Sex differences in the association between long-term ambient particulate air pollution and the intestinal microbiome composition of children

The intestinal microbiome is essential for gastrointestinal and overall health, yet its response to air pollution in children remains underexplored. In a study involving 412 young children from the ENVIRONAGE cohort, stool samples were analysed via Illumina Miseq sequencing to assess microbiome alpha diversity (observed richness, species evenness, and Shannon diversity) and composition. Exposure to previous year particulate air pollution (black carbon, PM_2.5, coarse PM, and PM₁₀) was modeled using high-resolution spatial-temporal interpolation models. Multiple linear regression models were adjusted for a priori selected covariables and stratified by sex. Furthermore, we performed a differential relative abundance analysis at family and genus level, while accounting for the same covariables. Statistically significant effect modification by sex was apparent for several intestinal alpha diversity indices and air pollutants. In boys, we observed negative associations between particulate air pollution exposure and intestinal microbiome richness (estimates ranging from -5.55 to -9.06 per interquartile range (IQR) increase in particulate air pollution exposure) and Shannon diversity (estimates ranging from -0.058 to -0.095 per IQR increase). Differently, in girls non-significant positive associations were observed with species evenness (estimates ranging from 0.019 to 0.020 per IQR increase) and Shannon diversity (estimate 0.065 per IQR increase in black carbon). After multiple testing correction, we reported several bacterial families and genera (Streptococcaceae, Clostridiales Incertae Sedis XIII, Coriobacteriaceae, Streptococcus, and Paraprevotella) to be oppositely associated with particulate air pollution exposure in boys and girls. Our findings show a sex-dependent association between particulate air pollution exposure and intestinal microbiome composition, highlighting boys as potentially more vulnerable to diversity loss associated with childhood exposure to particulate pollution.