Microbiota-modulated CART + enteric neurons autonomously regulate blood glucose

Science. 2020 Oct 16;370(6514):314-321. doi: 10.1126/science.abd6176. Epub 2020 Aug 27.

Abstract

The gut microbiota affects tissue physiology, metabolism, and function of both the immune and nervous systems. We found that intrinsic enteric-associated neurons (iEANs) in mice are functionally adapted to the intestinal segment they occupy; ileal and colonic neurons are more responsive to microbial colonization than duodenal neurons. Specifically, a microbially responsive subset of viscerofugal CART+ neurons, enriched in the ileum and colon, modulated feeding and glucose metabolism. These CART+ neurons send axons to the prevertebral ganglia and are polysynaptically connected to the liver and pancreas. Microbiota depletion led to NLRP6- and caspase 11-dependent loss of CART+ neurons and impaired glucose regulation. Hence, iEAN subsets appear to be capable of regulating blood glucose levels independently from the central nervous system.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Blood Glucose*
  • Caspases, Initiator / genetics
  • Caspases, Initiator / physiology
  • Colon / innervation*
  • Ganglia, Sympathetic / physiology*
  • Gastrointestinal Microbiome / drug effects
  • Gastrointestinal Microbiome / physiology*
  • Ileum / innervation*
  • Liver / innervation
  • Mice
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins / analysis
  • Neurons / chemistry
  • Neurons / physiology*
  • Pancreas / innervation
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / physiology

Substances

  • Anti-Bacterial Agents
  • Blood Glucose
  • Nerve Tissue Proteins
  • Nod-like receptor pyrin domain-containing protein 6, mouse
  • Receptors, Cell Surface
  • cocaine- and amphetamine-regulated transcript protein
  • Casp4 protein, mouse
  • Caspases, Initiator