An Intestinal Organ Culture System Uncovers a Role for the Nervous System in Microbe-Immune Crosstalk

Cell. 2017 Mar 9;168(6):1135-1148.e12. doi: 10.1016/j.cell.2017.02.009. Epub 2017 Mar 2.


Investigation of host-environment interactions in the gut would benefit from a culture system that maintained tissue architecture yet allowed tight experimental control. We devised a microfabricated organ culture system that viably preserves the normal multicellular composition of the mouse intestine, with luminal flow to control perturbations (e.g., microbes, drugs). It enables studying short-term responses of diverse gut components (immune, neuronal, etc.). We focused on the early response to bacteria that induce either Th17 or RORg+ T-regulatory (Treg) cells in vivo. Transcriptional responses partially reproduced in vivo signatures, but these microbes elicited diametrically opposite changes in expression of a neuronal-specific gene set, notably nociceptive neuropeptides. We demonstrated activation of sensory neurons by microbes, correlating with RORg+ Treg induction. Colonic RORg+ Treg frequencies increased in mice lacking TAC1 neuropeptide precursor and decreased in capsaicin-diet fed mice. Thus, differential engagement of the enteric nervous system may partake in bifurcating pro- or anti-inflammatory responses to microbes.

Keywords: enteric nervous system; gut microbiota; neuropeptides; regulatory T cells; substance P.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Clostridium / classification
  • Clostridium / growth & development*
  • Clostridium / physiology
  • Intestines / cytology
  • Intestines / growth & development*
  • Intestines / microbiology*
  • Mice
  • Organ Culture Techniques*
  • Symbiosis