Gut microbiota dysbiosis rewires host mRNA m6A epitranscriptomic landscape via bile acid metabolism

Gut microbiota and their metabolites influence host gene expression and physiological status through diverse mechanisms. Here we investigate how gut microbiota and their metabolites impact host's mRNA m6A epitranscriptome in various antibiotic-induced microbiota dysbiosis models. With multi-omics analysis, we find that the imbalance of gut microbiota can rewire host mRNA m6A epitranscriptomic profiles in brain, liver and intestine. We further explore the underlying mechanisms regulating host mRNA m6A methylome by depleting the microbiota with ampicillin. Metabolomic profiling shows that cholic acids are the main down-regulated metabolites with Firmicutes as the most significantly reduced genus in ampicillin-treated mice comparing to untreated mice. Fecal microbiota transplantations in germ-free mice and metabolites supplementations in cells verify that cholic acids are associated with host mRNA m6A epitranscriptomic rewiring. Collectively, this study employs an integrative multi-omics analysis to demonstrate the impact of gut microbiota dysbiosis on host mRNA m6A epitranscriptomic landscape via cholic acid metabolism. Overall design: Mice were fed water with different antibiotics to form mouse models with different intestinal flora. MeRIP-seq, Proteome, RNA-seq, 16S rDNA and Metabolome of mouse tissues were used to study the effects of intestinal microbiota and its metabolites on host epigenetic modifications, protein expression, and regulation of gene expression. The 102 samples in the current dataset are all RNA sequencing datasets.