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We investigated how gut microbiome associates with alcohol on population level, if there is mediation reflected in health outcomes, and how functional potential is related.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Our sample consisted of 4575 shallow-shotgun sequenced fecal samples from the FINRISK 2002 cohort (25-74yrs., 52.5% women). Alcohol (g 100% alcohol\/week) use was self-reported. Diversity and differential species abundances were analyzed using multiple linear regression. Compositional differences were analyzed using PERMANOVA, and prospective associations with Cox-regression. Connections between alcohol, microbiome, inflammatory markers, and outcomes were assessed using serial mediation. Functional associations were assessed using KEGG-orthologies and multiple linear regression.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>High-risk alcohol consumers had significantly lower bacterial diversity when compared to low-risk consumers (mean\u00b1SD:4.04\u00b10.41 vs. 4.11\u00b10.43, <jats:italic>p<\/jats:italic>\u2009=\u20099.56\u2009\u00d7\u200910<jats:sup>\u2212\u20094<\/jats:sup>). Alcohol also associated with significant shifts in overall composition (PERMANOVA; <jats:italic>p<\/jats:italic>\u2009\u2264\u20091.00\u2009\u00d7\u200910<jats:sup>\u2212\u20094<\/jats:sup>) and differential abundances of 344 species (ANCOM-BC2; q\u2009\u2264\u20090.05). These shifts were characterized by an increase in relative abundances of Gram-negative bacteria, the top genera of which were <jats:italic>Bacteroides<\/jats:italic> and <jats:italic>Prevotella<\/jats:italic>, and a decrease in putatively beneficial species in genera such as <jats:italic>Lactobacillus<\/jats:italic>, <jats:italic>Bifidobacterium<\/jats:italic>, and<jats:italic> Akkermansia<\/jats:italic>. Prospective associations with all-cause mortality (HR:1.12 [1.02\u20141.23]), and liver disease (HR:1.53 [1.22\u20141.92]) were observed. The association between alcohol and liver disease had a mediating link via a proinflammatory beta-diversity principal coordinate (OR:1.04 [1.001\u20141.10]). Functional associations were observed with 1643 KO-groups (q\u2009&lt;\u20090.05, n<jats:sub>positive<\/jats:sub>=431, n<jats:sub>negative<\/jats:sub>=1212). Antioxidative and gut integrity maintaining functions were diminished and lipopolysaccharide synthesis enriched.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Alcohol use is associated with community-level shifts in composition towards enriched Gram-negative bacteria, and diminished levels of putatively beneficial bacteria. Alcohol use associates with a proinflammatory gut microbiome profile that mediates alcohol\u2019s effect on incident liver disease risk, possibly via increased proliferation of endotoxins through the gut epithelial lining.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s00394-025-03668-z","type":"journal-article","created":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T11:46:01Z","timestamp":1744371961000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Associations of alcohol with the human gut microbiome and prospective health outcomes in the FINRISK 2002 cohort"],"prefix":"10.1007","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0417-107X","authenticated-orcid":false,"given":"Kari","family":"Koponen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0876-9060","authenticated-orcid":false,"given":"Daniel","family":"McDonald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7190-0979","authenticated-orcid":false,"given":"Pekka","family":"Jousilahti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6288-9958","authenticated-orcid":false,"given":"Guillaume","family":"Meric","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9413-6520","authenticated-orcid":false,"given":"Michael","family":"Inouye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5537-637X","authenticated-orcid":false,"given":"Leo","family":"Lahti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7394-7487","authenticated-orcid":false,"given":"Teemu","family":"Niiranen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8668-3046","authenticated-orcid":false,"given":"Satu","family":"M\u00e4nnist\u00f6","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4787-8959","authenticated-orcid":false,"given":"Aki","family":"Havulinna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7531-0087","authenticated-orcid":false,"given":"Rob","family":"Knight","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7563-5324","authenticated-orcid":false,"given":"Veikko","family":"Salomaa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,11]]},"reference":[{"key":"3668_CR1","unstructured":"WHO (World Health Organization). 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