSY00390"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Acute alcohol intoxication causes liver injury and delays recovery via oxidative stress, ferroptosis, inflammation, and gut dysbiosis. This study investigated whether pretreatment with an Alcohol Relief Formula (ARF), composed of soybean peptides, botanical extracts, and probiotics, protects against alcohol-induced liver damage in a preventive model and explored the underlying mechanisms. Methods: Mice with acute alcohol intoxication were pretreated with ARF. Liver damage, hepatic alcohol-metabolizing enzymes, antioxidant capacity, inflammatory cytokines, and lipid peroxidation were measured. Ferroptosis markers and AMP-activated protein kinase (AMPK) signaling were assessed. Gut microbiota composition and cecal short-chain fatty acids (SCFAs) were analyzed. Correlations between SCFAs, ferroptosis suppression, and AMPK activation were evaluated. Results: ARF pretreatment alleviated acute liver damage and accelerated sobriety. It enhanced alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activities, inhibited CYP2E1 expression, and improved alcohol metabolism. ARF pretreatment restored antioxidant capacity, decreased pro-inflammatory cytokines and lipid peroxidation, and ameliorated hepatic histopathological changes. Notably, ARF pretreatment was associated with suppressed ethanol-induced ferroptosis markers, including increased glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and ferroptosis suppressor protein 1 (FSP1) expression, elevated AMPK phosphorylation, and reduced hepatic total iron content. In parallel, ARF pretreatment was associated with modulation of the alcohol-disrupted gut microbiota, increased short-chain fatty acid (SCFA)-producing bacteria, and maintained cecal acetate, propionate, and butyrate levels. Correlation analysis revealed that SCFA restoration was positively associated with ferroptosis marker modulation and AMPK activation, suggesting a potential link between gut metabolites and hepatic protection. Conclusions: ARF may serve as a potential preventive nutritional strategy for acute alcohol intoxication by promoting recovery and mitigating liver damage in this acute binge pretreatment model. The observed effects may involve the modulation of gut microbiota-derived SCFAs and AMPK signaling associated with ferroptosis markers.<\/jats:p>","DOI":"10.3390\/nu18172790","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T15:04:32Z","timestamp":1787756672000},"page":"2790","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Probiotic\u2013Herb\u2013Peptide Combined Formula Alleviates Alcoholic Liver Damage Associated with Modulation of the Gut\u2013Liver Axis and Ferroptosis"],"prefix":"10.3390","volume":"18","author":[{"given":"Yining","family":"Wang","sequence":"first","affiliation":[{"name":"Key Laboratory of Industrial Fermentation Microbiology of the Ministry of Education and Tianjin Key Laboratory of Industrial Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyang","family":"Tong","sequence":"additional","affiliation":[{"name":"Key Laboratory of Industrial Fermentation Microbiology of the Ministry of Education and Tianjin Key Laboratory of Industrial Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weilong","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Industrial Fermentation Microbiology of the Ministry of Education and Tianjin Key Laboratory of Industrial Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7923-6758","authenticated-orcid":false,"given":"Chao","family":"Huo","sequence":"additional","affiliation":[{"name":"Key Laboratory of Industrial Fermentation Microbiology of the Ministry of Education and Tianjin Key Laboratory of Industrial Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuegang","family":"Luo","sequence":"additional","affiliation":[{"name":"Key Laboratory of Industrial Fermentation Microbiology of the Ministry of Education and Tianjin Key Laboratory of Industrial Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1053\/j.gastro.2011.09.002","article-title":"Alcoholic Liver Disease: Pathogenesis and New Therapeutic Targets","volume":"141","author":"Gao","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_2","unstructured":"World Health Organization (2018). 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