Distinctive Clinical Correlates of Small Intestinal Bacterial Overgrowth with Methanogens

  • Katelyn E. Madigan
    Department of Internal Medicine, Wake Forest School of Medicine, Winston Salem, North Carolina
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  • Richa Bundy
    Department of Internal Medicine, Wake Forest School of Medicine, Winston Salem, North Carolina
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  • Richard B. Weinberg
    Reprint requests Address requests for reprints to: Richard B. Weinberg, MD, Wake Forest School of Medicine, Department of Internal Medicine, One Medical Center Boulevard, Winston-Salem, North Carolina 27157. fax: (336) 713-7322.
    Department of Internal Medicine-Gastroenterology, Wake Forest School of Medicine, Winston Salem, North Carolina

    Department of Physiology & Pharmacology, Wake Forest School of Medicine, Winston Salem, North Carolina
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Published:September 28, 2021DOI:

      Background and Aims

      Most patients with small intestinal bacterial overgrowth (SIBO) produce hydrogen by fermentation of dietary carbohydrates; however, ∼30% of patients with SIBO are colonized with Archaea, anaerobic organisms that produce methane. SIBO is associated with a plethora of symptoms and conditions, but their diagnostic significance is unclear. We aimed to determine if specific symptoms and conditions are associated with methanogenic SIBO.


      This study received institutional review board approval (IRB00059873). In this retrospective cross-sectional study, we queried a database of glucose breath tests conducted for suspected SIBO at our tertiary care medical center, which included data on the presence or absence of gastrointestinal symptoms and conditions often associated with SIBO. All patients had undergone a standardized breath testing protocol.


      In a cohort of 1461 patients, 33.1% were SIBO positive; of these, 49.8% produced only hydrogen, 38.8% produced only methane, and 11.4% produced both gases. The following factors distinguished patients with hydrogen-producing SIBO, but not methanogenic SIBO, from SIBO-negative patients: vitamin B12 deficiency (odds ratio, 1.44; confidence interval [CI], 1.01–2.06; P = .046), Roux-en-Y gastric bypass (odds ratio, 2.14; CI, 1.09–4.18; P = .027), cholecystectomy (odds ratio, 1.42; CI, 1.06–1.91; P = .020), and diabetes (odds ratio, 1.59; CI, 1.13–2.24; P = .008). The absence of vitamin B12 deficiency was the sole discriminating factor between methanogenic and hydrogenic SIBO (odds ratio, 0.57; CI, 0.34–0.97; P = .038).


      Patients with SIBO caused by methane-producing Archaea display a different spectrum of associated symptoms and clinical conditions compared with patients with SIBO caused by hydrogen-producing bacteria, particularly a lower incidence of vitamin B12 deficiency.

      Graphical abstract


      Abbreviations used in this paper:

      AUC (area under the curve), CI (confidence interval), CH4 (methane), GI (gastrointestinal), H2 (hydrogen), RYGB (Roux-en-Y gastric bypass), SIBO (small intestinal bacterial overgrowth)
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