Review Suggests IBS Signals Higher Risk for Parkinson Disease Later in Life

Parkinson disease is believed to have a prodromal phase, long before neuronal death occurs, and some studies have focused on the gut-brain axis to look for clues.

Irritable bowel syndrome (IBS) could be an early warning sign of Parkinson disease (PD), according to a recent systematic review and meta-analysis examining potential links.

Gastrointestinal symptoms are the most common nonmotor symptoms in a majority of patients PD, and researchers are exploring some of the underlying pathological mechanisms and risk factors that both PD and IBS share. PD is believed to have a prodromal phase, long before neuronal death occurs, and some studies have focused on the gut-brain axis to look for clues.

In this study, researchers searched 2 databases up until August 2021 for research that fulfilled 4 points:

  • Observational studies, including case-control or nest-control or cohort studies
  • Studies that looked at the association between IBS and the risk of PD
  • Risk estimates with confidence intervals (CIs) or adequate data were provided to extract the risk estimates
  • The work were published as part of a full text

Case reports, animal studies, and reviews were excluded.

From 192 articles, 6 were ultimately chosen for analysis, involving 58,645 patients with PD. Risk estimates from the individual studies were pooled using random-effects models.

Results showed the overall risk for PD in patients who had IBS patients was significantly higher than the general population (odds ratio [OR], 1.5; 95% CI, 1.29–1.75; P < .001).

However, older patients with IBS (≥65 years) appeared to have higher risk (OR, 1.44; 95% CI, 1.3–1.59; P < .001) compared with patients aged 40 to 64 years (OR, 1.32, 95% CI, 1.05–1.64; P = .017).

Subgroup analysis revealed no significant differences in risk between men (OR, 1.47, 95% CI, 1.3–1.67; P < .001) and women (OR, 1.51, 95% CI, 1.29–1.75; P < .001).

The authors said exactly how IBS may increase the risk for PD is not fully known, but several pathways may be involved, including the microbiota-brain-gut axis. In a murine model of PD, dysbiosis of the gut microbiota was needed before the development of neuroinflammation and α-synuclein-mediated motor deficits; in addition, human gut microbiome alterations have been noted in other studies.

The authors said the low-grade intestinal inflammation of IBS may assist the development of PD, as the levels of inflammatory markers in PD are significantly higher than in healthy controls and correlate with the level of intestinal neuronal α-synuclein.

IBS may appear decades before PD’s hallmark motor symptoms appear. Two of the studies included in this review found that the risk of PD was highest during the 2 years of follow-up after diagnosis of IBS.

The authors said their review had the usual limitations common to meta-analyses, such as the small number of included studies and the observational, retrospective nature. The possibility of confounders exists, such as family history or lifestyle influences.

However, the review also had several strengths, including the fact that "the level of heterogeneity for the analyses was low, making the pooled results more convincing."


Lu S, Jiang HY, Shi YD. Association between irritable bowel syndrome and Parkinson's disease: a systematic review and meta-analysis. Acta Neurol Scand. Published online December15, 2021. doi:10.1111/ane.13570