Perinatal bisphenol A exposure impairs gut microbial colonization: Implications for offspring obesity and neurodevelopment.

Exposure to plasticiser xenobiotics such as BPA has emerged as a significant health challenge due to globalised and industrial packaged food production. Toxicological approaches in animal models have revealed complex effects, using variable doses of BPA, on reproduction, development, obesity, immune function, metabolic and systemic toxicity. Besides, gut microbiota has emerged as a key player in regulating the impact of xenobiotic exposure on host metabolism. The effect that BPA may exert on the gut microbiota and its consequences for the host's health remains unclear. Exposure to BPA during the perinatal period requires special attention and prevention approaches since it is a particularly vulnerable period and highly implicated in the metabolic health of childhood and adulthood. The aim of this study was to assess the effects of the BPA administration during the perinatal period on promoting obesity phenotypes, altering the composition of the gut microbiota and neurocognitive development of the offspring in a murine model. In this study, pregnant mice and their offspring were administered BPA, and the increase in weight and fat accumulation, the gut microbiota composition, and the cognitive development of the offspring were analyzed. In addition, a high-fat diet (HFD) was given to the mice to test for the synergistic obesogenic effect of BPA. Our results demonstrated that BPA exposure impaired the natural remodelling of the gut microbiota during pregnancy. For instance, Akkermansia and Prevotellaceae decreased during natural remodelling of the gut microbiota during pregnancy, but they did not change in the BPA-exposed pregnant mice. Conversely, several members of the Dubosiella genus increased during normal pregnancy but not in BPA-exposed pregnant mice. Moreover, BPA exposure and HFD differentially affect gut microbial transfer from mothers to offspring and both synergistically impact the gut microbiota's establishment in the offspring. Perinatal BPA exposure imprinted changes during colonisation and maturation process of the offspring gut microbiota, identifying Lactobacillus, Eubacterium and Acetatifactor as signature genera enriched in BPA and BPA-exposed mice fed with HFD, taxa involved in a more efficient at energy harvesting from the diet. Moreover, perinatal BPA exposure seemed to alter fat and lean percentages and triggered Muribaculacea taxa imbalance that appears to be associated with disrupted activity, spatial learning, and memory, mimicking impulsivity and hyperactivity-like behavior in the offspring. In conclusion, BPA exposure and HFD exert an influence on the vertical transfer of gut microbiota from mothers to offspring and drive towards an altered establishment of gut microbiota taxa in early life, contributing to enhancing susceptibility to obesity and behavioural disorders.