Neuronal detection triggers systemic digestive shutdown in response to adverse food sources in Caenorhabditis elegans.

The ability to sense and adapt to adverse food conditions is essential for survival across species, but the detailed mechanisms of neuron-digestive crosstalk in food sensing and adaptation remain poorly understood. Here, we identify a novel mechanism by which Caenorhabditis elegans detect unfavorable food sources through neurons and initiate a systemic response to shut down digestion, thus safeguarding against potential harm. Specifically, we demonstrate that NSY-1, expressed in AWC neurons, detects Staphylococcus saprophyticus (SS) as an unfavorable food source, prompting the animal to avoid and halt digestion of SS. Upon detection, the animals activate the AWC^OFF neural circuit, leading to a systemic digestive shutdown, which is mediated by NSY-1-dependent STR-130. Additionally, NSY-1 mutation triggers the production of insulin peptides, including INS-23, which interact with the DAF-2 receptor to modulate SS digestion and affect the expression of intestinal BCF-1. These findings uncover a crucial survival strategy through neuron-digestive crosstalk, where the NSY-1 pathway in AWC neurons orchestrates food evaluation and initiates digestive shutdown to adapt effectively to harmful food sources.