The Gut Microbiome is Significantly Altered in APP/PS1 Mice Following Air Particulate Matter Exposure

Abstract

The detrimental effects of air pollution extend beyond its pathological cardiovascular and pulmonary consequences. Recent research has implicated exposure of air pollution, specifically air particulate matter (PM2.5, <2.5 μm diameter), in Alzheimer’s disease (AD) development, though the pathogenesis remains unknown. Gut dysbiosis (i.e., alterations of gut microbiota resident bacterial populations) can result from dietary changes, stress, medications, particulate matter exposure, and alcohol or chemical consumption. Unbalanced bacterial populations may resolve themselves, though persistent stressors can induce chronic dysbiosis, which is implicated in the development of inflammatory bowel disease, obesity, diabetes, cancer, and AD. Thus, we hypothesized that PM2.5 contributes to gut dysbiosis and detrimental microbial byproducts that may ultimately accelerate AD progression in a transgenic AD mouse model. We tested our hypothesis by subjecting 3‐month‐old AD transgenic (APP/PS1) and non‐carrier wildtype (WT) male mice to filtered air (FA) or PM2.5 exposure for 5 days/week, 6 hours/day for 3 months (n=9‐12). The average daily PM exposure is 90.0 μg/m3, which is a 5‐fold concentration above the ambient mean daily PM2.5 concentration (18.8 ±11.4 μg/m3) at the study site in Columbus, OH. The composition has been previously examined and was found to contain high levels of zinc and iron. Following the 3‐month exposure, fecal samples were collected, and DNA was isolated before 16S Illumina sequencing was performed. Sequencing was implemented to determine gut microbial changes associated with genotype and exposure conditions. This data revealed significant alterations in beta diversity based on genotype and exposure, representing altered bacterial communities associated with experimental conditions (Analysis of Molecular Variance (AMOVA), p<0.001)). Additionally, PM2.5 exposure increased gut microbial alpha diversity for both APP/PS1 and WT mice (Shannon‐Weiner diversity, p<0.05). Taken together, these findings indicate that airborne particulate matter exposure induces gut microbiota changes and contributes to microbial dysfunction in a transgenic mouse model of AD.