Microbiota-modulated CART + enteric neurons autonomously regulate blood glucose

The gut microbiota affects tissue physiology, metabolism, and functionof both the immune and nervous systems. We found that intrinsicenteric-associated neurons (iEANs) in mice are functionally adapted to theintestinal segment they occupy; ileal and colonic neurons are moreresponsive to microbial colonization than duodenal neurons. Specifically, amicrobially responsive subset of viscerofugal CART + neurons, enriched in the ileum and colon, modulated feeding and glucosemetabolism. These CART + neurons send axons to theprevertebral ganglia and are polysynaptically connected to the liver andpancreas. Microbiota depletion led to NLRP6- and caspase 11–dependent lossof CART + neurons and impaired glucose regulation.Hence, iEAN subsets appear to be capable of regulating blood glucose levelsindependently from the central nervous system.