Unique Differences in Breath Test Gas Patterns in Inflammatory Bowel Disease (IBD) Compared to Non-IBD Patients: A Large-Scale Database Linkage Analysis

Abstract

Introduction: Breath testing (BT) has gained interest for diagnosing small intestinal bacterial overgrowth (SIBO) in IBD patients with overlapping irritable bowel syndrome (IBS)-like symptoms. We aimed to characterize BT gas patterns in IBD patients compared to non-IBD patients and assess antibiotic response. Methods: A database of 14,847 consecutive lactulose BTs performed between November 2005 and October 2013 was developed from patients with IBS-like symptoms. Repeated BTs were excluded using probabilistic record linkage. BTs were classified into 5 categories: Normal: CH4 <10 parts per million (ppm) and H2 rise <20ppm within 90 min. H2predominant: CH4 <10ppm and H2 rise >20 ppm within 90 min, CH4 predominant: CH4 ≥10 ppm, Flatline: CH4 =0 ppm and H2≤3 ppm with variation ≤1 ppm within 120 min, Equivocal: H2 >20ppm at baseline. BT data was linked to our electronic health records to identify IBD patients and their disease course through manual chart review. Response to antibiotics was determined by reported improvement in symptoms. Poisson loglinear model was used assess differences in gas patterns between IBD and non-IBD patients. Results: After probabilistic linkage, we identified 455 IBD and 10,505 non-IBD patients with BT. Demographics and disease phenotypes are summarized in Table 1 and Table 2. SIBO was present in 58% (n=264) of IBD patients with IBS overlap. (Fig 1) Patients with Crohn's disease (CD) (effect size (ES) -1.48, [95% confidence interval (CI) -0.84- -2.13], p<0.001) and ulcerative colitis (UC) (ES -0.80, [95%CI -0.19- -1.14], p=0.01) were significantly less likely to produce excessive CH4 compared to non-IBD patients. When combined, IBD patients were more likely to be flatliner than non-IBD patients (ES 0.49, [95%CI 0.04-0.95], p=0.03). CH4predominant SIBO was significantly more prevalent in UC patients with constipation than other gas patterns (50%, p=0.001). In IBD patients with SIBO, 57% responded to antibiotics independent of disease activity, location, and behavior.679_A Figure 1. Cohort demographics of non-IBD patients compared to IBD patients.Conclusion: IBD patients with ongoing IBS-like symptoms have high prevalence of SIBO and demonstrate symptomatic improvement with antibiotics. Methanogenesis is suppressed in IBD patients. Flatline BT is more prevalent in IBD patients, suggesting excessive hydrogenotrophic bacteria. These findings suggest CH4 producing and hydrogenotrophic microorganisms as potential therapeutic targets. Future prospective studies are needed to validate these findings.679_B Figure 2. Disease phenotype of IBD patients.679_C Figure 3. Comparison of breath test patterns of CD, UC and non-IBD patients. Methanogenesis is significantly suppressed in CD and UC patients with IBS-like symptoms compared to non-IBD patients. There is no statistically significant difference between breath test patterns of CD and UC patients.