Causal effect of air pollution on the risk of brain health and potential mediation by gut microbiota.

ABSTRACT

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.