Heat exposure remodels the gut microbiota to promote heat acclimation through a serotonin-mediated gut-brain axis

Rising global temperatures pose an increasing challenge to the survival of endotherms. In this context, heat acclimation is a critical adaptive process that enables long-term survival under warming conditions. However, the mechanisms underlying this adaptive process remain poorly understood in birds, especially heat-sensitive domestic poultry. Here, we investigated how heat acclimation enhances adaptation to high-temperature environments in broiler chickens and examined the role of the gut microbiota in this process. Heat acclimation gradually induced a hypometabolic phenotype in broilers, characterized by reduced thermogenesis and accompanied by remodeling of the gut microbiota. Transplantation of fecal microbiota from heat-adapted donors into recipient broilers remodeled their microbial communities and was associated with reprogramming of tryptophan metabolism, increased hypothalamic serotonin (5-HT) availability, and suppression of endogenous thermogenesis, thereby improving heat tolerance. Notably, both in vitro and in vivo data further showed that 5-HT is associated with upregulation of neuronal transient receptor potential canonical 4 (TRPC4). Intraventricular administration of 5-HT reduced body temperature and thermogenic activity under heat stress, whereas these hypothermic effects were abolished following TRPC4 knockdown. Collectively, our findings demonstrate that heat acclimation promotes metabolic adaptation to warming in birds by remodeling the gut microbiota and regulating the gut-brain axis, providing new insight into microbiota-mediated environmental adaptation in homeotherms.