Role of small intestinal bacteria overgrowth in irritable bowel syndrome and anxiety: a retrospective Electronic Health Record (EHR)- based cohort study using triNetX

Abstract Aims : The goal of this study is to examine the relationship between small bacterial overgrowth (SIBO) and irritable bowel syndrome (IBS) with their subsequent risk of developing generalized anxiety disorder (GAD). Methodology : Data for this retrospective study was obtained through TriNetX, a global health research network that aggregates de-identified electronic health records from over 100 million patients across multiple healthcare organizations. Two cohorts of 7716 patients were identified. Cohort 1 consisted of IBS patients with SIBO and Cohort 2 consisted of IBS patients without SIBO. Patients included were aged 18 to 50 years. Patients with pre-existing diagnoses of GAD, panic disorder, or depressive episodes before IBS onset were excluded. Cohorts were matched for sex, race, ethnicity, gastroesophageal reflux disease, non-infective enteritis and colitis, and proton pump inhibitor use through logistic regression models. Results : IBS patients with SIBO (Cohort 1) demonstrated a GAD incidence of 6.36% compared to 4.71% in those without SIBO (Cohort 2), yielding an absolute risk difference of 1.66% (95% CI: 0.938%–2.38%, p<0.0001). Logistic regression revealed an odds ratio of 1.377 (95% CI: 1.197–1.583) for GAD development in Cohort 1. Cox proportional hazards modeling demonstrated a hazard ratio of 1.301 (95% CI: 1.136–1.491, p=0.0008), indicating that IBS patients with SIBO faced a significantly elevated and persistent risk of GAD development over the 15-year observation period. Discussion : IBS patients with comorbid SIBO have a significantly elevated risk of developing GAD compared to IBS patients without SIBO. These findings suggest that SIBO may amplify gut-brain axis dysfunction beyond what is observed in IBS alone.