How pain sensors make the gut weep

Abstract

Nociceptors in the gut are widely known for transmitting pain signals to the spinal cord. Yang et al. now identified a novel microbiome-nociceptor-goblet cell crosstalk that protects the intestinal epithelial barrier by triggering mucus secretion.The intestinal tract is equipped with an epithelial barrier that spatially separates the microbiome and the immune system to avoid unnecessary immune activation. Moreover, the gut epithelium itself is covered by a mucus layer providing a physical barrier to the microbiome. The major building blocks of mucus are MUC2 mucins, which are secreted by the goblet cell. 1 The mechanisms modulating and controlling goblet cell function are however poorly understood. In a recent issue of Cell, Yang et al. elegantly revealed that microbial-mediated activation of Nav1.8 + nociceptors innervating the gut promoted MUC2 mucin secretion by goblet cells via a CGRP-Ramp1 axis during homeostasis and in the context of colitis. 2 Initial evidence indicating a role for host goblet cell-microbiota communication in the maintenance of the mucus layer came from studies in germ-free (GF) mice. Whereas the colonic inner mucus layer of conventionally-raised mice was impenetrable to microorganisms, that of GF mice was more permeable and thinner.