Developmental arsenic exposure induces dysbiosis of gut microbiota and disruption of plasma metabolites in mice

Arsenic is a notorious environmental pollutant. Of note, developmental arsenic exposure has been found to in-crease the risk of developing a variety of ailments later in life, but the underlying mechanism is not well un-derstood. Many elements of host health have been connected to the gut microbiota. It is still unclear whether and how developmental arsenic exposure affects the gut microbiota. In the present study, we found that develop-mental arsenic exposure changed intestinal morphology and increased intestinal permeability and inflammation in mouse pups at weaning. These alterations were accompanied by a significant change in gut microbiota, as evidenced by considerably reduced gut microbial richness and diversity. In developmentally arsenic-exposed pups, the relative abundance of Muribaculaceae was significantly decreased, while the relative abundance of Akkermansia and Bacteroides was significantly enhanced at the genus level. Metabolome and pathway enrichment analyses indicated that amino acid and purine metabolism was promoted, while glycerophospholipid metabolism was inhibited. Interestingly, the relative abundance of Muribaculaceae and Akkermansia showed a strong corre-lation with most plasma metabolites significantly altered by developmental arsenic exposure. These data indicate that gut microbiota dysbiosis may be a critical link between developmental arsenic exposure and metabolic disorders and shed light on the mechanisms underlying increased susceptibility to diseases due to developmental arsenic exposure.