Murine fecal microRNAs alter the composition of cultured gut microbiota

Fecal microRNAs (miRNAs) derived from intestinal epithelial cells have been suggested to influence gut microbiota homeostasis. The present study examined whether fecal miRNAs alter the structure of cultured gut microbiota. Fecal bacteria isolated from murine cecal contents were cultured for 24 h under anaerobic conditions. Supplementation with fecal small RNAs isolated from cecal contents altered the structure of cultured fecal microbiota as assessed by 16S rRNA gene sequence analysis. In particular, fecal small RNAs increased Enterococcus spp. Fractionation of fecal small RNAs by ultrafiltration showed that small RNAs smaller than 10 kDa significantly increased enterococci compared to those larger than 10 kDa, as assessed by quantitative PCR, suggesting that the increase in enterococci by fecal small RNAs can mainly be attributed to miRNAs. Negative control miRNA that has low homology to miRNA sequences of human, mouse, and rat, failed to increase enterococci. Therefore, the findings from the present study employing cultured fecal bacteria suggest that fecal small RNAs, most likely host-derived miRNAs, alter gut microbiota structure by expanding enterococci in a sequence-dependent manner.