Gut dysfunction in Parkinson's disease

Abstract

Early involvement of gut is observed in Parkinson’s disease (PD) and symptoms such as constipation may precede motor symptoms. α-Synuclein pathology is extensively evident in the gut and appears to follow a rostrocaudal gradient. The gut may act as the starting point of PD pathology with spread toward the central nervous system. This spread of the synuclein pathology raises the possibility of prion-like propagation in PD pathogenesis. Recently, the role of gut microbiota in PD pathogenesis has received attention and some phenotypic correlation has also been shown. The extensive involvement of the gut in PD even in its early stages has led to the evaluation of enteric α-synuclein as a possible biomarker of early PD. The clinical manifestations of gastrointestinal dysfunction in PD include malnutrition, oral and dental disorders, sialorrhea, dysphagia, gastroparesis, constipation, and defecatory dysfunction. These conditions are quite distressing for the patients and require relevant investigations and adequate management. Treatment usually involves both pharmacological and non-pharmacological measures. One important aspect of gut dysfunction is its contribution to the clinical fluctuations in PD. Dysphagia and gastroparesis lead to inadequate absorption of oral anti-PD medications. These lead to response fluctuations, particularly delayed-on and no-on, and there is significant relationship between levodopa pharmacokinetics and gastric emptying in patients with PD. Therefore, in such cases, alternative routes of administration or drug delivery systems may be required.

Keywords: Parkinson’s disease, Gut dysfunction, Sialorrhea, Dysphagia, Gastroparesis, Constipation, Gut microbiota

Core tip: Gut is involved in early Parkinson’s disease (PD) with extensive synuclein pathology, following a rostrocaudal gradient along the gastrointestinal system. It may act as the starting point of PD pathology with prion-like spread toward the central nervous system. The clinical manifestations include malnutrition, oral and dental disorders, sialorrhea, dysphagia, gastroparesis, constipation, and defecatory dysfunction. These are distressing for the patients and need to be managed properly by pharmacological or non-pharmacological measures. Gut dysfunction also leads to response fluctuations in PD and this may require alternative routes of administration or drug delivery systems for anti-PD medications.