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This study determines whether the innate microbiota of rats selectively bred for generations as high alcohol drinkers play a role in their alcohol intake. Wistar\u2010derived high\u2010drinker UChB rats (intake 10\u2010g ethanol\/kg\/day) administered nonabsorbable oral antibiotics <jats:italic>before allowing<\/jats:italic> access to alcohol, reducing their voluntary ethanol intake by 70%, an inhibition that remained after the antibiotic administration was discontinued. Oral administration of <jats:styled-content style=\"fixed-case\"><jats:italic>Lactobacillus rhamnosus<\/jats:italic><\/jats:styled-content> Gorbach\u2013Goldin (GG) induced the synthesis of FGF21, a vagal \u03b2\u2010Klotho receptor agonist, and partially re\u2010invoked a mechanism that reduces alcohol intake. The vagus nerve constitutes the main axis transferring gut microbiota information to the brain (\u201cmicrobiota\u2010gut\u2010brain\u201d axis). Bilateral vagotomy inhibited rat alcohol intake by 75%. Neither antibiotic treatment nor vagotomy affected total fluid intake. A microbiota\u2010mediated marked inflammatory environment was observed in the gut of ethanol\u2010na\u00efve high\u2010drinker rats, as gene expression of proinflammatory cytokines (TNF\u2010\u03b1; IL\u20106; IL\u20101\u03b2) was significantly reduced by nonabsorbable antibiotic administration. Gut cytokines are known to activate the vagus nerve, while vagal activation induces pro\u2010rewarding effects in nucleus accumbens. Both alcoholics and alcohol\u2010preferring rats share a marked preference for sweet tastes\u2014likely an evolutionary trait to seek sweet fermented fruits. Saccharin intake by UChB rats was inhibited by 75%\u201385% by vagotomy or oral antibiotic administration, despite saccharin\u2010induced polydipsia. Overall, data indicate that the mechanisms that normally curtail heavy drinking are inhibited in alcohol\u2010preferring animals and inform a gut microbiota origin. Whether it applies to other mammals and humans merits further investigation.<\/jats:p>","DOI":"10.1111\/adb.13018","type":"journal-article","created":{"date-parts":[[2021,1,29]],"date-time":"2021-01-29T02:25:52Z","timestamp":1611887152000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Innate gut microbiota predisposes to high alcohol consumption"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7696-4215","authenticated-orcid":false,"given":"Fernando","family":"Ezquer","sequence":"first","affiliation":[{"name":"Center for Regenerative Medicine, School of Medicine Cl\u00ednica Alemana\u2010Universidad del Desarrollo  Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Elena","family":"Quintanilla","sequence":"additional","affiliation":[{"name":"Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine 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