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Links between gut microbiome composition and fatty liver disease in a large population sample.

ABSTRACT: Fatty liver disease is the most common liver disease in the world. Its connection with the gut microbiome has been known for at least 80 y, but this association remains mostly unstudied in the general population because of underdiagnosis and small sample sizes. To address this knowledge gap, we studied the link between the Fatty Liver Index (FLI), a well-established proxy for fatty liver disease, and gut microbiome composition in a representative, ethnically homogeneous population sample of 6,269 Finnish participants. We based our models on biometric covariates and gut microbiome compositions from shallow metagenome sequencing. Our classification models could discriminate between individuals with a high FLI (≥60, indicates likely liver steatosis) and low FLI (<60) in internal cross-region validation, consisting of 30% of the data not used in model training, with an average AUC of 0.75 and AUPRC of 0.56 (baseline at 0.30). In addition to age and sex, our models included differences in 11 microbial groups from class Clostridia, mostly belonging to orders Lachnospirales and Oscillospirales. Our models were also predictive of the high FLI group in a different Finnish cohort, consisting of 258 participants, with an average AUC of 0.77 and AUPRC of 0.51 (baseline at 0.21). Pathway analysis of representative genomes of the positively FLI-associated taxa in (NCBI) Clostridium subclusters IV and XIVa indicated the presence of, e.g., ethanol fermentation pathways. These results support several findings from smaller case-control studies, such as the role of endogenous ethanol producers in the development of the fatty liver.

SUBMITTER: Ruuskanen MO

PROVIDER: S-EPMC7928040 | biostudies-literature | 2021 Jan-Dec

REPOSITORIES: biostudies-literature

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Links between gut microbiome composition and fatty liver disease in a large population sample.

Ruuskanen Matti O MO Åberg Fredrik F Männistö Ville V Havulinna Aki S AS Méric Guillaume G Liu Yang Y Loomba Rohit R Vázquez-Baeza Yoshiki Y Tripathi Anupriya A Valsta Liisa M LM Inouye Michael M Jousilahti Pekka P Salomaa Veikko V Jain Mohit M Knight Rob R Lahti Leo L Niiranen Teemu J TJ

Gut microbes 20210101 1

Fatty liver disease is the most common liver disease in the world. Its connection with the gut microbiome has been known for at least 80 y, but this association remains mostly unstudied in the general population because of underdiagnosis and small sample sizes. To address this knowledge gap, we studied the link between the Fatty Liver Index (FLI), a well-established proxy for fatty liver disease, and gut microbiome composition in a representative, ethnically homogeneous population sample of 6,26 ...[more]

PMID: 33651661

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Project description:BackgroundMany studies have shown that carotenoids are beneficial to non-alcoholic fatty liver disease (NAFLD). Therefore, we explored potential biomarkers of gut microbiota and fecal and serum metabolites linking the association between serum carotenoids and NAFLD in adults.MethodsThis 7.8-year prospective study included 2921 participants with serum carotenoids at baseline and determined NAFLD by ultrasonography (ULS-NAFLD) every 3 years. A total of 828 subjects additionally underwent magnetic resonance imaging to identify NAFLD (MRI-NAFLD). Gut microbiota was analyzed by 16S rRNA sequencing in 1,661 participants, and targeted metabolomics profiling in 893 feces and 896 serum samples was performed by ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) in the middle term.ResultsA total of 2,522 participants finished follow-up visits. Of these participants, 770, 301, 474, and 977 were categorized into NAFLD-free, improved, new-onset, and persistent NAFLD groups based on their ULS-NAFLD status changes, respectively, and 342/828 were MRI-verified NALFD. Longitudinal analyses showed an inverse association between carotenoids and NALFD risk/presence (P-trend <0.05). Multivariable-adjusted odds ratios (ORs)/hazard ratio (HR) [95% confidence intervals (CIs)] of NAFLD for quartile 4 (vs. quartile 1) of total carotenoids were 0.63 (0.50, 0.80) for incident ULS-NAFLD, 0.20 (0.15, 0.27) for persistent ULS-NAFLD, 1.53 (1.10, 2.12) for improved-NAFLD, and 0.58 (0.39, 0.87) for MRI-NAFLD. The biomarkers in the gut-liver axis significantly associated with both serum carotenoids and NAFLD included sixteen microbial genera mainly in Ruminococcaceae and Veillonellaceae family, nineteen fecal metabolites containing medium-chain fatty acids (MCFAs), bile acids, and carnitines, and sixteen serum metabolites belonging to organic acids and amino acids. The total carotenoids-related scores of significant microbial genera, fecal and serum metabolites mediated the carotenoids-NAFLD association by 8.72%, 12.30%, and 16.83% (all P<0.05) for persistent NAFLD and 9.46%, 8.74%, and 15.7% for incident-NAFLD, respectively.ConclusionsOur study reveals a beneficial association of serum carotenoids and incident and persistent NAFLD. The identified gut-liver axis biomarkers provided mechanistic linkage for the epidemiological association.

Dataset Information

Links between gut microbiome composition and fatty liver disease in a large population sample.

Publications

Links between gut microbiome composition and fatty liver disease in a large population sample.

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