The Role of Gut Dysbiosis in Parkinson's Disease

Mechanistic Insights and Therapeutic Options

Qing Wang; Yuqi Luo; K. Ray Chaudhuri; Richard Reynolds; Eng-King Tan; Sven Pettersson

Disclosures

Brain. 2021;144(9):2571-2593. 

In This Article

Abstract and Introduction

Abstract

Parkinson's disease is a common neurodegenerative disorder in which gastrointestinal symptoms may appear prior to motor symptoms. The gut microbiota of patients with Parkinson's disease shows unique changes, which may be used as early biomarkers of disease. Alterations in the gut microbiota composition may be related to the cause or effect of motor or non-motor symptoms, but the specific pathogenic mechanisms are unclear.

The gut microbiota and its metabolites have been suggested to be involved in the pathogenesis of Parkinson's disease by regulating neuroinflammation, barrier function and neurotransmitter activity. There is bidirectional communication between the enteric nervous system and the CNS, and the microbiota-gut-brain axis may provide a pathway for the transmission of α-synuclein.

We highlight recent discoveries about alterations to the gut microbiota in Parkinson's disease and focus on current mechanistic insights into the microbiota-gut-brain axis in disease pathophysiology. Moreover, we discuss the interactions between the production and transmission of α-synuclein and gut inflammation and neuroinflammation. In addition, we draw attention to diet modification, the use of probiotics and prebiotics and faecal microbiota transplantation as potential therapeutic approaches that may lead to a new treatment paradigm for Parkinson's disease.

Introduction

Parkinson's disease is a common neurodegenerative disease largely characterized by the loss of dopaminergic neurons with abnormal accumulation of α-synuclein in the substantia nigra and striatum. The main motor symptoms of Parkinson's disease are tremor, stiffness, bradykinesia and postural instability.[1,2] In addition, non-motor symptoms ranging from sensory abnormalities, behavioural changes, sleep disorders, gastrointestinal and autonomic nervous dysfunction[3–5] may precede the classical motor symptoms.[6] Non-motor symptoms play a dominant role in the clinical manifestations of Parkinson's disease and seriously influence a patient's quality of life.[7,8] More than 80% of patients with Parkinson's disease experience a variety of severe gastrointestinal symptoms such as constipation, nausea and vomiting.[9] The pathogenesis of Parkinson's disease is complex and known to be related to neuroinflammation, oxidative stress and mitochondrial dysfunction.[10–13]

In recent years, the role of the gut microbiota in neurological diseases has attracted considerable interest. The gut microbiota sends signals to the CNS and enteric nervous system through different pathways through metabolites, hormones, the immune system and afferent nerves.[14,15] The enteric nervous system communicates with the CNS through the microbiota-gut-brain axis and a mechanism has been proposed to suggest that gut microbe function participates in the occurrence and progression of the disease. Moreover, the gut microbiota provides a prospective means of treating Parkinson's disease, and research on the Mediterranean diet, probiotics and faecal microbial transplantation shows great application potential. In this review we will: (i) summarize recent studies on the relationship between the gut microbiota and Parkinson's disease; (ii) discuss the possible mechanisms through which the microbiota-gut-brain axis affects the pathogenesis of Parkinson's disease; and (iii) highlight the potential strategies for implementing microbial therapy to treat Parkinson's disease.

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