Intestinal microbiome in response to air pollutant exposure in pregestational and gestational murine females and their male and female offspring

We investigated the impact of chronic air pollutant (AP) exposure upon intestinal microbial diversity, composition, and metagenomic inferred functional pathways in murine pregestational and late gestational adult females, and male and female postnatal offspring (P21), compared to age- and sex- matched controls (CON). Intestinal microbiome analysis was undertaken with certain phenotypic characteristics in adult non-pregnant and pregnant females and the male and female offspring. In response to AP, pooled male and female offspring displayed no difference in E19 fetal and P1 postnatal body weights. At P21, females exposed in-utero to AP were heavier with increased fat and muscle mass at one month versus CON. Males were no different at P21 and 1 month revealing decreased fat mass and hyperglycemia. In pregestational/gestational females, AP did not change microbial α- or β-diversity from the respective CON. Gestational females showed AP induced changes in taxonomic composition such as reduced Bacteroides and increased Firmicutes, Verrucomicrobia, and Akkermansia, among others. In response to intra-uterine AP exposure, the offspring intestinal microbiome revealed more compelling differences in α- and β- diversity than adult females. While certain microbial changes were common in both sexes, sex-specific differences also emerged with reduced α-diversity, decreased Bacteroides and increased Akkermansia in males only. The metagenomic inferred pathways revealed perturbations in multiple pathways. We conclude that the offspring exposed in-utero to AP revealed sex-specific changes in microbial diversity, composition and function, displaying certain similarities with distinct differences from mothers. These early life changes were associated with the subsequent emergence of pre-diabetes and adiposity.