Mouse and human faeces contains functional microRNAs (miRNAs), according to a new study published in Cell Host & Microbe. The researchers also showed that host faecal miRNA directly regulates microbial gene expression and growth. “It is known that the commensal bacteria in the gut are important in health and disease. However, little is known about how they are naturally regulated, or strategies to manipulate them,” explains first author Shirong Liu. Previous studies have shown that extracellular miRNAs are present in human faeces, leading Liu et al. to investigate whether faecal extracellular miRNAs are functional, and if they can regulate the gut microbiota by altering bacterial gene expression in the gut. The researchers isolated RNA from human and mouse faeces, finding that samples from both species contained specific miRNAs, such as miR-155 and miR-1224.
Bioinformatic analysis predicted that a number of these miRNAs could bind multiple genomic sites in selected bacterial species. The researchers cultured two bacterial species in the presence of synthetic mimetics of identified miRNAs and found that bacterial growth was markedly affected. After showing that fluorescently labelled miRNA was able to enter bacteria, the authors also demonstrated that bacterial gene expression is directly altered when bacteria were cultured with human or mouse faecal miRNAs. Mice lacking the miRNAgenerating protein Dicer only in intestinal epithelial cells had reduced levels of faecal miRNA, suggesting that intestinal epithelial cells are a major source of miRNA in faeces. Faecal miRNA levels were also reduced in mice in which Dicer was knocked out in intestinal goblet cells and Paneth cells.
Further experiments showed that mice with Dicer knocked out specifically in intestinal epithelial cells had dysbiosis, and were more susceptible to induced colitis than wild-type mice. When these knockout mice received faecal miRNA from wild-type mice via gavage before colitis induction, colonic damage was lessened. “Our findings show that the host can actively affect the microbes through miRNAs, and this provides a unique way to manipulate them,” concludes corresponding author Howard Weiner. “We will investigate whether faecal miRNAs are abnormal in disease, and we plan to explore ways to use exogenously administered miRNAs as therapeutic compounds.
ORIGINAL ARTICLE Liu, S. et al. The host shapes the gut microbiota via fecal microRNA. Cell Host Microbe 19, 32–43 (2016)