Mitigation of maternal fecal microbiota transplantation on neurobehavioral deficits of offspring rats prenatally exposed to arsenic: Role of microbiota-gut-brain axis

It is established that gut microbiota dysbiosis is implicated in arsenic (As)-induced neurotoxic process, however, the underlying mode of action remains largely unclear. Here, through remodeling gut microbiota on As-intoxicated pregnancy rats using fecal microbiota transplantation (FMT) from Control rats, neuronal loss and neurobehavioral deficits in offspring prenatally exposed to As were significantly alleviated after maternal FMT treatment. In prenatal As-challenged offspring after maternal FMT treatment, remarkably, suppressed expression of inflammatory cytokines in tissues (colon, serum, and striatum) were observed along with reversed mRNA and protein expression of tight junction related molecules in intestinal barrier and blood-brain barrier (BBB); Further, expression of serum lipopolysaccharide (LPS), toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (Myd88) and nuclear transcription factor-κB (NF-κB) in colonic and striatal tissues were repressed with activation of astrocytes and microglia inhibited. In particular, tightly correlated and enriched microbiomes were identified such as higher-expressed g_Prevotella, g_UCG_005, and lower-expressed p_Desulfobacterota, g_Eubacterium_xylanophilum_group. Collectively, our results first demonstrated that reconstruction of normal gut microbiota by maternal FMT treatment alleviated prenatal As-induced overall inflammatory state and impairments of intestinal barrier and BBB integrity by impeding LPS-mediated TLR4/Myd88/NF-κB signaling pathway through microbiota-gut-brain axis, which provides a novel therapeutic avenue for developmental arsenic neurotoxicity.