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

Study information

Reviewed Marked as Reviewed by Svetlana up on 2025-4-24

study design

prospective cohort

Citation

PMID PubMed identifier for scientific articles.

40214782

DOI Digital object identifier for electronic documents.

10.1007/s00394-025-03668-z

URI Uniform resource identifier for web resources.

Authors

Koponen K, McDonald D, Jousilahti P, Meric G, Inouye M, Lahti L, Niiranen T, Männistö S, Havulinna A, Knight R, Salomaa V

Journal

European journal of nutrition

Year

2025

Keywords:

Alcohol, Epidemiology, Gut microbiome, Prospective

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.

Experiment 1

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Reviewed Marked as Reviewed by Svetlana up on 2025-4-24

Curated date: 2025/04/13

Curator: Montana-D

Revision editor(s): Montana-D, Shulamite, KateRasheed

Subjects

Location of subjects: Finland

Host species Species from which microbiome was sampled. Contact us to have more species added.: Homo sapiens

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Alcohol consumption measurement Alcohol consumption measurement,alcohol consumption measurement

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Low alcohol intake

Group 1 name Corresponds to the case (exposed) group for case-control studies: High alcohol intake

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Individuals categorized as high-risk consumers of alcohol in Model 2

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): 6 months

Lab analysis

Sequencing type: WMS

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: Not specified

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: centered log-ratio

Statistical test: Linear Regression

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: Yes

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment: age, body mass index, diet, sex, smoking status, Confounders controlled for: "medication use" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.medication use

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness: decreased

Signature 1

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Curator: Montana-D

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Source: Table 2, Supplementary Table 1.

Description: Differentially abundant taxa of top 10 species in model 2. For a comprehensive listing of all significant species-level results in the fully adjusted model please see Supplemental Table 1.

Abundance in Group 1: increased abundance in High alcohol intake

NCBI	Quality Control	Links
Bacteroides cellulosilyticus
Tidjanibacter inops ATidjanibacter inops A
Parabacteroides B 862.066Parabacteroides B 862.066

Revision editor(s): Montana-D

Signature 2

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Source: Table 2, Supplementary Table 1.

Description: Differentially abundant taxa of top 10 species in model 2.

For a comprehensive listing of all significant species-level results in the fully adjusted model please see Supplemental Table 1.

Abundance in Group 1: decreased abundance in High alcohol intake

NCBI	Quality Control	Links
Acinetobacter johnsonii
Bifidobacterium bifidum
Cryptobacteroides sp900316045Cryptobacteroides sp900316045
RUG705 sp900551455RUG705 sp900551455
PeH17 sp000435055PeH17 sp000435055
SFMI01 sp004556155SFMI01 sp004556155
CAG-313 sp003539625CAG-313 sp003539625

Revision editor(s): Montana-D