Gastrointestinal dysfunction in Parkinson's disease

Abstract

Our understanding of dysfunction of the gastrointestinal system in patients with Parkinson's disease has increased substantially in the past decade. The entire gastrointestinal tract is affected in these patients, causing complications that range from oral issues, including drooling and swallowing problems, to delays in gastric emptying and constipation. Additionally, small intestinal bacterial overgrowth and Helicobacter pylori infection affect motor fluctuations by interfering with the absorption of antiparkinsonian drugs. The multifaceted role of the gastrointestinal system in Parkinson's disease necessitates a specific and detailed assessment and treatment plan. The presence of pervasive α-synuclein deposition in the gastrointestinal tract strongly implicates this system in the pathogenesis of Parkinson's disease. Future studies elucidating the role of the gastrointestinal tract in the pathological progression of Parkinson's disease might hold potential for early disease detection and development of neuroprotective approaches.

Unmet needs in Parkinson's disease: New horizons in a changing landscape

“…For example, widespread involvement of the GI system is common in PD, with alpha synuclein and Lewy bodies demonstrated throughout the enteric nervous system, including within myenteric neurons [53] ( Table 2). Indeed, it is now estimated that >70% PD patients have GI disorders, including gastric dysmotility (gastroparesis) and bacterial overgrowth [54]. Very importantly, these GI problems can occur early on in the course of PD, and should no longer be considered a feature of advanced disease [54,55].…”

“…Indeed, it is now estimated that >70% PD patients have GI disorders, including gastric dysmotility (gastroparesis) and bacterial overgrowth [54]. Very importantly, these GI problems can occur early on in the course of PD, and should no longer be considered a feature of advanced disease [54,55]. Since levodopa and many other orally administered PD drugs are absorbed in small intestine, it is thought that these problems might be a key contributor to motor fluctuations in some patients [54].…”

“…Very importantly, these GI problems can occur early on in the course of PD, and should no longer be considered a feature of advanced disease [54,55]. Since levodopa and many other orally administered PD drugs are absorbed in small intestine, it is thought that these problems might be a key contributor to motor fluctuations in some patients [54]. If the drug is not absorbed, it cannot be expected to exert its therapeutic action.…”

Inhibitory system overstimulation plays a role in the pathogenesis of neuromuscular and neurological diseases: a novel hypothesis

“…Administration of benzodiazepines reduces voluntary saccadic eye movement function 42 and increases EEG beta-wave activity 42 , clinical manifestations that also occur in neuromuscular and neurological diseases 18, 43, 44 . Increased GABAergic inhibitory activity can also cause bladder 45, 46 and gastrointestinal dysfunction 47, 48 , both of which can manifest in neuromuscular and neurological diseases 19– 21 . Strikingly, GABAergic activity can also explain the overlapping clinical manifestations between Alzheimer’s disease and alcohol-related dementia 49 , and it can explain the increase in dementia-like symptoms observed after the administration of the benzodiazepine diazepam 50 .…”

Rotenone and elevated extracellular potassium concentration induce cell‐specific fibrillation of α‐synuclein in axons of cholinergic enteric neurons in the guinea‐pig ileum

“…The dominance of non-motor symptoms in the pre-clinical stages of disease has helped guide the quest for biomarkers that can provide an accurate diagnosis before the onset of motor symptoms. For this reason, much attention has been focused on the GI tract, which is heavily burdened by Lewy pathology (13) and commonly expresses symptoms including dysphagia, bloating and constipation (14). Of these, constipation has been reported to manifest as early as 10 years prior to motor symptoms (15).…”