Gut microbiota in a mouse model with different intestinal flora dysbiosis

The gut microbiota and its metabolites affect host gene expression and physiological status through multiple mechanisms. Here, we investigated how the gut microbiota and its metabolites affect the host mRNA m6A epigenome in various antibiotic-induced microbiota disorder models. Through multi-omics analysis, we found that imbalance of gut microbiota can reconstruct the host mRNA m6A episodic transcriptome profile in brain, liver and intestine. We further explored potential mechanisms to regulate the host mRNA m6A methylome through ampicillin-depleted microbiota. Metabolomic analysis revealed that bile acids were the major down-regulated metabolite, with the thick-walled phylum being the most significantly reduced phylum in ampicillin-treated mice compared to untreated mice. Fecal microbiota transplantation and metabolite replenishment in germ-free mice confirmed that bile acids are associated with epigenetic transcriptome reorganization of host mRNA m6A. In conclusion, this study used a comprehensive multi-omics analysis to demonstrate the effect of gut microbiota dysbiosis on host mRNA m6A episodic transcriptome profiling through bile acid metabolism.