Interplay between gut bacteria and Parkinson’s disease medication

Sebastiaan P. van Kessel

Research output: ThesisThesis fully internal (DIV)

177 Downloads (Pure)

Abstract

Parkinson’s disease (PD) is a neurodegenerative disorder, which affects approximately 6 million individuals worldwide. The main pathologic feature observed in PD patients is the abnormal aggregation of protein and loss of dopaminergic neurons in the midbrain, resulting in motor deficits.
Levodopa remains the “golden” standard treatment to restore the absence of dopamine in the brain. Although the start of levodopa treatment has an optimal efficacy, the progression of the disease causes a high variability in the efficacy of levodopa treatment among patients resulting in an unstable and unpredictable clinical response; motor-fluctuations. Besides motor deficits, PD patients also experience various non-motor symptoms such as gastrointestinal dysfunction.
In this thesis, we showed that gut bacteria can contribute to the reduction of levodopa availability in the blood-circulation and that they can metabolize the unabsorbed residues of levodopa to various products that alter the gut motility. Furthermore, we showed that the most commonly used PD medications per se may affect the small intestinal motility, the main site of drug absorption, thereby altering the microbiota composition. Such events will potentially create a vicious cycle among the microbiota, PD medication, and gastrointestinal function, and urges for consideration of PD medication and gastrointestinal function when assessing alterations in the PD-associated microbiota. Finally, determining the clinical impact of gut bacteria on PD medication will help reduce the factors contributing to compromised levodopa bioavailability and the unwarranted side effects that result potentially in and from increased treatment regimen.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • University of Groningen
Supervisors/Advisors
  • El Aidy, Sahar, Supervisor
  • Dijkhuizen, Lubbert, Supervisor
Award date5-Nov-2021
Place of Publication[Groningen]
Publisher
DOIs
Publication statusPublished - 2021

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