Causal effects of PM2.5 exposure on neuropsychiatric disorders and the mediation via gut microbiota: A Mendelian randomization study.

BACKGROUND: Growing evidence has revealed the impacts of exposure to fine particulate matter (PM2.5) and dysbiosis of gut microbiota on neuropsychiatric disorders, but the causal inference remains controversial due to residual confounders in observational studies. METHODS: This study aimed to examine the causal effects of exposure to PM2.5 on 4 major neuropsychiatric disorders (number of cases = 18,381 for autism spectrum disorder [ASD], 38,691 for attention deficit hyperactivity disorder [ADHD], 67,390 for schizophrenia, and 21,982 cases for Alzheimer's disease [AD]), and the mediation pathway through gut microbiota. Two-sample Mendelian randomization (MR) analyses were performed, in which genetic instruments were identified from genome-wide association studies (GWASs). The included GWASs were available from (1) MRC Integrative Epidemiology Unit (MRC-IEU) for PM2.5, PMcoarse, PM10, and NOX; (2) the Psychiatric Genomics Consortium (PGC) for ASD, ADHD, and schizophrenia; (3) MRC-IEU for AD; and (4) MiBioGen for gut microbiota. Multivariable MR analyses were conducted to adjust for exposure to NOX, PMcoarse, and PM10. We also examined the mediation effects of gut microbiota in the associations between PM2.5 exposure levels and neuropsychiatric disorders, using two-step MR analyses. RESULTS: Each 1 standard deviation (1.06 ug/m3) increment in PM2.5 concentrations was associated with elevated risk of ASD (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.00-2.02), ADHD (1.51, 1.15-1.98), schizophrenia (1.47, 1.15-1.87), and AD (1.57, 1.16-2.12). For all the 4 neurodevelopmental disorders, the results were robust under various sensitivity analyses, while the MR-Egger method yielded non-significant outcomes. The associations remained significant for all the 4 neuropsychiatric disorders after adjusting for PMcoarse, while non-significant after adjusting for NOX and PM10. The effects of PM2.5 exposure on ADHD and schizophrenia were partially mediated by Lachnospiraceae and Barnesiella, with the proportions ranging from 8.31% to 15.77%. CONCLUSIONS: This study suggested that exposure to PM2.5 would increase the risk of neuropsychiatric disorders, partially by influencing the profile of gut microbiota. Comprehensive regulations on air pollutants are needed to help prevent neuropsychiatric disorders.

Associations between maternal serum phytoestrogens and liver function markers: a cross-sectional study from China.

Phytoestrogens (PEs) may harm liver function. However, studies in pregnant women are limited. Our study was conducted in pregnant women to assess the effect of serum PEs on liver function markers. We conducted a cross-sectional study focusing in the first trimester of pregnancy. A total of 352 pregnant women were enrolled in the study. We used generalized linear model (GLM) to explore the associations between each PE and each marker of liver function. We used Quantile g-computation (Qgcomp) and Bayesian kernel machine regression (BKMR) models to explore the associations between mixed exposure to all PEs and liver function markers. The GLM results showed that equol (EQU), daidzein (DAD), genistein (GEN), enterolactone (ENT), and enterodiol (END) were negatively correlated with albumin (ALB). DAD and GEN were associated with elevated alanine aminotransferase (ALT). DAD, GEN, naringin (NAR), and glycitein (GLY) were related to elevated aspartate aminotransferase (AST). Mixed exposure model results showed that the mixture of PEs was associated with reduced ALB. Our results support the existence of associations between PEs and maternal liver function in the first trimester. Emphasizing the detrimental associations between serum PEs and liver function in pregnant women is essential to ensure maternal liver health during pregnancy.