GUT MICROBIOTA REGULATES EXERCISE-INDUCED HORMETIC MODULATION OF COGNITIVE FUNCTION

Physical exercise exerts a hormetic influence on brain function, whereby moderate levels of training enhance cognition and neurogenesis, while excessive intensity or duration may become detrimental. Yet, the underlying mechanisms of this dose-dependent effect remain unclear. Here, we investigated the contribution of the gut microbiota to exercise-induced brain plasticity. Adult mice underwent a treadmill running protocol (40 min at 1200 cm/min) and were compared to sedentary controls. Moderate exercise improved cognitive performance in object recognition and spatial memory tasks and increased hippocampal neurogenesis, effects that vanished under more intensive or prolonged training. 16S rRNA sequencing revealed distinct microbiota profiles across exercise conditions, with significant shifts in alpha and beta diversity and in the abundance of specific bacterial taxa, including Angelakisella, Acetatifactor, Erysipelatoclostridium, and Coriobacteriaceae UCG-002. Several of these bacterial families correlated with cognitive outcomes. To assess causality, fecal microbiota transplantation (FMT) from exercised to sedentary mice was performed, reproducing the cognitive and neurogenic improvements observed in donors. These findings demonstrate that the beneficial, hormetic effects of exercise on cognition and neurogenesis are mediated by gut microbiota remodeling, uncovering a microbiota-driven mechanism that links physical activity to brain plasticity and cognitive health.