Recent studies have suggested that factors that lead to disruption of gut bacteria might play a critical role in triggering Parkinson’s disease (PD)1. Antibiotic exposure is a key source of disruption of gut bacteria. We propose a robust epidemiologic study to examine the potential association between antibiotic exposure and PD risk. Given that there are no therapies for PD that slow down disease progression, it is critical to identify factors that increase the risk of developing the disease. The primary objective of this study is to determine whether use of specific oral antibiotics increases the risk of PD. Based on prior data,2 we hypothesize that exposure to one or more courses of antianaerobics and tetracyclines (specific classes of antibiotics) is associated with an increased risk of PD. These factors include co-existing conditions, smoking, coffee consumption, healthcare usage, and the specific indication for antibiotic use. If antibiotics are identified as a risk factor for PD, future research can focus on methods to modify the use and impact of antibiotics with the goal of reducing how PD prevalence and reducing complications associated with the disease. If no association is detected, this study will provide important reassurance regarding antibiotic use and PD risk.
Studies have posited that exogenous factors such as antibiotics, that lead to disruption of the intestinal microbiome (dysbiosis), might play a critical role in triggering Parkinson’s disease (PD). A recent study in Finland by Mertsalmi et al. (2019) suggested that healthy individuals who received one or more courses of antibiotics had an increased risk of PD approximately 10-15 years after exposure.
We propose a case-control study using CPRD to examine the potential association between antibiotic exposure and PD risk. Unlike the study from Finland, we will: (1) adjust for smoking, an important confounder for PD risk, (2) study a more diverse population than that of Finland, (3) and examine the indications for antibiotic use, since different types of infections (e.g., GI vs. respiratory) may themselves trigger PD to varying degrees.
The outcome of interest is the odds ratio (OR) of antibiotic exposure (according to class of antibiotics) and risk of PD.
We will select all patients who were discharged from 1994 to 2019 with a diagnosis of PD. For each PD patient, 10 control subjects of the same age (+/-1 year) and sex, living in a similar practice region, and IMD quantile, will be selected. For controls, data will also be acquired for the year 2020 to exclude subjects who already suffered from early PD in 2019 but who were only diagnosed in 2020.
The odds ratio (OR) and 95% confidence intervals (CI) will be estimated for the association between PD and number of antibiotic courses by conditional logistic regression. Then, a multivariate logistic regression will be used to adjust for potential confounders.
Parkinson’s disease diagnosis
Gian Pal - Chief Investigator - Rutgers, The State University of New Jersey
Gian Pal - Corresponding Applicant - Rutgers, The State University of New Jersey
Abner Nyandege - Collaborator - Rutgers, The State University of New Jersey
Daniel Horton - Collaborator - Rutgers Robert Wood Johnson Medical School
Jason Roy - Collaborator - Rutgers, The State University of New Jersey
M. Maral Mouradian - Collaborator - Rutgers Robert Wood Johnson Medical School
Tobias Gerhard - Collaborator - Rutgers, The State University of New Jersey
Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation