Associations of alcohol with the human gut microbiome and prospective health outcomes in the FINRISK 2002 cohort

被引：0

作者：

Kari Koponen ^{[1
]}

Daniel McDonald ^{[2
]}

Pekka Jousilahti ^{[3
]}

Guillaume Meric ^{[1
]}

Michael Inouye ^{[4
]}

Leo Lahti ^{[5
]}

Teemu Niiranen ^{[6
]}

Satu Männistö ^{[7
]}

Aki Havulinna ^{[4
]}

Rob Knight ^{[8
]}

Veikko Salomaa ^{[9
]}

机构：

[1] Department of Public Health and Welfare, Finnish Institute for Health and Welfare (THL), P.O. Box 30, Helsinki

[2] Department of Bacteriology and Immunology, University of Helsinki, Helsinki

[3] Department of Pediatrics, University of California San Diego, La Jolla, San Diego, CA

[4] Cambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne

[5] Department of Infectious Diseases, Central Clinical School, Monash University, Melbourne

[6] Department of Cardiovascular Research, Translation, and Implementation, La Trobe University, Melbourne, VIC

[7] Department of Cardiometabolic Health, University of Melbourne, Melbourne, VIC

[8] Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge

[9] Department of Computing, University of Turku, Turku

[10] Department of Medicine, Turku University Hospital and University of Turku, Turku

[11] Institute for Molecular Medicine Finland, Helsinki

[12] Center for Microbiome Innovation, University of California San Diego, La Jolla, San Diego, CA

[13] Department of Computer Science & Engineering, University of California San Diego, La Jolla, San Diego, CA

[14] Shu Chien - Gene Lay Department of Bioengineering, University of California San Diego, La Jolla, San Diego, CA

[15] Halıcıoğlu Data Science Institute, University of California San Diego, La Jolla, San Diego, CA

来源：

European Journal of Nutrition | 2025年 / 64卷 / 4期

关键词：

Alcohol; Epidemiology; Gut microbiome; Prospective;

D O I：

10.1007/s00394-025-03668-z

中图分类号：

学科分类号：

摘要：

BACKGROUND AND AIMS: Alcohol remains a global risk factor for non-communicable diseases with the gut microbiome emerging as a novel elucidator. 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. METHODS: 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. RESULTS: High-risk alcohol consumers had significantly lower bacterial diversity when compared to low-risk consumers (mean±SD:4.04±0.41 vs. 4.11±0.43, p = 9.56 × 10- 4). Alcohol also associated with significant shifts in overall composition (PERMANOVA; p ≤ 1.00 × 10- 4) and differential abundances of 344 species (ANCOM-BC2; q ≤ 0.05). These shifts were characterized by an increase in relative abundances of Gram-negative bacteria, the top genera of which were Bacteroides and Prevotella, and a decrease in putatively beneficial species in genera such as Lactobacillus, Bifidobacterium, and Akkermansia. Prospective associations with all-cause mortality (HR:1.12 [1.02-1.23]), and liver disease (HR:1.53 [1.22-1.92]) were observed. The association between alcohol and liver disease had a mediating link via a proinflammatory beta-diversity principal coordinate (OR:1.04 [1.001-1.10]). Functional associations were observed with 1643 KO-groups (q < 0.05, npositive=431, nnegative=1212). Antioxidative and gut integrity maintaining functions were diminished and lipopolysaccharide synthesis enriched. CONCLUSIONS: 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's effect on incident liver disease risk, possibly via increased proliferation of endotoxins through the gut epithelial lining. © 2025. The Author(s).

引用