Role of antibiotics and microbiota in parkinson's disease

The aim of this Finnish case-control study was straightforward: to assess the impact of exposure to antibiotics on the risk of developing Parkinson's disease (PD). While it is known that patients with PD show alterations in the gut microbiota and that antibiotic exposure can affect the composition of the microbiota, a potential link between antibiotic exposure and the risk of PD has never been studied.

Case-control study

The team identified all patients diagnosed with PD in Finland between 1998 and 2014 (13,976 individuals) and compared their purchases of oral antibiotics between 1993 and 2014 with those of 40,697 control subjects. The study found correlations between antibiotic use and the risk of PD, the highest being observed for macrolides and lincosamides. These antibiotics are excreted by bile and, therefore, can be found in high concentration in the feces and are responsible for profound and lasting changes in the microbiota: patients who had purchased five of these antibiotics had a 42% increased risk of developing PD within 10 to 15 years, a delay typically observed between the onset of peripheral lesions and the first motor signs. However, in the authors' own opinion, this link remains open to criticism, since it did not stand up to the Benjamini-Hochberg procedure for controlling the rate of false positives (False Discovery Rate or FDR).

Strong correlation for certain antibiotics

On the other hand, even after FDR correction, between one and four antibiotics with anti-anaerobic effects were associated with a 14% increased risk of PD in the 10-15-year period. Based on previous results, this time period may correspond to an alteration of microbiota followed by a cascade of physiological events leading to the first peripheral lesions and diagnosis some years later. Similarly, the use of tetracyclines (10 to 15 years earlier), or sulphonamide and trimethoprim (1 to 5 years earlier) were highly correlated with PD. Lastly, taking antifungal medications also increased the risk of PD, by up to 26% for two purchases in the previous 1 to 5 years. Therefore, the links between antibiotic use and the risk of PD vary according to the class of antibiotics and are stronger for those with anti-anaerobic effects. In addition, a positive correlation was observed between the use of broad-spectrum antibiotics and the risk of PD.

Alteration of the microbiota?

According to the authors, since the gut microbiota is mainly composed of anaerobic bacteria, anti-anaerobic and broad-spectrum antibiotics are those most likely to have a strong impact on its microbial population. This supports the still tentative idea that an alteration of microbiota by antibiotics explains the link between antibiotic usage and risk of PD.