Introduction
Recent research has highlighted the potential role of the brain–gut axis in the development of Parkinson’s disease (PD). Some studies suggest that disorders of gut brain interaction (DGBI) including irritable bowel syndrome (IBS) without diarrhoea, functional dyspepsia (FD) and chronic idiopathic constipation (CIC), may increase the risk of a subsequent PD diagnosis (1). However, findings remain inconsistent; for example, a recent prospective cohort study using Mendelian randomization found no significant association between IBS and the risk of developing PD (2).
Aims & Methods
Given these conflicting results, we aimed to investigate whether DGBI are associated with PD in a large sample of primary care patients. Data was collected from a retrospective cohort study of 1,129,104 patients attending general practices in the United Kingdom. Medical records were searched for a diagnosis of a DGBI (IBS, FD or CIC) and PD were included over an average of 15 years. Multiple logistic regression was used to assess the association of DGBI and a diagnosis of PD, adjusting for age and sex.
Results
The prevalence of IBS, FD and CIC and PD was 12.6%, 17.6%, 1.2% and 0.5% respectively. CIC and FD reported at any time were significantly more common in people with PD whereas IBS (all subtypes) was significantly less common (Table 1).
| Parkinson's Disease Diagnosis
No (n=1,123,843)
n (%) | Parkinson's Disease Diagnosis
Yes (n=5,261)
n (%) | P value |
| DGBI at any time relative to Parkinson's diagnosis |
|
|
|
| IBS (yes) | 141,630 (12.6) | 352 (6.7)
| <0.001 |
| FD (yes) | 197,348 (17.6) | 1,071 (20.4) | <0.001 |
| CIC (yes) | 13,411 (1.2) | 172 (3.3) | <0.001 |
| DGBI prior to Parkinson's diagnosis |
|
|
|
| IBS (yes) | 141,630 (12.6) | 300 (5.7) | <0.001 |
| FD (yes) | 197,348 (17.6) | 723 (13.7) | <0.001 |
| CIC (yes) | 13,411 (1.2) | 74 (1.4)
| 0.16 |
When examining pure DGBI reported at any time, we found that having CIC alone was associated with an increased risk of PD (OR = 2.62, 95% CI 2.20–3.12, p <0.001). FD (OR = 1.15, 95% CI 1.07–1.24, p < 0.001) and having two or more DGBI (OR = 1.45, 95% CI 1.20–1.75, p < 0.001) were also associated with a modestly significant increased risk of PD, even after controlling for age and sex. In contrast, IBS was not significantly associated with PD in the adjusted model.
When assessing DGBI prior to PD onset, chronic constipation was more common in those with PD but this was not significant (Table 1). On the other hand, IBS and FD were less common among individuals with new onset PD (Table 1). In a model examining pure DGBI categories prior to PD, IBS only (OR = 0.51, 95% CI 0.43–0.59, p < 0.001), FD only (OR = 0.26, 95% CI 0.23–0.30, p < 0.001), CIC only (OR = 0.36, 95% CI 0.24–0.54, p < 0.001), and having two or more DGBI (OR = 0.70, 95% CI 0.55–0.89, p = 0.003) were all inversely associated with PD after adjusting for age and sex.
Conclusion
We observed constipation is a risk factor for Parkinson’s disease, but this may be mostly explained by the neurologic disease process inducing bowel dysfunction. While IBS was not associated with Parkinson’s disease in any of the current analyses, we could not subdivide IBS into constipation versus non-constipation subgroups in this dataset (as this diagnostic information was not coded) so an association may have been missed.
References
- Konings B, et al. Gastrointestinal syndromes preceding a diagnosis of Parkinson's disease: testing Braak's hypothesis using a nationwide database for comparison with Alzheimer's disease and cerebrovascular diseases. Gut. 2023;72(11):2103-2111.
- Wang ZY, et al. Association between irritable bowel syndrome and Parkinson's disease by Cohort study and Mendelian randomization analysis. NPJ Parkinsons Dis. 2024 Mar 28;10(1):70.
