Parkinson’s disease pathology starts years, even decades, before symptoms develop, and several studies support the link between conditions involving the gastrointestinal tract and Parkinson’s disease. Braak’s hypothesis is the theory that pathogens or toxins entering the gut or the olfactory mucosa may trigger the misfolding of alpha-synuclein, a key component of Lewy bodies. Lewy bodies may then spread to the nervous system, eventually leading to motor symptoms of Parkinson’s disease. A recent study published in Neurogastroenterology is the first multicenter study to examine the relationship between a wide variety of gastrointestinal conditions and the risk of a Parkinson’s disease diagnosis.

Study authors used a nationwide electronic health record network with data from more than 80 million patients to determine the incidence of gastrointestinal disorders before the onset of Parkinson’s. The case-control design also included patients with Alzheimer’s disease or cerebrovascular disease as well as negative controls; the design reduced the possibility of surveillance bias. A cohort study design then validated the findings and established relative risk estimates.

The two complementary study designs determined that dysphagia, gastroparesis, constipation, and inflammatory bowel syndrome (without diarrhea) increased the risk of a subsequent new onset diagnosis of idiopathic Parkinson’s compared with other neurological diseases, such as Alzheimer’s disease and cerebrovascular disease. Appendectomy was associated with a relative risk reduction of 52% in the cohort analysis of this study. Evidence from prior studies regarding the impact of appendectomy on Parkinson’s disease risk has been conflicting, but evidence suggests that the appendix constitutes a prominent source of seeding pathologically folded alpha-synuclein and houses bacteria capable of releasing inflammatory mediators.

Watch for our next Insights post about how the immune system may be involved in the pathogenesis of Parkinson’s disease.