Abstract: Growing evidence suggests that there are similar pathological mechanisms and closely related pathogenic risk factors for inflammatory bowel disease (IBD) and Parkinson’s disease (PD). However, the epidemiological features of these two diseases are different. This review systematically evaluated the relationship between inflammatory bowel diseases and Parkinson’s disease risk. We searched PubMed, Embase, and Cochrane databases to retrieve observational studies of IBD and PD published from inception to October 2019. Nine observational studies, involving 12,177,520 patients, were included in the final analysis. None of the studies had Newcastle–Ottawa Scale scores that suggested a high risk of bias. After adjusting for confounders and excluding heterogeneous studies, the overall risk of PD was significantly higher in IBD patients than in the general population (adjusted risk ratio [RR] = 1.24, 95% confidence interval [CI]: 1.15–1.34, P < 0.001). A meta-analysis of the temporal relationship revealed that the incidence of IBD was significantly increased before (adjusted hazard ratio [HR] = 1.26, 95% CI: 1.18–1.35, P < 0.001) and after (adjusted RR = 1.40, 95% CI: 1.20–1.80, P < 0.001) PD diagnosis. After excluding a heterogeneous study, the pooled risk of PD development in patients with ulcerative colitis (adjusted HR = 1.25, 95% CI: 1.13–1.38, P < 0.001) or Crohn’s disease (adjusted HR = 1.33, 95% CI: 1.21–1.45, P < 0.01) was significantly increased. Subgroup analysis revealed no significant differences in risk between men (adjusted HR = 1.23, 95% CI: 1.10–1.39) and women (adjusted HR = 1.26, 95% CI: 1.10–1.43); however, older (> 65 years old) IBD patients (adjusted HR = 1.32, 95% CI: 1.17–1.48) may have a higher risk than younger (≤ 65 years old) patients (adjusted HR = 1.24, 95% CI: 1.08–1.42). Patients with IBD who were not treated with anti-tumor necrosis factor-α or azathioprine had significantly higher PD risk (adjusted HR = 1.6, 95% CI: 1.2–2.2). Thus, our meta-analysis indicates a certain correlation between IBD and PD, and suggests that IBD may moderately increase PD risk regardless of sex, especially in patients over 65 years of age. Moreover, early anti-inflammatory therapies for IBD might reduce the risk of developing PD. Our findings suggest an urgent need for an individualized screening strategy for patients with IBD. However, most studies included in this paper were observational, and more randomized controlled trials are needed to confirm the precise association between IBD and PD.

Key words: brain-gut axis, central nervous system, Crohn’s disease, inflammatory bowel diseases, meta-analysis, neurodegenerative disease, neuroinflammation, Parkinson’s disease, systematic review, ulcerative colitis