Early-life exposure to low-dose organophosphorus pesticide (OPP) mixtures and their impact on neonatal neurodevelopment remain insufficiently characterized. In this study, plasma samples from 281 newborns were analyzed for 21 OPPs, and neurodevelopment was assessed using the Neonatal Behavioral Neurological Assessment (NBNA). Mixture models consistently identified fenamiphos and fenitrothion as major contributors to lower NBNA scores. To explore potential underlying mechanisms, network toxicology and infant fecal 16S rRNA sequencing were employed. Higher OPP exposure risk scores were associated with altered gut microbiota, including increased abundance of opportunistic genera such as Acinetobacter and Ralstonia, and decreased levels of beneficial taxa including Lactiplantibacillus. Predicted functional profiling revealed enrichment of microbial pathways related to secretion systems and tryptophan metabolism, which correlated with poorer neurodevelopment. Furthermore, a random forest model integrating microbial functional features showed modestly improved prediction of motor outcomes at age 5, assessed via the Ages and Stages Questionnaires (ASQ), compared with models based on conventional clinical indicators alone. These findings suggest that early-life exposure to OPP mixtures is linked to impaired neonatal neurodevelopment, potentially linked to gut microbiota dysregulation and predicted functional alterations. Importantly, microbial functional signatures may have potential as early-life predictive markers for later motor deficits, highlighting the critical interplay between environmental exposures and the gut-brain axis in shaping neurodevelopmental outcomes. These findings highlight the importance of reducing early-life pesticide exposure and support further research into microbiota-related pathways that may inform strategies to mitigate long-term neurodevelopmental risks.
M. Deng, Jun Qiu, Shi-ting Xiang et al.· Environmental Pollution· 0 citations
BACKGROUND
Although fine particulate matter (PM2.5) has been associated with cognitive dysfunction (CD), the roles of specific PM2.5 components and potential mechanisms remain limited. This study aimed to examine the association of long-term PM2.5 and its components with CD, identify the relative importance of components in the mixture, and generate hypotheses regarding possible biological pathways.
METHODS
A total of 14,379 participants aged ≥ 60 from the Henan Rural Cohort were recruited. CD was assessed using the Mini-Mental State Examination (MMSE) and the Hasegawa Dementia Scale (HDS). Concentrations of PM2.5, black carbon (BC), organic matter (OM), ammonium (NH4+), sulfate (SO42-), and nitrate (NO3-) were derived from the TAP dataset. Logistic regression and weighted quantile sum (WQS) regression were applied to estimate associations of single pollutants and pollutant mixture with CD. Network toxicology and machine learning analyses were performed to explore biological pathways and prioritize candidate genes.
RESULTS
For each interquartile range (IQR) increase in PM2.5, BC, OM, NH4+, SO42-, and NO3-, the odds of CD increased by 19%-43%. BC consistently ranked as the leading contributor (weights: 86.38% to 54.31%), followed by OM (weights: 7.24% to 34.57%) across the four CD definitions. Network toxicology analysis identified 47 candidate PM2.5-CD genes, and RPL23, RPL36AL, and RPS25 were prioritized as hypothesis-generating candidate genes by the random forest model (RF).
CONCLUSION
Long-term exposure to PM2.5 and its components is associated with higher odds of CD in rural older adults. BC and OM may represent important contributors within the PM2.5 mixture. Ribosomal and mitochondrial pathways may be dysregulated in PM2.5-related neurotoxicity, but candidate genes require further validation.
Huanxiang Zhang, Ziyuan Zhang, Z. Tian et al.· Neurotoxicology· 0 citations
