Short chain fatty acids-miRNA10a-5p-PI3K axis as a potential anti-colitis mechanism for fecal microbiota transplantation in mice

Fecal microbiota transplantation had been reported to have anti-colitis activity in mice, whereas the underlying mechanism that microbiota transplantation mediated the alleviation of IBD, remained unknown. The dextran sulfate sodium (DSS)-induced colitis mice were transplanted with live or heat-killed fecal microbiota for 41 days. The results indicated that transplantation of heat killed fecal microbiota partially alleviated DSS induced colitis, characterized by improved pathological phenotypes, intestinal permeability and host inflammation, as well as specific regulation effect on PI3K/Akt signaling pathway. The significantly beneficial effects of heat-killed fecal microbiota transplantation on colitis make us further focused on the anti-colitis activities of commonly detected microbiota metabolites with thermostability, including branched chain amino acids (BCAAs), bile acids (BAs) and short-chain fatty acids (SCFAs). Among them, SCFAs treatment showed the best anti-colitis activity compared to other two metabolites. Subsequently, the colonic microRNA profile response to SCFAs treatment was sequenced, miR-10a-5p was screened due to its significantly different expression among groups and its potential target gene was predicted to be PI3K. In addition, dual luciferase reporter assay was used to further confirm the direct regulation effect of miR-10a-5p on PI3K expression. Collectively, these findings manifested gut microbiota partly contributed to colitis alleviation via SCFAs-miRNA-10a-5p-PI3K axis.