A neuroscience perspective of the gut theory of Parkinson's disease

Abstract

Parkinson's disease is caused by complex interactions between environmental factors and a genetic predisposition. Environmental factors include exposure to pesticides and toxins, heavy metals and accumulation of iron and/or manganese in the brain. However, accumulating evidence indicates that gut-brain health and function are impaired in Parkinson's disease, often a decade before motor symptoms are diagnosed. We present the gut-brain theory of Parkinson's disease and summarise the peripheral and central nervous system pathology, gastrointestinal symptoms experienced by many Parkinson's patients, the route by which gut-brain dysfunction may occur and changes in gut microbiota that are associated with disease expression. Finally, we consider future gut-based treatments to prevent or slow down the progression of Parkinson's disease and explore whether this knowledge may highlight biomarkers to be included in complex algorithms in the future to assess a person's risk of developing Parkinson's disease.

Is there a close association of depression with either constipation or dysosmia in Parkinson’s disease?

“…The gastrointestinal spreading of α-syn to brainstem nuclei is possibly the main mechanism by which depression is caused, rather than by the involvement of the limbic system through the olfactory bulbs. Lewy body pathology initially involves the enteric plexus of the gastrointestinal tract and spreads centrally to the DMV, which could cause the prodromal non-motor symptom of constipation in PD patients 3 , 14 – 18 . Afterwards, the DMV is connected to the raphe nuclei and LC.…”

Probable Mechanism of Antiepileptic Effect of the Vagus Nerve Stimulation in the Context of the Recent Results in Sleep Research

“…There is also a growing body of evidence pointing to the link between visceral abnormalities and psychiatric disorders. For example, it was proposed that degeneration of cells in the intestinal enteric nervous system might have causal link with the following appearance of Parkinson disease (for a review see e.g., Smith and Parr-Brownlie, 2019). Fatal familiar insomnia syndrome, which leads to progressive inability to sleep, also results in severe autonomic dysfunction finally finishing by death (Lugaresi and Provini, 2007).…”

Iron and manganese-related CNS toxicity: mechanisms, diagnosis and treatment

“…Food and supplements that were high in Fe (such as beef and multivitamins) were associated with more rapid PD progression. Analysis and optimization of the intestinal microbiome have also been suggested as a potential method to prevent or slow the onset of PD, since gastrointestinal issues often precede neurodegeneration in PD [110].…”