Symptom Profile of Patients With Intestinal Methanogen Overgrowth: A Systematic Review and Meta-analysis.

Background & Aims: Archaea constitute one of the main 3 domains of the tree of life, distinct from eukaryotes and bacteria. Excessive luminal loads of methanogenic archaea (intestinal methanogen overgrowth [IMO]) have been implicated in the pathophysiology of various diseases, including constipation. To elucidate the phenotypical presentation of IMO, we performed a systematic review and meta-analysis of the prevalence and severity of gastrointestinal symptoms in subjects with IMO as compared with subjects without IMO.

Methods: Electronic databases, including OVID MEDLINE and Cochrane Database from inception until September 2023, were systematically searched. Prevalence rates, odds ratios (ORs), standardized mean difference (SMD), and 95% confidence intervals (CIs) of symptoms were calculated.

Results: Nineteen studies were included (1293 patients with IMO and 3208 controls). Patients with IMO exhibited various gastrointestinal symptoms, including bloating (78%), constipation (51%), diarrhea (33%), abdominal pain (65%), nausea (30%), and flatulence (56%). Patients with IMO had a significantly higher prevalence of constipation as compared with controls (47% vs 38%; OR, 2.04; 95% CI, 1.48-2.83; P < .0001) along with lower prevalence of diarrhea (37% vs 52%; OR, 0.58; 95% CI, 0.37-0.90; P = .01) and nausea (32% vs 45%; OR, 0.75; 95% CI, 0.60-0.94; P = .01). Patients with IMO had higher severity of constipation (SMD, 0.77; 95% CI, 0.11-1.43; P = .02) and lower severity of diarrhea (SMD, -0.71; 95% CI, -1.39 to -0.03; P = .04). Significant heterogeneity was detected.

Conclusion: Patients with IMO exhibit a higher rate and severity of constipation along with lower rate and severity of diarrhea. The distinct phenotype of patients with IMO should be incorporated in patient-reported outcome measures and further correlated with mechanistic microbiome studies.