Certain Antibiotics Increase the Risk of Parkinson Disease

New data could shed some light on the link between antibiotic exposure and Parkinson disease.

A team led by Tuomas Mertsalmi, MD, Department of Neurology, Helsinki University Hospital and Department of Clinical Neurosciences, University of Helsinki, evaluated the impact of antibiotic exposure on the risk of Parkinson disease in a nationwide, register-based, case-control study.

The study included 13,976 patients, as well as 40,697 control patients.

Gut microbiota alterations has been found in prodromal and established Parkinson disease and antibiotic exposure could have long-term effects on the composition of human intestinal microbiota. However, investigators have yet to extensively study the potential connection between antibiotic exposure and the risk of Parkinson disease.

The investigators identified all patients diagnosed with Parkinson disease in Finland between 1998-2014 and obtained data on individual purchases of orally administered antibiotics between 1993-2014.

They then assessed the association between previous antibiotic exposure and Parkinson disease using conditional logistic regression.

The strongest connection with disease risk was observed in oral exposure to macrolides and lincosamides (OR, 1.416; 95% CI, 1.053—1.904).

After they corrected for multiple comparisons, they found that exposure to antianaerobics and tetracyclines 10-15 years before the index date. They also found sulfonamides and trimethoprim 1-5 years before the index date and antifungal medications 1-5 years before the index date were positively associated with Parkinson disease risk.

In a post hoc analysis, the team found that further positive associations were discovered for broad-spectrum antibiotics.

“Exposure to certain types of oral antibiotics seems to be associated with an elevated risk of [Parkinson disease] with a delay that is consistent with the proposed duration of a prodromal period,” the authors wrote. “The pattern of associations supports the hypothesis that effects on gut microbiota could link antibiotics to PD, but further studies are needed to confirm this.”

Earlier this year, investigators found that phosphodiesterase 10A levels, which are associated with motor symptom severity, plummet in middle-stage and advanced patients with Parkinson disease.

The study included 78 patients, 17 of which had been recently diagnosed and were hardly presenting symptoms, while 15 were in early levodopa treatment, 24 had moderate-advanced symptoms addressed with levodopa, and 22 were healthy controls.

All participants underwent phosphodiesterase 10A positron emission tomography, dopamine positron emission tomography, and a 3-Tesla MRI scan.

Overall, the study showed that phosphodiesterase decreases alongside dopamine in PD, and the combination heightens motor symptoms of the disease as it progresses. This potentially opens a new avenue of research—akin to dopamine transporter imagining, but for phosphodiesterase instead—which would allow the disease’s progression to be tracked in greater detail.

In a video interview with MD Magazine®, Sarah Hamm-Alvarez, PhD, emphasized the importance of identifying early signals and/or biomarkers of Parkinson disease, such as the aforementioned loss of phosphodiesterase. The drugs currently used for treating PD are the same drugs used 40 years ago. When trying to develop new, alternative treatments, identifying earlier signs or biomarkers of PD becomes absolutely vital.

“Obviously, any diagnostic biomarker that could provide [diagnosis of] patients at an earlier state would be potentially of great benefit, whether it is a biomarker in bio fluid like tears or saliva or cerebrospinal fluid,” Hamm-Alvarez told MD Mag. “We're very excited about the potential for any biomarker to be able to be paired to new therapies.”

The study, “Antibiotic exposure and risk of Parkinson's disease in Finland: A nationwide case‐control study,” was published online in Movement Disorders.