Heterozygous disruption of beclin 1 mitigates arsenite-induced neurobehavioral deficits via reshaping gut microbiota-brain axis

摘要

Gut microbiota is intimately involved in numerous aspects of human health. Arsenite expouse can perturb gut microbiota and is linked to increased susceptibility of individual to arsenite-related diseases. However, how microbiome factors influence arsenite-induced neurotoxicity remains largely unknown. In this study, after treating of healthy adult female mice with arsenite via drinking water for 6 months, our results clearly revealed that chronic arsenite exposure not only perturbed the composition of gut microbiota but also caused neurobehavioral dysfunctions, which manifested by learning and memory deficits and anxiety-like behavior. Given that the overactive autophagy directly leads to gut pathological changes, we further assessed whether inhibiton of autophagy by genetic mean could reverse arsenite-induced neurobehavioral dysfunctions. Our results illustrated for the first time that heterozygous disruption of beclin 1, which played a central role in autophagy, alleviated the perturbation of gut microbiome phenotypes induced by arsenite, and ultimately leading to the improvement of neurobehavioral deficits through gut-brain communication. These findings provide a new clue that regulation of autophagy is a potential approach for probing the functional impacts of arsenite on the gut microbiome, and it also may be severed as a way for protection strategies against arsenite neurotoxicity.