Maternal prenatal co-exposure to air pollution and psychological distress shapes the neonatal gut: microbiota-mediated pathways to early neurodevelopment.

Early life gut microbiota function as biological sensors for maternal prenatal exposure and play a crucial role in infant neurodevelopment. During pregnancy, air pollution and psychological distress are regarded as general and specific external exposures, respectively; however, the joint influence of these two domains on shaping early life gut microbiota remains unexplored. In this study, 309 mother-infant pairs were recruited from the obstetrics departments of two tertiary hospitals. We collected data on maternal prenatal air pollution exposure and psychological distress, obtained meconium samples within 48 h after birth, and assessed infant neurodevelopmental outcomes using the Ages and Stages Questionnaire-3 at 1, 3, and 6 months postpartum. Maternal prenatal air pollution-psychological distress exposure patterns were identified using a self-organizing map (SOM). The differential features of the meconium microbiota in relation to co-exposure patterns were assessed using multivariate association of linear models. Finally, the mediating role of the meconium microbiota in co-exposure patterns and infant neurodevelopment was analyzed using mediation analysis. We observed that the meconium microbiota at both the phylum and genus levels differed among the three patterns. Ruminococcus mediated the relationship between co-exposure patterns and infant neurodevelopment at 3 months of age (IE = 0.181-0.261, pFDR < 0.001). These findings support the inclusion of infant gut microbiota within frameworks assessing the risks of maternal prenatal co-exposure to environmental pollution and psychological distress, providing a scientific basis for policymakers to identify intervention targets for high-risk populations.