MicroRNA-146a Deficiency Protects against Listeria monocytogenes Infection by Modulating the Gut Microbiota

The gut microbiota and microRNAs play important roles in the defense against infection. However, the role of miR-146a in infection and gut microbiota remains unclear. We tried to determine whether miR-146a controlled infection by regulating the gut microbiota. Wild-type and miR-146a-deficient mice or macrophages were used to characterize the impact of miR-146a on animal survival, cell death, bacterial clearance, and gut microbiota following challenge. We found that infection induced miR-146a expression both in vitro and in vivo. When compared to wild-type mice, miR-146a-deficient mice were more resistant to infection. MiR-146a deficiency in macrophages resulted in reduced invasion and intracellular survival of . High-throughput sequencing of 16S rRNA revealed that the gut microbiota composition differed between miR-146a-deficient and wild-type mice. Relative to wild-type mice, miR-146a-deficient mice had decreased levels of the phylum, family, and genus, and significantly increased short-chain fatty acid producing bacteria, including the genera , , and . Wild-type mice co-housed with miR-146a-deficient mice had increased resistance to , indicating that miR-146a deficiency guides the gut microbiota to alleviate infection. Together, these results suggest that miR-146a deficiency protects against infection by regulating the gut microbiota.