SIBO and Intestinal Methanogen Overgrowth: Breath Test Performance, Treatment Response, and Relapse – A Systematic Review and Meta-Analysis

Background & Aims: Small intestinal bacterial overgrowth (SIBO) and intestinal methanogen overgrowth (IMO) are increasingly recognised in functional and structural gastrointestinal disorders, yet uncertainty persists regarding the accuracy of breath tests, the true effect of antibiotic and non-antibiotic therapies, and the risk of recurrence after apparent eradication. We conducted a comprehensive systematic review and meta-analysis to evaluate diagnostic performance, treatment efficacy and recurrence patterns, and to grade the certainty of evidence across these domains. Methods: We searched MEDLINE, Embase, Web of Science, CENTRAL and Scopus from inception to 30 November 2025, supplemented by trial registries and reference lists. Prospective diagnostic accuracy studies comparing glucose breath test (GBT) and/or lactulose breath test (LBT) with small-bowel aspirate culture, interventional studies of antibiotics, herbal antimicrobials or elemental diet, and cohorts reporting SIBO/IMO recurrence after eradication were included. Two reviewers independently performed screening, data extraction and risk-of-bias assessment (QUADAS-2, RoB 2, ROBINS-I, AMSTAR 2). Random-effects bivariate models were used for diagnostic accuracy and random-effects meta-analyses for treatment outcomes. Certainty of evidence was rated using GRADE. Results: Eighty-nine studies met inclusion criteria: 14 diagnostic accuracy studies (n = 757), 32 treatment studies, 18 systematic reviews/meta-analyses and 25 additional observational cohorts. GBT showed pooled sensitivity 54.5% and specificity 83.2% versus culture (diagnostic odds ratio [DOR] 5.17; area under the curve [AUC] 0.74), whereas LBT had sensitivity 42.0%, specificity 70.6% and AUC 0.56, indicating clearly inferior performance. Lower hydrogen cut-offs (10–15 ppm) and post–gastrointestinal surgery cohorts improved GBT accuracy (AUC up to 0.86). Rifaximin achieved pooled intention-to-treat eradication of 70.8% and per-protocol eradication of 72.9%, with adverse events in 4–5%. Across six randomized trials (n = 196), antibiotics increased global symptom response versus placebo (risk ratio 2.46; 95% CI 1.33–4.55). In methane-positive IMO, combination rifaximin–neomycin therapy yielded methane eradication rates of 87% and higher clinical response than either agent alone. Observational cohorts reported recurrence rates of approximately 40–45% within 9–12 months after successful eradication, with lower relapse when prokinetic maintenance was used. GRADE ratings were moderate for GBT accuracy and low for rifaximin eradication, symptom benefit, combination therapy in IMO and recurrence outcomes. Conclusions: GBT, interpreted with contemporary cut-offs, offers moderate, clinically useful accuracy and outperforms LBT as a non-invasive diagnostic test for SIBO. Rifaximin provides substantial but not definitive microbiological eradication and symptom relief, while combination therapy appears necessary for optimal management of methane-dominant IMO. High recurrence rates and low-certainty treatment evidence support viewing SIBO/IMO as chronic relapsing conditions that require integrated strategies targeting motility, structural risk factors and diet, alongside judicious antimicrobial use. Large, well-designed randomized trials with standardized diagnostic and outcome criteria are urgently needed to refine these estimates and guide precision management.