Probiotic GR-1 supplementation attenuates Pb-induced learning and memory deficits by reshaping the gut microbiota.

Lead (Pb) exposure during early life has been associated with an increased risk of neurodevelopmental disorders, including learning and memory deficits. The intestinal flora, the microbiome-gut-brain axis, could play a significant role in the nervous system. However, the effects of probiotics on ameliorating Pb-induced learning and memory deficits are still unclear. In this study, we showed that adolescent Pb exposure (150 ppm) for 2 months impaired spatial learning and memory ability, accompanied by the decreasing diversity of gut microbiota, and the decreasing abundance of s at the genus level. Surprisingly, administration of the GR-1 (10 organisms/rat/day), not LGG or RC-14, reversed learning and memory deficits induced by Pb exposure. Meanwhile, administration of the GR-1 increased the diversity of the gut microbiota composition and partially normalized the genus level of , , , and in Pb-exposed rats. Notably, supplementation of GR-1 decreased the gut permeability of Pb-exposed rats, reduced proinflammatory cytokines [interleukin-1β (IL-1β) and IL-6] expression, and promoted anti-inflammatory cytokines [granulocyte colony-stimulating factor (G-CSF)] expression. Interestingly, neural cell treatment with G-CSF rescued Pb-induced neurotoxicity. In general, GR-1 supplementation recovered the Pb-induced loss of intestinal bacteria (), which may have reversed the damage to learning and memory ability. Collectively, our findings demonstrate an unexpectedly pivotal role of GR-1 in Pb-induced cognitive deficits and identify a potential probiotic therapy for cognitive dysfunction during early life.