The Gut and Nonmotor Symptoms in Parkinson's Disease.

Gastrointestinal (GI) symptoms are one of the most common nonmotor symptoms (NMS) in patients with Parkinson's disease (PD) involving the whole GI tract (GIT) and being evident throughout the whole course of the disease. Furthermore, constipation serves as a risk factor for PD as well as an early prodromal NMS of PD. The gut as gateway to the environment with its enteric nervous system (ENS) plays a crucial role in the neurodegenerative process that leads to PD. Alpha-synucleinopathy as the pathological hallmark of PD could be found within the whole GIT in a rostrocaudal gradient interacting with the ENS, the gut microbiome, and enteric glial cells. Bidirectional interactions between the ENS and the central nervous system (CNS) via a brain-gut-enteric microbiota axis have been reported. As well as there is evidence out of animal, autopsy, and epidemiological studies that α-synuclein spreads via rostrocranial transmission by transsynaptic cell-to-cell transfer via the sympathetic and parasympathetic nervous system to the CNS causing the typical neuropathological changes of PD. Recognition of GI NMS as prodromal markers of PD as well as a better understanding of the brain-gut connection offers new insights in the pathophysiology of PD and might provide the opportunity of PD diagnosis before CNS involvement. Hereby the opportunity for development of neuroprotective and disease-modifying therapeutics, respectively, seem to be promising. This chapter covers the variety of GI NMS and its consequences in PD as well as the important role of the gut as part of the pathological process in PD.

Klingelhoefer L ，Reichmann H 《-》

Pathogenesis of Parkinson disease--the gut-brain axis and environmental factors.

Klingelhoefer L ，Reichmann H 《-》

Brain-gut-microbiota axis in Parkinson's disease.

Mulak A ，Bonaz B 《-》

Can the gut be the missing piece in uncovering PD pathogenesis?

It is now well established that Parkinson's disease (PD) is not only a movement disorder of the CNS but also a gastrointestinal disorder affecting the enteric nervous system (ENS). The gut-brain axis is a bidirectional communication between the brain and the gastrointestinal tract, which comprises besides the CNS and the ENS, the intestinal epithelial barrier, the intestinal microbiota and the enteroendocrine systems. In this review, we present the clinical and pathological evidence suggesting that the gut-brain axis is dysfunctional in PD by discussing the possible role of gut microbiota, inflammation and permeability in the development of the disease.

Chapelet G ，Leclair-Visonneau L ，Clairembault T ，Neunlist M ，Derkinderen P ... -  《-》

The gut-brain axis in Parkinson's disease: Possibilities for food-based therapies.

Parkinson's disease (PD) is usually characterized by cardinal motor impairments. However, a range of non-motor symptoms precede the motor-phase and are major determinants for the quality of life. To date, no disease modifying treatment is available for PD patients. The gold standard therapy of levodopa is based on restoring dopaminergic neurotransmission, thereby alleviating motor symptoms, whereas non-motor symptoms remain undertreated. One of the most common non-motor symptoms is gastrointestinal dysfunction usually associated with alpha-synuclein accumulations and low-grade mucosal inflammation in the enteric nervous system. Accumulating evidence suggest that the enteric nervous system is involved in PD pathological progression towards the central nervous system. Moreover, different components of the gut could provide a central role in the gut-brain axis, which is as a bidirectional communicational system between the gastrointestinal tract and central nervous system. Dietary components might influence the gut-brain axis by altering microbiota composition or by affecting neuronal functioning in both the ENS and the CNS. This review gives a comprehensive overview of the evidences supporting the hypothesis that PD could initiate in the gut. We also consider how food-based therapies might then have an impact on PD pathology and/or improve non-motor as well as motor symptoms in PD.

Perez-Pardo P ，Kliest T ，Dodiya HB ，Broersen LM ，Garssen J ，Keshavarzian A ，Kraneveld AD ... -  《-》