Methane positive small intestinal bacterial overgrowth in inflammatory bowel disease and irritable bowel syndrome: a systematic review and meta-analysis

Several studies reported a potential role of methane producing archaea in the pathophysiology of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). We conducted a systematic review and meta-analysis to assess the prevalence of methane positive small intestinal bacterial overgrowth (SIBO) in IBS and IBD compared with controls. MEDLINE (PubMed) and Embase electronic databases were searched from inception until March 2021 for case-control and prevalence studies reporting SIBO in IBS and IBD. We extracted data from published studies and calculated pooled prevalence of SIBO in IBS or IBD, odds ratios (OR), and 95% CIs, utilizing a random effects model. The final dataset included 17 independent studies assessing the prevalence of methane positive SIBO in 1,653 IBS-patients and 713 controls, and 7 studies assessing the prevalence of methane positive SIBO in 626 IBD-patients and 497 controls, all utilizing breath test for SIBO diagnosis. Prevalence of methane positive SIBO in IBS and IBD was 25.0% (95% CI 18.8–32.4) and 5.6% (95% CI 2.6–11.8), respectively. Methane positive SIBO in IBS was not increased compared to controls (OR = 1.2, 95% CI 0.8–1.7, P = .37) but was significantly more prevalent in IBS-C as compared to IBS-D (OR = 3.1, 95% CI 1.7–5.6, P = .0001). The prevalence of methane-positive SIBO in patients with IBD was 3-fold lower at 7.4% (95% CI 5.4–9.8) compared to 23.5% (95% CI 19.8–27.5) in controls. The prevalence of methane positive SIBO was significantly lower in Crohn’s disease as compared to ulcerative colitis, (5.3%, 95% CI 3.0–8.5 vs. 20.2%, 95% CI 12.8–29.4). This systematic review and meta-analysis suggests methane positivity on breath testing is positively associated with IBS-C and inversely with IBD. However, the quality of evidence is low largely due to clinical heterogeneity of the studies. Thus, causality is uncertain and further studies are required.