INVESTIGATING THE GUT–BRAIN INTERACTION IN PARKINSON'S DISEASE: NEUROINFLAMMATION, MICROBIOME DYSBIOSIS, AND THERAPEUTIC INTERVENTIONS

Abstract

An aging population is predicted to increase the global burden of Parkinson's disease (PD), a neurodegenerative disorder that progresses over time and manifests in both motor and non- motor ways. There is mounting evidence that the gut-brain axis (GBA) mediates PD development from sites other than the central nervous system (CNS), including the gastrointestinal tract. This review compiles the most recent findings on the function of gut microbiome dysbiosis in Parkinson's disease, including its impact on neurodegenerative processes related to the immune system, neuroendocrine systems, and metabolism. Patients with PD typically exhibit changes in the composition of their gut microbiome, including elevated pro-inflammatory taxa and decreased numbers of bacteria that produce short-chain fatty acids (SCFAs). These changes are linked with disruption of gut barrier function, intestinal inflammation and disturbance of neurotransmitter metabolism. When looking at it from a scientific perspective, dysbiosis can cause α-synuclein misfolding and propagation, inflammation in the nervous system, and problems with the kynurenine pathway's metabolism of the amino acid tryptophan. Thanks to developments in shotgun metagenomics, which have increased our understanding of disease-associated pathways, high-resolution functional profiling of microbial communities is now feasible. Furthermore, prodromal symptoms, such as REM sleep behavior disorder, were similarly associated with microbiome changes, suggesting a potential for early diagnosis. Competing, though still in their infancy, therapies that target the microbiome include fecal microbiota transplantation, probiotics, and prebiotics. More longitudinal and mechanistic research into the gut microbiome is necessary since it may one day serve as a biomarker for Parkinson disease and a target for treatments.