MicroRNAs and the regulation of intestinal homeostasis

Marah C. Runtsch, June L. Round, Ryan M. O’Connell

The mammalian intestinal tract is a unique site in which a large portion of our immune system and the 10(14) commensal organisms that make up the microbiota reside in intimate contact with each other. Despite the potential for inflammatory immune responses, this complex interface contains host immune cells and epithelial cells interacting with the microbiota in a manner that promotes symbiosis. Due to the complexity of the cell types and microorganisms involved, this process requires elaborate regulatory mechanisms to ensure mutualism and prevent disease. While many studies have described critical roles for protein regulators of intestinal homeostasis, recent reports indicate that non-coding RNAs are also major contributors to optimal host-commensal interactions. In particular, there is emerging evidence that microRNAs (miRNAs) have evolved to fine tune host gene expression networks and signaling pathways that modulate cellular physiology in the intestinal tract. Here, we review our present knowledge of the influence miRNAs have on both immune and epithelial cell biology in the mammalian intestines and the impact this has on the microbiota. We also discuss a need for further studies to decipher the functions of specific miRNAs within the gut to better understand cellular mechanisms that promote intestinal homeostasis and to identify potential molecular targets underlying diseases such as inflammatory bowel disease and colorectal cancer.