1. Microbiota-modulated CART + enteric neurons autonomously regulate blood glucose.
- Author
-
Muller PA, Matheis F, Schneeberger M, Kerner Z, Jové V, and Mucida D
- Subjects
- Animals, Anti-Bacterial Agents pharmacology, Caspases, Initiator genetics, Caspases, Initiator physiology, Gastrointestinal Microbiome drug effects, Liver innervation, Mice, Mice, Inbred C57BL, Nerve Tissue Proteins analysis, Neurons chemistry, Pancreas innervation, Receptors, Cell Surface genetics, Receptors, Cell Surface physiology, Blood Glucose, Colon innervation, Ganglia, Sympathetic physiology, Gastrointestinal Microbiome physiology, Ileum innervation, Neurons physiology
- 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., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)- Published
- 2020
- Full Text
- View/download PDF