Abstract

Background: The gut-brain axis theory hypothesizes that gut microbiota play a role in the development and progression of Parkinson disease (PD). However, the direction and magnitude of the crosstalk among the gut microbiota, the environment, and PD remain unclear. PD has also been associated with pesticide exposures and certain groups of pesticides may alter gut microbiota. Objective: To compare differences in gut microbiome profiles according to long-term ambient pesticide exposure in elderly not affected by PD. Methods: From 2017 to 2019, we recruited participants free of neurodegenerative diseases from central California. We collected demographic information from structured interviews, and fecal samples from which we sequenced the 16S ribosomal RNA. Incorporating Pesticide Use Reports and Land Use data in California, we employed a geographic information system-based approach to assess exposure to pesticides within a 10-year period before sample collection. We compared the alpha diversity (Observed, Shannon, and Chao1), beta diversity (Unifracs, Bray-Curtis dissimilarity), and taxa abundance in participants exposed to organophosphate (OP) pesticide, antimicrobial and microbial pesticides with unexposed participants. Results: Among the 70 participants, alpha diversity was associated with exposure to microbial pesticides (P(Observed)=0.002, P(Chao1)=0.07, P(Shannon)=0.005) and antimicrobial pesticide (P(Observed)=0.24, P(Chao1)=0.24, P(Shannon)=0.031). After controlling for potential confounders, Bray-Curtis dissimilarity differed between microbial pesticide exposure groups (P=0.007); OP pesticide exposure was associated with a reduction of Actinobacteriota phylum (75% reduction), and exposed also showed differential abundance in 29 genera. Microbial pesticide exposure is associated with a reduction of Cyanobacteria phylum (99% reduction), and exposed also showed differential abundance in 24 genera. Antimicrobial pesticides exposure was associated with differential abundance of 21 genera. Conclusion: Our analyses suggest that long-term ambient pesticide exposure is associated with differences in gut microbial profiles. Our next step will be to explore difference between these controls and PD patients in the context of pesticide exposures. Keywords: Gut microbiome, ambient pesticide exposure, organophosphate pesticide, antimicrobial, microbial

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