A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Associations of alcohol with the human gut microbiome and prospective health outcomes in the FINRISK 2002 cohort
Tekijät: Koponen, Kari; McDonald, Daniel; Jousilahti, Pekka; Meric, Guillaume; Inouye, Michael; Lahti, Leo; Niiranen, Teemu; Männistö, Satu; Havulinna, Aki; Knight, Rob; Salomaa, Veikko
Kustantaja: Springer Science and Business Media LLC
Kustannuspaikka: HEIDELBERG
Julkaisuvuosi: 2025
Journal: European Journal of Nutrition
Tietokannassa oleva lehden nimi: European Journal of Nutrition
Lehden akronyymi: EUR J NUTR
Artikkelin numero: 153
Vuosikerta: 64
Numero: 4
Sivujen määrä: 12
ISSN: 1436-6207
eISSN: 1436-6215
DOI: https://doi.org/10.1007/s00394-025-03668-z
Verkko-osoite: https://doi.org/10.1007/s00394-025-03668-z
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/491753942
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 x 10(- 4)). Alcohol also associated with significant shifts in overall composition (PERMANOVA; p <= 1.00 x 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, n(positive)=431, n(negative)=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.
Ladattava julkaisu This is an electronic reprint of the original article. |
Julkaisussa olevat rahoitustiedot:
Open Access funding provided by University of Helsinki (including Helsinki University Central Hospital).
KK was supported by the Aarne Koskelo Foundation and the Yrjö Jahnsson Foundation. TN has received grants from the Finnish Research Council, the Sigrid Jusélius Foundation, and the Finnish Foundation for Cardiovascular Research. VS was supported by the Juho Vainio Foundation.