Gut-directed therapy in Parkinson's disease

Abstract

Parkinson's disease (PD) is a common and slow-progressing neurodegenerative disorder characterized by motor and non-motor symptoms, including gastrointestinal (GI) dysfunctions. Over the last years, the microbiota-gut-brain (MGB) axis is emerging as a bacterial-neuro-immune ascending pathway that contributes to the progression of PD. Indeed, PD patients are characterized by changes in gut microbiota composition, alterations of intestinal epithelial barrier (IEB) and enteric neurogenic/inflammatory responses that, besides determining intestinal disturbances, contribute to brain pathology. In this context, despite the causal relationship between gut dysbiosis, impaired MGB axis and PD remains to be elucidated, emerging evidence shows that MGB axis modulation can represent a suitable therapeutical strategy for the treatment of PD. This review provides an overview of the available knowledge about the beneficial effects of gut-directed therapies, including dietary interventions, prebiotics, probiotics, synbiotics and fecal microbiota transplantation (FMT), in both PD patients and animal models. In this context, particular attention has been devoted to the mechanisms by which the modulation of MGB axis could halt or slow down PD pathology and, most importantly, how these approaches can be included in the clinical practice.

Keywords: Parkinson’s disease; enteric inflammation; enteric nervous system; fecal microbiota transplantation; microbiota-gut-brain axis; prebiotics; probiotics.

FIGURE 1

Representative diagram showing MGB signalling, and intestinal and brain alterations associated with PD. In this context, gut-directed therapies (1), through the reshaping of gut microbiota composition and the consequent release of beneficial products, including bacterial metabolites and neurotransmitters (2), besides counteracting enteric inflammation, reinforcing gut barrier integrity, and improving intestinal symptoms (3), exert beneficial effects on CNS alterations. Abbreviations: α-syn: α-synuclein; CNS: central nervous system; GABA: γ-Aminobutyric acid; GI: gastrointestinal; GLP-1: glucagon-like peptide-1; IEB: intestinal epithelial barrier; HPA axis: hypothalamic–pituitary–adrenal axis; MGB: microbiota gut-brain axis; PD: Parkinson’s disease; SCFAs: Short-chain fatty acids.

FIGURE 2

Proposed diagram for the potential application of gut-directed therapies based on PD stages. The present diagram is based on clinical and preclinical studies, so it should always be interpreted in conjunction with patient clinical history, clinical examinations, and PD drugs assumption. For patients in the prodromal stages of PD with intestinal symptoms and gut alterations following endoscopic analysis and subjects with RBD and/or mood disorder, gut-directed therapies, including dietary interventions, prebiotics, and probiotics, can be proposed. For patients in the clinical phase of PD, additional gut directed therapies, including FMT and probiotics, can be added to validated PD drugs. Abbreviations: PD, Parkinson’s disease; RBD, rapid eye movement (REM) sleep behavior disorder.