S2087 Clostridioides difficile Infection Increases the Risk of Belated Microscopic Colitis Development: A 20-Year Propensity-Matched, Multicenter, Cohort Study Across the United States

Introduction: Clostridioides difficile is an anaerobic gram-positive bacillus that is a leading cause of health-associated infectious diarrhea, primarily due to antibiotic-induced disruption of the normal gut microbiota. The bacterium’s pathogenicity is mediated by the production of 2 major exotoxins, leading to cytoskeletal disruption, loss of epithelial barrier function, cell death, and a devastating inflammatory response. Scattered case-control studies have recently noted that patients with C. difficile infection (CDI) have increased odds of developing microscopic colitis (MC), a chronic inflammatory disease characterized by watery diarrhea. To date, there is no nationwide or global study on this association. Methods: We conducted a retrospective nationwide cohort study on adults ≥50 years using the TriNetX database from January 2004 to May 2025. Two patient cohorts were generated via International Classification of Diseases, Tenth Revision coding – one with a diagnosis of enterocolitis due to CDI (A04.07) and the other with healthy patients with no CDI history (Z00.00). Evaluation for MC and its subtypes – lymphocytic colitis (LC) and collagenous colitis (CC) – within each cohort were then assessed, and 1:1 propensity score matching was completed for age, sex, race, medications, and autoimmune conditions to account for any confounding variables. Risk ratios with 95% confidence intervals (CI) were reported. Results: Our cohorts consisted of 287,128 patients each after 1:1 propensity score matching. The mean age was 68.2 years ± 12.6 with a demographic breakdown of 55% women, 75% White, and 11% Black. The median follow-up time to MC diagnosis was 671 days for CDI-positive patients and 1,427 days for CDI-negative patients. Compared with their noninfected counterparts, patients with CDI had a 1.9 relative risk of developing MC (95% confidence interval [CI] 1.69-2.02, P< 0.001]. Sub-stratifying this further, CDI-positive patients had a 2-fold relative risk of developing CC [95% CI 1.71-2.29, P< 0.001] and a 1.8 relative risk of developing LC [95% CI 1.51-1.94, P < 0.001] as compared to CDI-negative patients. Conclusion: This is the first nationwide cohort study investigating the relationship between MC and CDI. MC development is increased ∼2-fold after CDI in patients ≥50 years, even occurring years after the index infection. Patients with a prior CDI history presenting with chronic watery diarrhea should raise one’s suspicion for possible MC, as timely diagnosis and treatment can greatly improve quality of life and reduce unnecessary healthcare expenditures.