Mapping the exposome–microbiota–host axis for prenatal origins of infant health

Prenatal exposures influence infant health, yet the microbiota related mechanisms remain unclear. We profiled 776 maternal exposome variables and meconium microbiota in 1,689 mother–infant pairs, establishing a network linking maternal exposures, neonatal microbiota, and 10 infant outcomes. Using multiomics, pathway enrichment, and robust regression, we identified maternal anthropometrics and clinical indicators as key predictors of infant development, and specific metabolic and chemical exposures as major factors associated with microbiota composition. These microbial changes were associated with infant growth, eczema, and neurodevelopment. Notably, maternal metabolites (e.g., cholesterol) and environmental chemicals (e.g., triphenyl phosphate and perfluorobutane sulfonic acid) were associated with microbiota composition, particularly in Firmicutes, Proteobacteria, and Bacteroidetes. Our findings establish a prenatal exposome–microbiota–host axis, offering a scalable framework to understand early-life health determinants and guide preventive strategies.