Nutrient sensing and small intestinal enteric neurons

Abstract

Different nutrients activate a distinct combination of enteric neurons in the small intestine, according to new research published in Nature. The findings add to our understanding of how the luminal environment in the gut can induce physiological responses.

The researchers used calcium imaging to identify and trace specific pathways of enteric neurons that are activated in response to different luminal nutrients applied to the mouse jejunum. Enteric nervous system activity was recorded in response to mucosal stimuli ex vivo and in vivo in mice. Crucially, different nutrients (glucose, acetate, l-phenylalanine as a model sugar, short-chain fatty acid and amino acid, respectively) activated distinct ensembles of myenteric and submucosal neurons. The nutrients (that is, chemically distinct signals) were detected by epithelial cells, which then, via a serotonin-mediated signalling process, led to enteric neuron activation. Interestingly, there was a spatial distribution of this luminal information relay along the radial axis of the intestine, such that some signals that originated from the intestinal villi are transmitted first to neurons in the outer myenteric plexus and then back to the inner submucosal plexus. Further work is needed to decipher the full extent of neuronal activation to downstream neurons (enteric interneurons and motor neurons) and extrinsic nerves beyond the initial stimulation site.