Parkinson’s disease treatment leaves a mark in the gut

The human gut teems with bacteria that have critical roles in many facets of human health, including food and drug metabolism, mood regulation, and immune system function. Maintenance of these bacteria through diet, avoidance of environmental toxins, and careful use of antibiotics therefore supports not only overall health, but gut health too. Recent studies caution that gut bacteria maintenance may be even more complicated, however, as drugs commonly taken for treating nervous system diseases are disruptive to gut bacteria.

One study demonstrated that the Parkinson’s disease drug entacapone exerts its disruptive effect by depleting iron from bacteria in the gut and consequently slowing bacterial growth. A team of researchers gathered fecal samples from six healthy adults and treated the samples with doses of entacapone similar to what is used in Parkinson’s disease treatment. Using probes that detect ribosomal RNA specific to different bacterial taxa and a technique called stimulated Raman scattering (SRS) microscopy, the team observed that entacapone-treated bacteria across a number of taxa were less metabolically active. They also observed that adding iron to the entacapone treatments reversed the effect of entacapone on metabolic activity. Lastly, the team saw that the entacapone treatments increased the prevalence of bacteria that efficiently acquire iron from the environment and which also tended to carry antibiotic resistance and virulence genes such as E. coli.

Altogether, the study suggests that entacapone disrupts bacterial communities in the gut via iron starvation and, furthermore, selects for pathogenic bacteria that are less susceptible to such iron starvation. The findings prompt questions about whether other nervous system disease treatments disrupt gut bacteria through a similar nutrient starvation mechanism, and about the strategies that can be used to curb this starvation.

This study was led by Fátima Pereira and Xiaowei Ge at University of Vienna and Boston University, respectively.

Managing correspondent: Wilaysha Evans

Press article: https://www.nature.com/articles/s41564-024-01863-y (Nature News & Views)

Journal article: https://www.nature.com/articles/s41564-024-01853-0 (Nature)

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