Editors' ChoiceHost-Microbe Interactions

Micromanaging the microbiome

Sci. Signal.  26 Jan 2016:
Vol. 9, Issue 412, pp. ec16
DOI: 10.1126/scisignal.aaf3005

In addition to acting inside the cells in which they are made, microRNAs (miRNAs) can be released to act at a distance. New research suggests that miRNAs should be added to the growing list of factors—along with diet, the immune system, and host genetics and physiology—that shape the composition of the gut microbiome. Liu et al. found that human and mouse stool samples contained hundreds of miRNAs, some of which were present in both species. Analysis of gut contents from different regions of the mouse intestine showed that the abundance of particular miRNAs varied between different regions of the gut. Furthermore, miRNAs were more abundant in stool samples from germ-free and antibiotic-treated mice than in those from untreated, colonized mice. Microscopic examination of mouse fecal samples revealed the presence of extracellular vesicles, suggesting that these miRNAs may be associated with microvesicles or exosomes. Mice in which the intestinal epithelial cells (IECs) lacked an enzyme required for miRNA processing (Dicer1ΔIEC mice) had altered composition and reduced overall abundance of fecal miRNAs. Knocking out Dicer1 in the lineage of intestinal stem cells that give rise to Paneth and goblet cells also reduced the abundance of fecal miRNAs, but affected a different subset of miRNAs than those affected by knocking out Dicer1 in IECs, implying that these cell types generate different miRNAs. Dextran sulfate sodium (DSS), which damages IECs and goblet cells, also reduced the abundance of fecal miRNAs. The gut microbiomes of Dicer1ΔIEC mice were more diverse than those of wild-type littermates, suggesting that fecal miRNAs regulate the composition of the microbial community. Indeed, oral administration of fecal miRNAs from wild-type mice reduced microbial diversity in the guts of Dicer1ΔIEC mice to more closely resemble that of wild-type mice. Dicer1ΔIEC mice were more susceptible to DSS-induced colitis than were wild-type mice, and fecal miRNAs from wild-type mice reduced the severity of DSS-induced colitis in Dicer1ΔIEC mice. Using in vitro systems, the authors showed that labeled extracellular miRNAs were capable of entering bacteria and that two fecal miRNAs that were predicted to target distinct genes in two different species of gut bacteria affected the abundance of their predicted target mRNAs and stimulated bacterial growth. Thus, miRNAs contribute to regulation of the gut microbiome and may represent a way for manipulating gut microbiome composition in the context of disease.

S. Liu, A, P. da Cunha, R. M. Rezende, R. Cialic, Z. Wei, L. Bry, L. E. Comstock, R. Gandhi, H. L. Weiner, The host shapes the gut microbiota via fecal microRNA. Cell Host Microbe 19, 32–43 (2016). [PubMed]