The gut-brain axis and Parkinson disease: clinical and pathogenetic relevance

Abstract

Gastrointestinal disorders are one of the most significant non-motor problems affecting people with Parkinson disease (PD). Pathogenetically, the gastrointestinal tract has been proposed to be the initial site of pathological changes in PD. Intestinal inflammation and alterations in the gut microbiota may contribute to initiation and progression of pathology in PD. However, the mechanisms underlying this “gut-brain” axis in PD remain unclear. PD patients can display a large variety of gastrointestinal symptoms, leading to reduced quality of life and psychological distress. Gastrointestinal disorders can also limit patients’ response to medications, and consequently negatively impact on neurological outcomes. Despite an increasing research focus, gastrointestinal disorders in PD remain poorly understood and their clinical management often suboptimal. This review summarises our understanding of the relevance of the “gut-brain” axis to the pathogenesis of PD, discusses the impact of gastrointestinal disorders in patients with PD, and provides clinicians with practical guidance to their management.

Cross–trait analysis of Alzheimer’s disease and gastrointestinal tract disorders identifies shared loci highlighting immune-related and statin pathways

“…Taken together, evidence suggests comorbidity between AD and GIT disorders, although it is not clear whether GIT traits are risks for AD or vice versa. Regardless, these findings agree with the concept of the 'gut-brain' axis or the 'gastric mucosa-brain' relationship, which has been implicated in the association between GIT-related traits and central nervous system (CNS) disorders including depression and Parkinson's disease [13][14][15][16] . In support of a possible link between AD and GIT traits, a recent animal model-based study indicates that intragastrointestinal accumulation of Ab may induce gastric function alteration, CNS amyloidosis, and subsequent AD-like dementia 17 .…”

The Prion-Like Spreading of Alpha-Synuclein in Parkinson’s Disease: Update on Models and Hypotheses

“…α-Syn aggregation induced dysfunction in the ENS has, in turn, been implicated in several GIT related non-motor symptoms in PD (i.e., constipation) [ 143 ]. The neuropathological findings that support the role of ‘gut-brain’ axis in PD have recently been discussed in several review opinions [ 144 , 145 , 146 ] and some key aspects of this model are presented below. Within the ENS, α-syn immunopositivity has been reported in the intramuscular myenteric and submucosal Meissner’s plexuses in the gastric, duodenal and colonic biopsies during the prodromal stages of PD (i.e., in the absence of motor disability) [ 18 , 147 , 148 ], as well as in patients with idiopathic rREM sleep behaviour disorder (iRBD), which is present in as much as one-third of PD patients and considered a strong indicator of prodromal PD [ 149 ].…”

“…However, it is worth mentioning that none of the neuropathological studies published to date have identified isolated α-syn accumulation that is localized only to the gut component of ENS and, in the absence of intracerebral LRP, that eventually progressed into clinical PD [ 145 ]. Even if such cases of localized α-syn pathology in ENS do exist, their detection is a highly challenging task technically as the human GIT is 8–10 m long and rigorous analyses would necessitate a large number of tissue sections.…”

Immunoaffinity Capillary Electrophoresis in the Era of Proteoforms, Liquid Biopsy and Preventive Medicine: A Potential Impact in the Diagnosis and Monitoring of Disease Progression

“…For decades, we have known that disease manifests before it is clinically apparent or, in other words, before it manifests with symptoms and signs recognizable to patients and their health providers [9][10][11]. Many chronic diseases are "silent" and may take several years to manifest [12][13][14][15][16][17][18].…”