In a recent study published in npj Parkinson’s Disease, researchers explore the relationship between Parkinson’s disease (PD) and irritable bowel syndrome (IBS).

Study: Association between irritable bowel syndrome and Parkinson’s disease by Cohort study and Mendelian randomization analysis. Image Credit: Kotcha K / Shutterstock.com

What causes PD?

PD is a common neurodegenerative disease, with symptoms including resting tremors, bradykinesia, and stiffness. Typically, these symptoms arise several years before being diagnosed with PD, with cognitive impairment and gastrointestinal problems preceding motor symptoms.

The specific etiology of PD is unknown; however, the disease may caused by environmental and genetic factors. There is evidence linking PD to gastrointestinal symptoms, which might be related to changes in the gut microbiome, enhanced intestinal permeability, or gut-brain communication.

IBS is a functional gastrointestinal disease characterized by recurring or chronic abdominal discomfort and bowel alterations. Current research indicates a possible association between PD and IBS; however, the results of these studies have been inconsistent.

About the study

Data from the United Kingdom Biobank (UKBB) of 426,911 individuals between 40 and 69 years of age enrolled in 22 centers between 2006 and 2010 were used for the current analysis. Five healthy control individuals based on age and sex were also used for each IBS patient diagnosed at follow-up. All study participants were monitored until PD diagnosis, study termination in June 2023, or death, whichever occurred first.

Any individuals with missing data, as well as those with other neurological and gastrointestinal disorders, were excluded from the study. Likewise, any individuals diagnosed with PD before study initiation and those with indeterminate dates for IBS diagnosis were also excluded. Taken together, 26,944 individuals were diagnosed with PD and 2,460 with IBS using the International Classification of Disease-10 (ICD-10) codes.

Cox proportional hazard models were used to determine the hazard ratios (HRs), whereas logistic regression analysis was used to calculate the odds ratios (ORs) for the association between PD and IBS. Study covariates included age, sex, body mass index (BMI), Townsend deprivation index, educational attainment, ethnicity, smoking status, alcohol intake, overall health, and chronic medical conditions.

Sensitivity analyses were also performed by excluding individuals with self-reported IBS diagnoses and stratifying participants by IBS diagnosis before or after 2000. The association between PD and IBS was also analyzed by Mendelian randomization (MR) analyses using genotype data as instrumental variables, including simple mode, weighted mode, weighted median, MR Egger, and inverse variance weighting (IVW) methods.

Study findings

Of the 419,685 individuals involved in Cox modeling, 95% comprised the control study group, and 4.7% were diagnosed with IBS before study initiation. Both groups were monitored for a mean of 14 years.

As compared to controls, IBS patients were more likely to be female, less educated, non-smokers, consume less alcohol, have poorer health, and have more comorbidities. At follow-up, 90 IBS patients and 2,321 controls received a PD diagnosis, with incidence rates of 3.2 and 4.2 in 10,000 individual years in the case and control groups, respectively.

Univariable Cox regression analysis demonstrated that PD risk was reduced among IBS patients with an HR of 0.8. In a certain subgroup analyses, IBS individuals were associated with a reduced likelihood of developing PD, as did individuals receiving an IBS diagnosis after 2000 with an HR of 0.6.

Subgroup analysis revealed that IBS was associated with a lower incidence of PD among white individuals, individuals with a smoking history, BMI between 25-29.90, and less than college-level educational attainment, with HRs of 0.8, 0.6, 0.6, and 0.8, respectively.

IBS was significantly associated with 11 study covariates, including advanced age, male sex, and comorbidities, with HRs of 1.2, 2.1, and 1.7, respectively. Individuals who frequently consumed alcohol were also at a reduced risk of PD risk than occasional and non-consumers; however, for those with excess alcohol intake, this correlation was not apparent.

Logistic regression analysis revealed that IBS was unrelated to PD risk with an OR of 1.2. Likewise, MR analyses showed no significant evidence of causal associations between IBS and PD, with an OR of 0.8.

A significantly increased risk of PD was observed among non-IBS patients with a polygenic risk score of PD with an HR of 2.2. In the sensitivity analysis, excluding self-reported IBS patients yielded similar results.

Among individuals diagnosed with IBS after 2000, a reduced risk of PD was related to IBS with an HR of 0.6. Case-control analysis showed that IBS occurrence did not reduce PD risk, with MR analysis results supporting these findings.

Conclusions

IBS patients do not appear to be at a greater risk of developing PD; however, some patient subgroups may be less likely to be diagnosed with PD. Nevertheless, future studies are needed to better understand the potential relationship between IBS and PD and elucidate underlying mechanisms.