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

AbstractFatty liver disease is the most common liver disease in the world. It is characterized by a buildup of excess fat in the liver that can lead to cirrhosis and liver failure. The link between fatty liver disease and gut microbiome has been known for at least 80 years. However, 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 in Finland. 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 our validation set, consisting of 30% of the data not used in model training, with an average AUC of 0.75. In addition to age and sex, our models included differences in 11 microbial groups from class Clostridia, mostly belonging to orders Lachnospirales and Oscillospirales. Pathway analysis of representative genomes of the FLI-associated taxa in (NCBI) Clostridium subclusters IV and XIVa indicated the presence of e.g., ethanol fermentation pathways. Through modeling the fatty liver index, our results provide with high resolution associations between gut microbiota composition and fatty liver in a large representative population cohort and support the role of endogenous ethanol producers in the development of fatty liver.