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 AWCOFF 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.
Keywords: AWC neuron; C. elegans; NSY-1; awc neuron; developmental biology; digestion; food behavior; neuroscience; nsy-1.
Eating is essential for survival – but not all food is safe. Spoiled or toxic meals can cause illness, so animals must distinguish good food from harmful food. While the brain helps animals smell and taste, it is less clear how the nervous system communicates with the digestive system to prevent harm. The tiny worm Caenorhabditis elegans (C. elegans) is a powerful model organism in biology because it has a simple nervous system and a transparent body. Living in soil and feeding on bacteria, the worm encounters both harmless and harmful species. One such bacterium, Staphylococcus saprophyticus, is toxic to C. elegans. Previous work showed that worms can avoid poor-quality food, but the mechanisms behind this behavior were unknown. Liu et al. investigated how C. elegans detects and responds to dangerous food by exposing the worms to S. Saprophyticus for one to four days and by using a combination of genetic and imaging approaches to study the activity of neurons. With this approach, the team identified a pair of neurons in the worm’s head, called AWC neurons, as key “taste sentinels.” A protein located in these neurons, NSY-1, enabled the worms to recognize S. saprophyticus as a threat. This detection triggered a neural circuit (the AWCOFF state), sending a body-wide signal that shut down the digestive system. Without this protective mechanism governed by the nsy-1 gene, worms continued to digest the toxic bacteria and had a shortened lifespan. Further experiments revealed that these neural signals also regulated hormone-like peptides and gut-specific genes, fine-tuning digestive activity. Thus, NSY-1 functions as a molecular sensor that links the nervous system to the gut, forming a direct communication line that helps the animal avoid harm. These findings reveal a fundamental survival mechanism that may represent an ancient system shared across animals, including humans. Understanding this brain–gut crosstalk in worms could provide insights into how the human nervous system defends against foodborne pathogens and toxins and may also illuminate the biological basis of some digestive disorders. However, further research is needed to determine whether similar signaling pathways exist in mammals. Identifying equivalent molecules in humans could open new avenues for understanding and treating digestive disorders and food-related illnesses.
© 2025, Liu, Tian et al.