Long-term risk of irritable bowel syndrome associated with social isolation and loneliness: a large-scale prospective cohort study with mediation analysis

Background: Social isolation and loneliness are common among older adults and have been linked to metabolic disorders, psychological conditions, and unhealthy lifestyle behaviors. However, their associations with incident irritable bowel syndrome (IBS) remain unclear. Objective: To investigate the associations of social isolation and loneliness with incident IBS risk, and the mediating roles of anxiety or depression. Design: Population-based prospective cohort study. Methods: Participants without IBS and with available social isolation and loneliness data at recruitment were included ( N = 394,458). Social isolation was assessed using household size, social contact frequency, and weekly social activities, while loneliness was measured by self-reported feelings of loneliness and willingness to confide. The primary outcome was incident IBS. Cox regression with sequential mediation analysis was conducted to estimate the effect. Results: During a median follow-up of 14.5 years, 8307 (2.1%) incident IBS cases were identified. Overall, 209,081 (53.0%), 149,729 (38.0%), and 35,648 (9.0%) participants were classified as least, moderately, and most isolated, respectively. The 14-year cumulative incidence of IBS increased from 2.0% (95% confidence interval (CI): 2.0–2.1) in the least isolated group to 2.2% (95% CI: 2.2–2.3) and 2.6% (95% CI: 2.4–2.8) in the moderately and most isolated groups (population-attributable fraction (PAF) = 3.6%). Compared with the least isolated group, most isolated individuals had a 20.0% higher IBS risk (hazard ratio (HR) = 1.20, 95% CI: 1.11–1.29), with 24.7% of the effect mediated by depression or anxiety. The 14-year cumulative incidence of IBS was 3.1% (95% CI: 2.9–3.4) in the lonely group versus 2.1% (95% CI: 2.1–2.1) in the non-lonely group (PAF = 2.1%). Compared with non-lonely individuals (95.2%), lonely individuals (4.8%) showed a 46.0% increased IBS risk (HR = 1.46, 95% CI: 1.34–1.59), with 26.5% of the effect mediated by depression or anxiety. In addition, one increment in social isolation score (HR = 1.08, 95% CI: 1.04–1.11) and loneliness score (HR = 1.27, 95% CI: 1.23–1.32) were associated with 8.0% and 27.0% higher IBS risk, respectively. Particularly, most isolated and lonely individuals exhibited a 60.0% greater IBS risk versus their non-lonely and least isolated counterparts (HR = 1.60, 95% CI: 1.35–1.89). Conclusion: Both social isolation and loneliness are associated with increased IBS risk, partially mediated by depression or anxiety. Multi-level psychosocial and environmental interventions may help reduce IBS burden.