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. <i>Ruminococcus</i> mediated the relationship between co-exposure patterns and infant neurodevelopment at 3 months of age (IE = 0.181-0.261, <i>p</i>_FDR < 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.