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To address this, we utilized a physiologically relevant long\u2010term mouse model, administering 20% EtOH in drinking water for 60\u2009weeks, to investigate the integrated consequences of chronic exposure. EtOH\u2010consuming mice (0.4\u20130.5\u2009mL\/day) exhibited &gt;\u200930% reductions in chow and fluid intake, resulting in a 12% decrease in total caloric intake compared to controls (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). Body mass remained similar until Week 52, after which EtOH\u2010treated mice had lower body mass due to reductions in both lean and fat mass (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009\u2264\u20090.004). Functional assessments revealed impaired treadmill endurance (\u221217%) and grip strength (\u221211%) (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009\u2264\u20090.037), while motor coordination remained unaffected (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.203). Chronic EtOH exposure significantly altered gut microbiota composition, reducing\n                    <jats:italic>Lactobacillus<\/jats:italic>\n                    and enriching\n                    <jats:italic>Faecalibaculum<\/jats:italic>\n                    ,\n                    <jats:italic>Clostridium<\/jats:italic>\n                    , and\n                    <jats:italic>Bifidobacterium<\/jats:italic>\n                    at the genus level. These changes were accompanied by marked depletion of short\u2010chain fatty acids (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009\u2264\u20090.05). Indirect markers of gut permeability (serum LPS &amp; zonulin) and liver injury (serum ALT &amp; AST, hepatic amyloid content) were elevated, alongside increased total cholesterol and &gt;\u200962% upregulation of hepatic TNF\u03b1, IL\u20106 &amp; serum amyloid A (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009\u2264\u20090.046). EtOH also induced dyslipidemia and glucose intolerance (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009\u2264\u20090.041), although transcriptomic changes in white adipose tissue were minimal despite elevated free fatty acids. In conclusion, chronic EtOH consumption disrupts energy balance, compromises gut barrier integrity, and impairs hepatic metabolism, collectively driving systemic and metabolic dysfunction. These findings underscore the gut\u2010liver axis as a key mediator of EtOH\u2010induced pathology and highlight the gut microbiome as a promising therapeutic target.\n                  <\/jats:p>","DOI":"10.1002\/cph4.70132","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T06:05:57Z","timestamp":1774591557000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Systemic Consequences of Chronic Ethanol Intake: From Microbiome Shifts to Metabolic Impairment"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0007-5630","authenticated-orcid":false,"given":"Muni Swamy","family":"Ganjayi","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Heritage College of Osteopathic Medicine Ohio University  Athens Ohio USA"},{"name":"Ohio Musculoskeletal and Neurological Institute Ohio University  Athens Ohio 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