Recent studies have demonstrated alterations in the gut microbiota composition in mice modeling Alzheimer’s disease (AD) pathologies; however, these studies have only included up to 4 time points. Our study is the first of its kind to characterize the gut microbiota of a transgenic AD mouse model, fortnightly, from 4 weeks of age to 52 weeks of age, to quantify the temporal dynamics in the microbial composition that correlate with the development of disease pathologies and host immune gene expression.

27Background. 28The anterior nares host a complex microbial community that contributes to upper airway health. 29Although the bacterial composition of the nasal passages have been well characterized in 30 healthy and diseased cohorts, the role of prolonged environmental exposures and exercise in 31 shaping the nasal microbiome in healthy adults is poorly understood. In this study, we 32 longitudinally sampled female collegiate Division I athletes from two teams experiencing a 33 similar athletic season and exercise regimen but vastly different environmental exposures 34 (Swim/Dive and Basketball). Using 16S rRNA gene sequencing, we evaluated the longitudinal 35 dynamics of the nasal microbiome pre-, during-, and at the end of the athletic season. 36 Results. 37The nasal microbiota of the Swim/Dive and Basketball teams were distinct from each other at 38 each time point sampled, driven by either low abundance (Jaccard, PERMANOVA p<0.05) or 39 high-abundance changes in composition (Bray-Curtis, PERMANOVA p<0.05). The rate of 40 change of microbial communities were greater in the Swim/Dive team compared to the 41 Basketball team characterized by an increase in Staphylococcus in Swim/Dive and a decrease 42 in Corynebacterium in both teams over time. 43 Conclusions. 44This is the first study that has evaluated the nasal microbiome in athletes. We obtained 45 longitudinal nasal swabs from two gender-matched teams with similar age distributions (18-22 46 years old) over a 6 month period. Differences in the microbiota between teams and over time 47 indicate that chlorine exposure, and potentially athletic training, induced changes in the nasal 48 microbiome. 49 50 51 52

The gut microbiota-brain axis is suspected to contribute to the development of Alzheimer’s Disease (AD), a neurodegenerative disease characterized by amyloid-β plaque deposition, neurofibrillary tangles, and neuroinflammation. To evaluate the role of the gut microbiota-brain axis in AD, we characterized the gut microbiota of 3xTg-AD mice modeling amyloidosis and tauopathy and wild type (WT) genetic controls. Fecal samples were collected fortnightly from 4 to 52 weeks, and the V4 region of the 16S rRNA gene was amplified and sequenced on an Illumina MiSeq. RNA was extracted from the colon and hippocampus, converted to cDNA, and used to measure immune gene expression using RT-qPCR. Diversity metrics were calculated using QIIME 2, and a Random Forest classifier was applied to predict bacterial features that are important in predicting mouse genotype. Gut microbiota were compositionally distinct early in life between 3xTg-AD mice and WT mice (PERMANOVA 8 weeks, p = 0.001, 24 weeks, p = 0.039, and 52 weeks, p = 0.058). We demonstrate that mouse genotype was correctly predicted 90–100% using fecal microbiome composition. Finally, we demonstrate that Bacteroides species relative abundance increased over time in 3xTg-AD mice. Taken together, we demonstrate that changes bacterial gut microbiota composition at pre-pathology timepoints are predictive of development of AD pathologies.