Department of Neurosurgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, PR China.
The Institute of Public Administration, Southwest University of Finance and Economics, Chengdu, Sichuan, PR China.
Ecotoxicol Environ Saf. 2024 Oct 15;285:117080. doi: 10.1016/j.ecoenv.2024.117080. Epub 2024 Sep 26.
Epidemiologic investigations have examined the correlation between air pollution and neurologic disorders and neuroanatomic structures. Increasing evidence underscores the profound influence of the gut microbiota on brain health. However, the existing evidence is equivocal, and a causal link remains uncertain. This study aimed: to determine if there is a causal connection between four key air pollutants, and 42 neurologic diseases, and 1325 distinct brain structures; and to explore the potential role of the gut microbiota in mediating these associations.
Univariable Mendelian randomization (UVMR) and multivariable Mendelian randomization (MVMR) models were deployed to estimate the causal impact of air pollutants (including particulate matter [PM] with aerodynamic diameters <2.5 μm [PM2.5], and <10 μm [PM10]; PM2.5 absorbance; and nitrogen oxides [NOx]) on brain health through various Mendelian randomization methodologies. Lastly, the mediating role of the gut microbiome in the connections between the identified pollutants and neurologic diseases and brain structures was systematically examined.
The potential causal associations of PM2.5, PM2.5 absorbance, PM10, and exposure to NOx, with the risks of intracerebral hemorrhage, hippocampal perivascular spaces, large artery strokes, generalized epilepsy with tonic-clonic seizures, Alzheimer's disease, multiple sclerosis, anorexia nervosa, post-traumatic stress disorder (PTSD), and 420 brain structures, were investigated by UVMR analysis. Following adjustment for air pollutants by MVMR analysis, the genetic correlations between PM10 exposure and PTSD and multiple sclerosis remained significant and robust. Importantly, we observed that phylum Lentisphaerae may mediate the association between PM10 and multiple sclerosis. Additionally, PM2.5 absorbance with a greater risk of reduced thickness in the left anterior transverse temporal gyrus of Heschl and a decreased area in the right sulcus intermedius primus of Jensen, mediated by genus Senegalimassilia and genus Lachnospiraceae UCG010, respectively. Finally, we provided evidence that Clostridium innocuum and genus Ruminococcus2 may partly mediate the causal effect of NOx on altered thickness in the left transverse temporal cortex and area in the right sulcus intermedius primus of Jensen, respectively.
This study established a genetic connection between air pollution and brain health, implicating the gut microbiota as a potential mediator in the relationship between air pollution, neurologic disorders, and altered brain structures.
流行病学研究已经考察了空气污染与神经紊乱和神经解剖结构之间的相关性。越来越多的证据强调了肠道微生物群对大脑健康的深远影响。然而，现有证据存在争议，因果关系仍不确定。本研究旨在：确定四种主要空气污染物（包括空气动力学直径小于 2.5μm（PM2.5）和小于 10μm（PM10）的颗粒物、PM2.5 吸光度和氮氧化物）与 42 种神经疾病和 1325 个不同脑结构之间是否存在因果关系；并探讨肠道微生物群在介导这些关联中的潜在作用。
使用单变量孟德尔随机化（UVMR）和多变量孟德尔随机化（MVMR）模型，通过各种孟德尔随机化方法估计空气污染物（包括空气动力学直径小于 2.5μm（PM2.5）和小于 10μm（PM10）的颗粒物、PM2.5 吸光度和氮氧化物）对大脑健康的因果影响。最后，系统地研究了肠道微生物组在确定的污染物与神经疾病和脑结构之间的联系中的中介作用。
通过 UVMR 分析，研究了 PM2.5、PM2.5 吸光度、PM10 和 NOx 暴露与脑出血、海马血管周围空间、大动脉中风、全身性癫痫伴强直-阵挛发作、阿尔茨海默病、多发性硬化症、神经性厌食症、创伤后应激障碍（PTSD）和 420 个脑结构的潜在因果关联。通过 MVMR 分析调整空气污染物后，PM10 暴露与 PTSD 和多发性硬化症之间的遗传相关性仍然显著且稳健。重要的是，我们观察到厚壁菌门 Lentisphaerae 可能介导了 PM10 与多发性硬化症之间的关联。此外，PM2.5 吸光度与左侧额上横回的 Heschel 厚度降低和 Jensen 氏右中间初回面积减小呈正相关，分别由属 Senegalimassilia 和属 Lachnospiraceae UCG010 介导。最后，我们提供了证据表明，Clostridium innocuum 和属 Ruminococcus2 可能部分介导了 NOx 对左侧额上横回厚度和 Jensen 氏右中间初回面积的因果影响。
本研究建立了空气污染与大脑健康之间的遗传联系，表明肠道微生物群可能是空气污染、神经紊乱和改变的大脑结构之间关系的潜在中介。
