Mendelian randomization suggests a causal relationship between gut microbiota and nonalcoholic fatty liver disease in humans

Abstract

Targeting the gut microbiota is an emerging strategy to treat nonalcoholic fatty liver disease (NAFLD). Nonetheless, the causal relationship between specific gut microbiota and NAFLD remains unclear. We first obtained genome-wide association study statistics on gut microbiota and NAFLD from publicly available databases. We then performed the Mendelian randomization (MR) analysis to determine the potential causal relationship between the gut microbiota and NAFLD by 5 different methods, and conducted a series of sensitivity analyses to validate the robustness of the MR analysis results. Furthermore, we investigated the direction of causality by bidirectional MR analysis. For 211 gut microbiota, 2 MR methods confirmed that phylum Tenericutes, class Deltaproteobacteria and class Mollicutes were significantly associated with the risk of NAFLD. Heterogeneity (P > .05) and pleiotropy (P > .05) analyses validated the robustness of the MR results. There was no causal effect of NAFLD on these bacterial taxa in the reverse MR analysis. We identified specific gut microbiota with causal effects on NAFLD through gene prediction, which may provide useful guidance for targeting the gut microbiota to intervene and treat NAFLD.