Candice Fung1, Bert Cools1, Sergio Malagola1, Tobias Martens1, Jan Tack2, Youcef Kazwiny1, Pieter Vanden Berghe1. 1. Laboratory for Enteric NeuroScience (LENS) Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium. 2. Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium.
Abstract
BACKGROUND: Gastrointestinal (GI) function is critically dependent on the control of the enteric nervous system (ENS), which is situated within the gut wall and organized into two ganglionated nerve plexuses: the submucosal and myenteric plexus. The ENS is optimally positioned and together with the intestinal epithelium, is well-equipped to monitor the luminal contents such as microbial metabolites and to coordinate appropriate responses accordingly. Despite the heightened interest in the gut microbiota and its influence on intestinal physiology and pathophysiology, how they interact with the host ENS remains unclear. METHODS: Using full-thickness proximal colon preparations from transgenic Villin-CreERT2;R26R-GCaMP3 and Wnt1-Cre;R26R-GCaMP3 mice, which express a fluorescent Ca2+ indicator in their intestinal epithelium or in their ENS, respectively, we examined the effects of key luminal microbial metabolites (SCFAs and 5-HT) on the mucosa and underlying enteric neurons. KEY RESULTS: We show that the SCFAs acetate, propionate, and butyrate, as well as 5-HT can, to varying extents, acutely elicit epithelial and neuronal Ca2+ responses. Furthermore, SCFAs exert differential effects on submucosal and myenteric neurons. Additionally, we found that submucosal ganglia are predominantly aligned along the striations of the transverse mucosal folds in the proximal colon. CONCLUSIONS & INFERENCES: Taken together, our study demonstrates that different microbial metabolites, including SCFAs and 5-HT, can acutely stimulate Ca2+ signaling in the mucosal epithelium and in enteric neurons.
BACKGROUND: Gastrointestinal (GI) function is critically dependent on the control of the enteric nervous system (ENS), which is situated within the gut wall and organized into two ganglionated nerve plexuses: the submucosal and myenteric plexus. The ENS is optimally positioned and together with the intestinal epithelium, is well-equipped to monitor the luminal contents such as microbial metabolites and to coordinate appropriate responses accordingly. Despite the heightened interest in the gut microbiota and its influence on intestinal physiology and pathophysiology, how they interact with the host ENS remains unclear. METHODS: Using full-thickness proximal colon preparations from transgenic Villin-CreERT2;R26R-GCaMP3 and Wnt1-Cre;R26R-GCaMP3 mice, which express a fluorescent Ca2+ indicator in their intestinal epithelium or in their ENS, respectively, we examined the effects of key luminal microbial metabolites (SCFAs and 5-HT) on the mucosa and underlying enteric neurons. KEY RESULTS: We show that the SCFAs acetate, propionate, and butyrate, as well as 5-HT can, to varying extents, acutely elicit epithelial and neuronal Ca2+ responses. Furthermore, SCFAs exert differential effects on submucosal and myenteric neurons. Additionally, we found that submucosal ganglia are predominantly aligned along the striations of the transverse mucosal folds in the proximal colon. CONCLUSIONS & INFERENCES: Taken together, our study demonstrates that different microbial metabolites, including SCFAs and 5-HT, can acutely stimulate Ca2+ signaling in the mucosal epithelium and in enteric neurons.
Authors: Sarah A Najjar; Brian S Edwards; Kathryn M Albers; Brian M Davis; Kristen M Smith-Edwards Journal: Am J Physiol Gastrointest Liver Physiol Date: 2021-09-01 Impact factor: 4.871