Parkinson' disease medication alters rat small intestinal motility and microbiota composition

Abstract

Parkinsons disease (PD) is known to be associated with altered gastrointestinal function and microbiota composition. Altered gastrointestinal function is key in the development of small intestinal bacterial overgrowth, which is a comorbidity often observed in PD patients. Although PD medication could be an important confounder in the reported alterations, its effect per se on the microbiota composition or the gastrointestinal function at the site of drug absorption has not been studied. To this end, healthy (i.e., not PD model) wild-type Groningen rats were employed and treated with dopamine, pramipexole (in combination with levodopa/carbidopa), or ropinirole (in combination with levodopa/carbidopa) for 14 sequential days. Rats treated with dopamine agonists showed a significant reduction in the small intestinal motility and an increase in bacterial overgrowth in the distal small intestine. Importantly, significant alterations in microbial taxa were observed between the treated and vehicle groups, analogous to the changes previously reported in human PD vs HC microbiota studies. These microbial changes included an increase in Lactobacillus and Bifidobacterium, and decrease in Lachnospiraceae and Prevotellaceae. Importantly, certain Lactobacillus species correlated negatively with the plasma levels of levodopa. Overall, the results highlight the significant effect of PD medication per se on the gut microbiota, and the disease-associated comorbidities, including gastrointestinal dysfunction and small intestinal bacterial overgrowth. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSIn the last years many studies focused on the faecal microbiota profiles of Parkinsons disease (PD) patients and compared them to healthy control (HC) subjects and reported a difference between the microbiota profiles. Although some bacterial taxa have been reported to be differential abundant across studies there is a low consensus between the overall changes observed. It remains to be elucidated whether and how the disease status itself, the PD medication or the gastrointestinal dysfunction, an often reported comorbidity, plays a role in the altered microbiota profiles of Parkinsons disease patients. Added value of this studyTwo major confounding factors potentially affecting the microbiota profiles differentiating PD patients from HC subjects are the PD medication and gastrointestinal dysfunction. We showed that PD medication elicits an decreasing effect on the small intestinal gut motility in a healthy (i.e. non Parkinson) rat model which was a contributing factor to the altered microbiota profile observed. We found that taxa reported previously to be differentially abundant were mirrored in our healthy rat model showing the impact of PD medication on microbiota profiles. Implications of all the available evidenceThis study showed that PD medication and gastrointestinal motility are important factors in the microbiota profiles and could explain some of the differential abundant taxa reported in the cross-sectional PD microbiota studies. Future studies should take the potential side effects of medication that could elicit alterations of the microbiota composition into account when seeking for microbial biomarkers of disease status.