Early-life taurine supplementation confers long-term neuroprotection via NF-κB/FOXO-related nutritional programming

Taurine, an important nutritional fortifier in infant formula, is closely associated with neurodevelopment and immune homeostasis. However, existing studies have mainly focused on its immediate promoting effects on neurodevelopment, while whether early-life taurine supplementation confers long-term neuroprotective effects during later developmental stages remains unclear. In this study, a three-stage zebrafish model was established, including early-life taurine supplementation, cessation of supplementation, and subsequent exposure to acrylamide during later development, to evaluate the long-term neuroprotective potential of taurine. The results showed that early-life taurine supplementation significantly alleviated neurobehavioral deficits, oxidative damage in brain tissue, and inflammatory responses induced by acrylamide exposure during later developmental stages. Mechanistically, taurine may exert these effects through coordinated regulation of neuroimmune and metabolic pathways. At the immune level, taurine inhibited NF-κB-related inflammatory activation, suppressed M1-associated microglial markers, and promoted M2-associated responses, thereby improving the neuroimmune microenvironment. At the metabolic level, taurine regulated FOXO pathway-related gene expression and improved glycolysis-related metabolic disturbance, which was associated with reduced oxidative damage and improved energy homeostasis. Overall, these findings suggest that transient taurine supplementation during early life may reduce later susceptibility to foodborne neurotoxicant exposure, which is associated with nutritional programming-like changes in neuroimmune and metabolic pathways. This study provides a new perspective for early-life nutritional intervention and dietary risk assessment.