Restoration of Gut Microbiota Vertical Transmission by Bifidobacterium Mitigates Pollutant-Induced Intergenerational Obesity

Mass production and widespread distribution of environmental pollutants enhance human susceptibility to disease, which may be related to gut microbial communities. However, the link between the transgenerational toxic effects of environmental pollutants and animal gut microbial communities remains obscure. Here, we show that environmental dose p,p'-DDE (a typical environmental pollutant) exposure prepregnancy reshapes offspring metabolic homeostasis through vertical transmission of the maternal gut microbiota, inducing the development of obesity. In addition, by taking cross-sectional temporal sampling strategy, we show that Bifidobacterium, whose metabolic production of acetate can interfere with obesity by activating Gpr41 and Gpr43, is the key species responsible for this outcome. Supplementation of Bifidobacterium or acetate in dams or offspring reversed the obesity phenotype in offspring mice. Finally, we confirmed the mechanism by which p,p'-DDE induces oxidative stress to inhibit the growth of Bifidobacteriumin vitro, and this phenomenon was found to be mechanically applicable to a wider range of organochlorine pesticides. In conclusion, our study shows that p,p'-DDE can reshape offspring metabolic phenotype through selective vertical transmission of maternal gut microbiota, and maternal or offspring supplementation with Bifidobacterium may be a promising intervention.