Nutrients activate distinct patterns of small-intestinal enteric neurons
Candice Fung, Tom Venneman, Amy Marie Holland, Tobie Martens, Milvia Alata, Marlene M. Hao, Ceyhun Alar, Yuuki Obata, Jan Tack, Alejandro Sifrim, Vassilis Pachnis, Werend Boesmans, Pieter Vanden Berghe
Abstract
The ability to detect and respond appropriately to ingested nutrients is essential for an organism’s survival and to ensure its metabolic demands are met. Nutrient signals from the gut lumen trigger local intestinal reflexes in the enteric nervous system (ENS) to facilitate digestion and absorption1–4, but the precise cellular pathways that are involved in the initial neuronal sensory process remain unclear. The extent to which the ENS is capable of discerning different luminal chemicals is also unknown. Here we use calcium imaging to identify specific enteric pathways that are activated in response to luminal nutrients applied to mouse jejunum. Notably, we show that different nutrients activate neurochemically defined ensembles of myenteric and submucosal neurons. Furthermore, we find that enteric neurons are not directly sensitive to nutrients but detect different luminal chemicals through the epithelium, mainly via a serotonin signalling pathway. Finally, our data reveal a spatial distribution of luminal information along the radial axis of the intestine, whereby some signals that originate from the villus epithelium are transmitted first to the myenteric plexus, and then back to the submucosal plexus, which is closer to the lumen. Calcium imaging of the mouse jejunum shows that specific nutrients in the intestinal lumen are detected by epithelial cells, which activate specific sets of enteric neurons through a serotonin-mediated signalling process.