The role of the gut in Parkinson's Disease
The gastrointestinal (GI) system features a vital, yet often under-recognised role in management of Parkinson’s disease (PD). GI dysfunctions are prevalent in PD and are some of the most common non-motor symptoms that are evident throughout the entire disease course and involve the whole length of the GI tract, ultimately negatively impacting on patient quality of life and management. Common clinical features of GI dysfunction include abnormal salivation, dysphagia, nausea, vomiting, impaired gastric emptying and constipation and can occur in approximately 80% of PD patients. Many of these GI features can precede the onset of motor symptoms by up to 20 years. Gastroparesis and delayed intestinal absorption negatively impact on treatment, causing erratic levodopa uptake that may lead to motor fluctuations.
The gut has also recently been implicated in the pathogenesis of PD, due to an increased awareness of the gastrointestinal microbiome (GM) and its role in health and disease. Of particular note is an association between the GM and PD and the realisation that the GM can act via a complex bidirectional communication between the gut and the brain, termed the microbiota-gut-brain-axis. Compelling evidence suggests that a shift in GM composition may play an important role in the pathogenesis of PD by facilitating the characteristic ascending neurodegenerative spread of α–synuclein aggregates from the enteric nervous system to the brain, as well as influencing levodopa metabolism. An increasing number of studies evaluating the GM in PD highlight a reduction of short-chain fatty-acid–producing bacteria and oxidative stress as plausible mechanisms that may lead to altered gut permeability, colonic inflammation and α-synuclein aggregation, which may ultimately contribute to the neurogenerative process. Encouragingly, alterations in the GM have repeatedly been observed in PD, supporting a biological link and highlighting it as a potential therapeutic target.