Abstract
The environment dominates over host genetics in shaping the gut microbiome, which plays a pivotal role in modulating human health. Experimental evidence supports the notion that exposure to pesticides could perturb the gut microbiome, and the toxicant-induced dysbiosis may affect host homeostasis. However, the field of human studies, especially in early life, is still in its infancy. We aimed to evaluate the effects of landscape pesticide exposure on the maternal gut microbiome. Here, we assessed the blood levels of a broad array of pesticides in 405 pregnant women. Gut microbial compositions and functional profiles were assessed by using both 16S rRNA gene amplicon sequencing and shotgun metagenomic sequencing. Microbial alpha diversity indices were regressed on host and environmental factors using linear models. Differences in overall microbial compositions were evaluated by using univariable permutational multivariate analyses of variance (PERMANOVA) with Bray-Curtis dissimilarities. All pesticides, as well as other host and environmental factors, were correlated to the gut microbiome at the phylum, genus, species, and pathway levels employing the multivariable regression models adjusted for the potential covariates, respectively. The joint effects of the mixture of pesticide exposure on the gut microbiome were investigated using quantile g-computation. Microbial ecological networks were constructed via Spearman correlations to explore species co-occurrence patterns related to pesticide exposure. Significant associations were observed between exposure to various pesticides individually or as a mixture and maternal gut microbiome features. Specific taxa and pathways were enriched or depleted in response to varying pesticide concentrations, indicating the potential exposure-response relationships. Notably, mirex exposure showed a positive correlation with both the relative abundance of Blautia_wexlerae and the sucrose biosynthesis II pathway. Microbial co-occurrence network analyses revealed marked shifts in species interactions associated with increasing levels of pesticide exposure. Mediation analyses further identified a greater number of microbial taxa, particularly Blautia_wexlerae, as significant mediators linking pesticide exposure to alterations in microbial functional pathways. Our large-scale amplicon and metagenomic analyses unraveled the extensive impacts of landscape-level pesticides on the maternal gut microbiome. Further observational and experimental research is warranted to validate our findings as well as to elucidate whether and how these microbial changes affect maternal and offspring health.