Risk of systemic rheumatic diseases in people with irritable bowel syndrome: a global-federated cohort analysis

Irritable bowel syndrome (IBS) is a prevalent disorder of gut-brain interaction increasingly linked to immune and inflammatory dysregulation. Whether IBS predisposes to systemic rheumatic diseases remains uncertain.

We conducted a retrospective cohort study using the TriNetX Global Collaborative Network, which integrates anonymized electronic health records from more than 150 healthcare organizations and 150 million patients worldwide. Adults (≥18 years) diagnosed with IBS (≥2 visits) between 2015 and 2023 were compared with matched controls undergoing routine health evaluations without IBS. Exclusion criteria included malignancy, pre-existing systemic rheumatic diseases, and death before the index date. Propensity score matching (1:1) balanced demographics, comorbidities, psychiatric disorders, and socioeconomic factors. The primary outcome was incident systemic rheumatic disease, categorized into inflammatory arthritis (ankylosing spondylitis, psoriatic arthritis, rheumatoid arthritis, gout) and connective tissue disorders (systemic lupus erythematosus, systemic sclerosis, Sjögren syndrome, dermatomyositis/polymyositis). Risk estimates were generated using the TriNetX analytic function, reporting hazard ratios with 95% confidence intervals. Sensitivity analyses included alternative definitions, extended washout periods (24 and 36 months), varying follow-up durations, active comparator cohorts, and negative controls. Cross-dataset validation was performed using the TriNetX US Collaborative Network.

After matching, 459966 patients were included in each cohort. Irritable bowel syndrome was associated with increased risks of ankylosing spondylitis (HR 2.57, 95% CI 2.22-2.98), psoriatic arthritis (HR 2.03, 95% CI 1.80-2.29), rheumatoid arthritis (HR 1.42, 95% CI 1.28-1.56), and gout (HR 1.34, 95% CI 1.27-1.42). Elevated risks were also observed for systemic lupus erythematosus (HR 1.84, 95% CI 1.65-2.04), Sjögren syndrome (HR 2.84, 95% CI 2.60-3.12), systemic sclerosis (HR 2.09, 95% CI 1.64-2.67), and dermatomyositis (HR 1.52, 95% CI 1.11-2.07). These associations remained across multiple sensitivity and stratified analyses.

IBS was associated with a higher risk of diverse systemic rheumatic diseases. Further studies are warranted to clarify the mechanisms underlying these observed associations.