Enteroendocrine cells sense bacterial tryptophan catabolites to activate enteric and vagal neuronal pathways.

A gut reaction to microbial metabolites

30 September 2021

Metabolites produced by gut bacteria can activate nerves that connect the intestines to the brain, a finding that could lead to new treatments for gut microbe-related neurological disorders.

Specialized cells that line the intestines sense nutritional and microbial stimuli. But it was unclear whether these biosensor cells, after detecting microbial cues, then relay those signals to the nervous system.

Working with zebrafish, a team that included scientists from Flinders University found that short, rod-shaped bacteria can indeed trigger nerves in the gut through the production of an amino-acid derivative.

This metabolic by-product engages a receptor on intestinal biosensor cells, leading directly to the stimulation of vagal nerve pathways (that affect brain function) and indirectly to the activation of cholinergic neurons (that affect gut motility) through the secretion of a neurotransmitter hormone.

The metabolite, the researchers showed, can also stimulate the same receptor in human and mouse cells.

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References

1. Cell Host & Microbe 29, 1–18 (2021). doi: 10.1016/j.chom.2020.11.011