Research Article

Microbiota-modulated CART+ enteric neurons autonomously regulate blood glucose

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Science  16 Oct 2020:
Vol. 370, Issue 6514, pp. 314-321
DOI: 10.1126/science.abd6176

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Metabolic signals from gut microbes

The gut is a stretchy, glandular, and highly innervated tube packed at its distal end with microorganisms. Disruption of the microbial community can lead to metabolic disorders such as obesity and diabetes. Muller et al. investigated how the microbiota interacts with the enteric nervous system to induce a metabolic outcome. A population of autonomous enteric neurons called CART+ neurons are enriched in the ileum and colon, where most of the microbiota resides. Stimulation or ablation of the CART+ neurons alters blood glucose levels, insulin, and feeding behavior. Furthermore, by manipulating the microbiota, the density of enteric neurons responds plastically in an inducible and reversible manner.

Science, this issue p. 314


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.

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