School of Public Health, Guangxi Medical University, Nanning, Guangxi 530021, China.
The Eighth People's Hospital of Nanning, Nanning, Guangxi 530001, China.
Ecotoxicol Environ Saf. 2024 Apr 15;275:116257. doi: 10.1016/j.ecoenv.2024.116257. Epub 2024 Apr 1.
Growing evidence has revealed the impacts of exposure to fine particulate matter (PM) and dysbiosis of gut microbiota on neuropsychiatric disorders, but the causal inference remains controversial due to residual confounders in observational studies.
This study aimed to examine the causal effects of exposure to PM 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 PM, PM, PM, and NO; (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 NO, PM, and PM. We also examined the mediation effects of gut microbiota in the associations between PM exposure levels and neuropsychiatric disorders, using two-step MR analyses.
Each 1 standard deviation (1.06 ug/m) increment in PM 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 PM, while non-significant after adjusting for NO and PM. The effects of PM exposure on ADHD and schizophrenia were partially mediated by Lachnospiraceae and Barnesiella, with the proportions ranging from 8.31% to 15.77%.
This study suggested that exposure to PM 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.
越来越多的证据表明，细颗粒物（PM）暴露和肠道微生物群落失调会对神经精神疾病产生影响，但由于观察性研究中存在残留混杂因素，因果关系仍存在争议。
本研究旨在检验 PM 暴露对 4 种主要神经精神疾病（自闭症谱系障碍[ASD]病例数=18381 例，注意缺陷多动障碍[ADHD]病例数=38691 例，精神分裂症病例数=67390 例，阿尔茨海默病[AD]病例数=21982 例）的因果影响，以及肠道微生物群的中介途径。采用两样本孟德尔随机化（MR）分析，其中遗传工具来自全基因组关联研究（GWAS）。纳入的 GWAS 来自：（1）MRC 综合流行病学单位（MRC-IEU）的 PM、PM、PM 和 NO；（2）精神疾病基因组学联盟（PGC）的 ASD、ADHD 和精神分裂症；（3）MRC-IEU 的 AD；和（4）MiBioGen 的肠道微生物群。多变量 MR 分析用于调整 NO、PM 和 PM 的暴露。我们还使用两步 MR 分析，检验 PM 暴露水平与神经精神疾病之间关联的肠道微生物群的中介作用。
PM 浓度每增加 1 个标准差（1.06μg/m），与 ASD（优势比[OR]1.42，95%置信区间[CI]1.00-2.02）、ADHD（1.51，1.15-1.98）、精神分裂症（1.47，1.15-1.87）和 AD（1.57，1.16-2.12）的风险升高相关。对于所有 4 种神经发育障碍，在各种敏感性分析下结果均稳健，而 MR-Egger 方法得出的结果无统计学意义。在调整 PM 后，所有 4 种神经精神疾病的关联仍然显著，而在调整 NO 和 PM 后则不显著。PM 暴露对 ADHD 和精神分裂症的影响部分由 Lachnospiraceae 和 Barnesiella 介导，其比例范围为 8.31%-15.77%。
本研究表明，PM 暴露会增加神经精神疾病的风险，部分原因是影响了肠道微生物群的特征。需要对空气污染物进行综合监管，以帮助预防神经精神疾病。
