Treg/Th Cell Imbalance Is Negatively Associated with Gut Microbiota Dysbiosis and Growth Impairment in Children Exposed to PFAS, PAHs, and Phthalates

Exposure to environmental pollutants such as PFAS, PAHs, and phthalates has been associated with gut dysbiosis and developmental abnormalities in children, yet the underlying immunological mechanisms remain poorly understood. This study investigated whether disruption of the Treg/effector Th cell balance is association with these adverse effects. Our results demonstrated that exposure to specific pollutants, including 2-OHFlu, mBP, miBP, and mEHHP were significantly reduced Treg cell frequency and the Treg/effector T cell ratio. Furthermore, exposure to PFHxS, 3-OHFlu, and mBP was negatively correlated with gut microbiota α-diversity. Additionally, PFHxS, PFNA, 2-OHNap, and mBP were associated with reduced levels of SCFAs, key metabolites that were positively correlated with α-diversity. Notably, our studies showed most SCFAs showed negative correlations with the Treg/Th cell ratio, with valeric acid demonstrating a specific and significant association with Treg/Th17 cell ratio balance. Finally, linear regression confirmed that several pollutants, including PFHxS, mBP, 3-OHFlu, and 2-OHNap, were negatively associated with the Body Mass Index-for-Age Z-score. Collectively, these findings delineate a potential mechanistic pathway whereby PFAS, PAHs, and may impair child growth by reducing gut microbiota diversity, suppressing SCFA production, and disrupting Treg/effector Th cell-mediated intestinal immune tolerance. This study provides the first evidence linking the microbiome-SCFA-immune tolerance axis to pollutant-associated developmental toxicity in children.