Helsinki, Finland—Is more exposure to commonly used oral antibiotics associated with increased risk of Parkinson’s disease (PD)?

That possibility is suggested by a recently published study in the journal Movement Disorders.

Helsinki University–led researchers note that the strongest links were found with broad-spectrum antibiotics and those targeted to anerobic bacteria and fungi.

The timing of antibiotic exposure also seemed to play a role, according to the study team, which asserts that certain antibiotics can predispose to PD with a delay of up to 10 to 15 years, and that the connection might be explained by the drugs’ disruptive effects on the gut microbial ecosystem.

“The link between antibiotic exposure and Parkinson’s disease fits the current view that in a significant proportion of patients, the pathology of Parkinson’s may originate in the gut, possibly related to microbial changes, years before the onset of typical Parkinson motor symptoms such as slowness, muscle stiffness and shaking of the extremities,” explained the research team leader, neurologist Filip Scheperjans MD, PhD, from Helsinki University Hospital. “It was known that the bacterial composition of the intestine in Parkinson’s patients is abnormal, but the cause is unclear. Our results suggest that some commonly used antibiotics, which are known to strongly influence the gut microbiota, could be a predisposing factor.”

The authors write that gut microbiota alterations have been found in prodromal and established PD. They add that antibiotic exposure can have long-term effects on the human intestinal microbiota, yet no previous research has been conducted on the potential connection between antibiotic exposure and PD risk, leading to their study.

Researchers sought to evaluate the impact of antibiotic exposure on the risk of PD in a nationwide, register-based, case-control study. To do that, they identified all patients who were diagnosed with PD in Finland during the years 1998 to 2014.

In addition, information was obtained on individual purchases of orally administered antibiotics during the years 1993 to 2014 and used to assess the association between prior antibiotic exposure and PD. Included in the study population were 13,976 PD cases and 40,697 controls.

Results indicated that the strongest connection with PD risk was found for oral exposure to macrolides and lincosamides (adjusted odds ratio up to 1.416; 95% CI, 1.053-1.904).

After correction for multiple comparisons, the study team found that the following was positively associated with PD risk:
• Exposure to antianarobics and tetracyclines 10 to 15 years before the index date
• Exposure to sulfonamides and trimethoprim 1 to 5 years before the index date 
• Exposure to antifungal medications 1 to 5 years before the index date

Post hoc analyses identified further positive associations for broad-spectrum antibiotics.

“Exposure to certain types of oral antibiotics seems to be associated with an elevated risk of PD with a delay that is consistent with the proposed duration of a prodromal period,” the authors conclude. “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.”

Background information in the articles points out that pathological changes common in PD have been observed up to 20 years before diagnosis. In addition, the authors write that constipation, irritable bowel syndrome, and inflammatory bowel disease have been associated with a higher risk of developing PD.

“Exposure to antibiotics has been shown to cause changes in the gut microbiome and their use is associated with an increased risk of several diseases, such as psychiatric disorders and Crohn’s disease. However, these diseases or increased susceptibility to infection do not explain the now observed relationship between antibiotics and Parkinson’s,” the study notes.

“The discovery may also have implications for antibiotic prescribing practices in the future. In addition to the problem of antibiotic resistance, antimicrobial prescribing should also take into account their potentially long-lasting effects on the gut microbiome and the development of certain diseases,” Dr. Scheperjans adds.

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