Parkinson’s Disease: Origins in the Gut?

Within the last few weeks, researchers at Mount Sinai have found strong correlations between Parkinson’s disease and the gut, confirming earlier studies that indicate the association.

A new genetic study demonstrates that several variants in the LRRK2 gene raise or lower risk not only for Parkinson’s, but also for Crohn’s disease: an inflammatory bowel disorder. The researchers identified a new functional risk variant, N2081D, which increases LRRK2’s kinase activity, in addition to a protective variant that inactivates lRRK2. The study’s researchers confirm that these findings may provide insight into underlying disease mechanisms, and point toward improved therapeutic approaches: LRRK2 inhibits being developed for Parkinson’s may help people with Crohn’s, while anti-inflammatory approaches could likewise benefit Parkinson’s patients.

Moreover, an earlier study published in Neurology, the official journal of the American Academy of Neurology, investigates the role of the vagus nerve in Parkinson’s disease–suggesting that a resection of the nerve might stop or delay the spreading of Parkinson’s disease, and providing further concrete evidence of the link between Parkinson’s and the gut.

Historically cited as the pneumogastric nerve, the theory suggests that the vagus nerve might serve as the channel for transporting the protein alpha-synuclein from stomach to brain, where it forms ‘telltale clumps in Parkinson’s sufferers.’

If accurate, the hypothesis points to a clear origin of the neurodegenerative brain disorder: the gut. Moreover, it would explain and confirm the critical importance of the enigmatic protein, whose exact role in Parkinson’s has previously not been well understood.  Perhaps most importantly, it would point to a potential way to block the development and progression of Parkinson’s: a surgical procedure known as a vagotomy, which is generally used in people with severe gastric ulcers, and involves cutting the vagus nerve in order to completely sever the ‘pathway from gut to brain.’

The objective of the published research was to examine whether vagotomy decreases the risk of Parkinson’s. Using comprehensive data from nationwide Swedish registers, the authors conducted a matched-cohort study of 9,430 vagotomized patients and 377,200 non-vagotomized patients. The researchers were aiming to find if the process of a vagotomy—in addition to a treatment for peptic ulcers—might lower the risk of Parkinson’s by blocking the route of alpha-synuclein to the brain.

After analyzing the data and assessing the subset of patients who received the most drastic version of the procedure, a truncal vagotomy—which removes the vagus nerve from contact with the liver, stomach, pancreas, gall bladder, small intestine, and proximal colon—they found that Parkinson’s disease was 22% less common than it was amongst people in the non-vagotomized comparison group.

While this study delivers clear epidemiological evidence to support the theory that Parkinson’s originates in the gut, previous studies further indicate that this may indeed be true. Alpha-synuclein protein clumps have been detected in the guts of patients with very early-onset Parkinson’s; in mice who had alpha-synuclein from the brains of human Parkinson’s patients implanted in their intestinal walls, researchers have seen movement of those proteins in the vagus nerve.

Our upcoming 26th Annual Spring Congress will focus on brain diseases and disorders, including the prevalence of Parkinson’s disease and related conditions. Our Module IV: Gastroenterology will also spotlight the gut-brain axis, and discuss the strong correlation between the gut microbiome and brain conditions.

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