Fecal miR-142a-3p from dextran sulfate sodium-challenge recovered mice prevents colitis by promoting the growth of Lactobacillus reuteri.

Feces are enriched with microRNAs (miRNAs) that shape the gut microbiota. These miRNAs are differentially expressed in the feces of healthy and diseased subjects. However, whether fecal miRNAs in subjects with inflammatory bowel diseases are involved in regulating microbiota composition and whether they have any beneficial effects remains unknown. Here, we studied the fecal microbiome composition and miRNA abundance in mice with dextran sulfate sodium (DSS)-induced colitis and mice at the recovery phase to explore different miRNAs expressed, their relations with microbial abundance, and their effects on colitis. We found that miR-142a-3p expression was significantly increased in the feces of mice recovered from colitis and that it could alleviate disease symptoms in mice treated with DSS in a microbiome-dependent manner. Specifically, miR-142a-3p promoted the growth of Lactobacillus reuteri, which had a high abundance in the feces of mice recovered from colitis, by regulating transcripts of polA and locus tag LREU_RS03575. Moreover, L. reuteri, as well as its metabolite reuterin, could alleviate DSS-induced disease symptoms. These results highlight the role of fecal miR-142a-3p in the prevention of colitis. We propose that the feces of subjects who have recovered from diseases might be enriched with miRNAs with preventive effects against those diseases.