Microbiome, Pesticides and Parkinsons in Latinos

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Abstract. This is a supplement to the Microbiome, Pesticides and Parkinson’s (MEP; PI: Dr Ritz) study with the goal to enroll a larger number of highly pesticide-exposed Latino community members. The MEP study hypothesized that a) the human microbiome is affected by chronic environmental exposures, specifically pesticides; and b) an altered gut microbiome composition or function contributes to the progression of neurodegeneration in Parkinson’s disease (PD). PD is a progressive neurodegenerative disease and has important non-motor features including gastro-intestinal (GI) symptoms such as constipation and gastroparesis. The human microbiome has a major role in the uptake and handling of nutrients, medications, and toxins; and affects the immune system. Evidence that the microbiome affects neurologic function, brain activity, and behavior via the ‘gut-brain-axis’ is growing. MEP proposed that pesticides also influence the microbiome and the human immune system in PD. The role of the gut microbiome in PD is underexplored and no study has addressed whether toxins influence neurodegeneration via the microbiome. The MEP study uses a geographic information system (GIS) model-based pesticide exposure model based on records from the California state pesticide use reporting (PUR) system that has been developed in on our previous Parkinson's Disease Susceptibility Genes and Pesticides Study (PEG; R01 ES-010544). Along with the UCLA Division of Digestive Diseases, MEP proposed to analyze the gut microbiome of 400 PD patients and 600 (200 age-matched household & 400 age-sex matched community) controls using 16S ribosomal RNA to assess relative abundance of microbiota with the goal to assess microbiome composition and function in pesticide exposed vs. non-exposed controls and PD patients. In 200 new-onset PD patients, of these 100 medication naïve (MN) PD patients, we collect data on exposures, gut motility indicators, and fecal samples for metabolomics and culture based experiments (before and after starting PD medications); assess differences in relative abundances of microbes over time using 16S ribosomal RNA and shotgun metagenomics and conduct metabolomics (blood or stool) analyses for new onset PD patients (twice, longitudinally) and their household controls. We are now proposing to make a targeted effort to enroll more Latino participants in our study as they are the most highly exposed to pesticides. Latinos live and work in the farming communities of California’s Central Valley and experience unjust disparities in environmental exposures and health care access. It is very important to build trust in these diverse communities to be able to enhance recruitment of Latino participants. Dr. Flores is a member of the Latino community and is familiar with the local health care settings in the central valley. She is uniquely qualified to address the goals of this supplement in order to help increase the participation of Latinos in this important study. She will greatly benefit from working in the well-established research environment of UCLA and will be expanding her expertise to address environmental issues in minority communities in the context of an epidemiologic study while being mentored by experienced researchers in the field. This research is expected to suggest novel prevention options for a growing elderly population with chronic environmental exposures.