OBJECTIVE: 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.
CONCLUSIONS: 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.

Elemental diets have been employed for the management of various diseases for over 50 years, with several mechanisms mediating their beneficial effects. Yet, they are underutilized due to poor palatability, access, cost, and lack of awareness regarding their clinical efficacy. Therefore, in this review, we aimed to systematically search and review the literature to summarize the formulation variability, mechanisms of action, clinical applications, and tolerability of the elemental diets in gastrointestinal diseases. While large prospective trials are lacking, elemental diets appear to exhibit objective and subjective clinical benefit in several diseases, including eosinophilic esophagitis, eosinophilic gastroenteritis, inflammatory bowel diseases, small intestinal bacterial overgrowth, intestinal methanogen overgrowth, chemoradiotherapy-associated mucositis, and celiac disease. Although some data support the long-term use of elemental diets as an add-on supplement for chronic pancreatitis and Crohn\'s disease, most of the literature on exclusive elemental diets focuses on inducing remission. Therefore, subsequent treatment strategies for maintaining remission need to be adopted in chronic/relapsing diseases. Several mechanistic pathways were identified to mediate the effects of elemental diets, including food additive and allergen-free content, high passive absorption rate, and anti-inflammatory properties. High rates of intolerance up to 40% are seen in the trials where exclusive elemental diets were administered orally due to poor organoleptic acceptability; however, when tolerated, adverse events were rare. Other limitations of elemental diets are cost, access, and lifestyle/social restrictions. Moreover, judicious use is advised in presence of a concomitant restrictive food intake disorders. Elemental diets offer a potentially highly efficacious dietary intervention with minor side effects. Palatability, cost, access, and social restrictions are common barriers of use. Prospective clinical trials are needed to elucidate the role of elemental formulas in the management of individual diseases.

BACKGROUND: The relationship between Helicobacter pylori (H. pylori) infection and small intestinal bacterial overgrowth (SIBO) has attracted attention recently.
OBJECTIVE: To analyze the influence of H. pylori infection and eradication on SIBO, IMO, and abdominal symptoms.
METHODS: Patients with gastrointestinal symptoms were tested for 13C urea breath test and if positive, treated with bismuth-based quadruple therapy. Lactulose hydrogen methane breath test (HMBT) was performed and symptoms were assessed using gastrointestinal symptom rating scale (GSRS) before and 6 weeks after eradication.
RESULTS: Of the 102 subjects, 53 were H. pylori positive. The prevalence of SIBO and IMO were higher in patients with H. pylori infection than in those without infection (49.1% vs 24.5%, P = 0.019 for SIBO; 24.5% vs 8.2%, P = 0.027 for IMO). GSRS scores were similar between H. pylori-infected and uninfected patients (2 (IQR: 1;3) vs 2 (IQR: 1;2), P = 0.211). Patients with SIBO or IMO presented higher GSRS scores than patients with both SIBO and IMO negative (2 (IQR: 2;3), 2 (IQR: 2;3) vs 2 (IQR: 1;2), P = 0.011, 0.001, respectively). For the 50 patients who successfully eradicated H. pylori, the response rates for SIBO and IMO were 66.7% and 76.9%, respectively. GSRS scores also significantly decreased (2 (IQR: 1;3) to 0 (IQR: 0;1), P < 0.001) after eradication.
CONCLUSIONS: Helicobacter pylori infection was associated with higher prevalence of SIBO and IMO, both of which led to more pronounced abdominal symptoms. H. pylori eradication also achieved therapeutic effects on SIBO and IMO, accompanied by relief of abdominal symptoms.

Breath testing is the most widely utilized modality to diagnose small intestinal bacterial overgrowth (SIBO) and/or intestinal methanogen overgrowth (IMO). Although SIBO can be diagnosed with small bowel aspiration and breath testing, IMO can only be diagnosed with breath testing in clinical practice. Breath testing can tailor antibiotic therapy and predict response to treatment; however, the test is limited by its indirect method of measurement and concerns about the variability of orocecal transit time. Like any clinical test, breath testing has inherent strengths and limitations, and results must be interpreted with consideration of the clinical context and influencing factors. Recent studies have demonstrated the expanding clinical utility of breath testing in the diagnosis, management, and prediction of treatment response in SIBO and particularly in IMO along with the identification of distinct breath test patterns such as flat-line and high baseline hydrogen. This article reviews the strengths and limitations of breath testing in diagnosing SIBO and IMO as well as its expanding utility in clinical practice.