Prenatal ozone exposure and variations of the gut microbiome: Evidence from a Chinese mother-infant cohort

Background: The gut microbiome is central to human health, but the potential impact of ozone (O3) 3 ) exposure on its establishment in early life has not been thoroughly examined. Therefore, this study aimed to investigate the relationship between prenatal O3 3 exposure and the variations of the human gut microbiome during the first two years of life. Design: A cohort study design was used. Pregnant women in the third trimester were recruited from an obstetric clinic, and long-term follow-ups were conducted after delivery. The gut microbiome was analyzed using the 16 S rRNA V3-V4 gene regions. Functional pathway analyses of gut microbial communities in neonates were performed using Tax4fun. The average concentrations of ambient O3 3 and other air pollutants from pregnancy to delivery were calculated using the China High Air Pollutants (CHAP) dataset, based on the permanent residential addresses of participants. Multiple linear regression and mixed linear models were utilized to investigate the associations between prenatal O3 3 exposure and gut microbiome features. Results: Prenatal O3 3 exposure did not significantly affect the gut microbial alpha diversity of mothers and neonates. However, it was found to be positively associated with the gut microbial alpha diversity in 24-month-old infants. Prenatal O3 3 exposure explained 13.1 % of the variation in neonatal gut microbial composition. After controlling for potential covariates, prenatal O3 3 exposure was associated with neonatal-specific gut microbial taxa and functional pathways. Furthermore, the mixed linear models showed that prenatal O3 3 exposure was negatively associated with variations of Streptococcus (p p-value = 0.001, q-value = 0.005), Enterococcus (p p-value = 0.001, q-value = 0.005), Escherichia-Shigella ( p-value = 0.010, q-value = 0.025), and Bifidobacterium ( p-value = 0.003, q-value = 0.010). Conclusions: This study is the first to examine the effects of prenatal O3 3 exposure on gut microbial homeostasis and variations. It demonstrates that prenatal O3 3 exposure is associated with variations in certain aspects of the gut microbiome. These findings provide novel insights into the dynamics and establishment of the human microbiome during the first two years of life.