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A review written by physicians from Cedars-Sinai Medical Center and recently published in Gastroenterology & Hepatology describes the clinical utility of breath testing for the diagnosis and treatment of both small intestinal bacterial overgrowth (SIBO) and intestinal methanogen overgrowth (IMO). Once lumped together under the SIBO umbrella, IMO was first proposed to be a distinct entity in 2020 as part of the American College of Gastroenterology’s clinical guidelines. While these two independent conditions have much in common with each other in regard to symptom presentation – i.e., non-specific GI symptoms such as bloating, abdominal discomfort/pain, flatulence, and constipation are common in both – IMO is characterized by an overgrowth of “methanogens” (methane-producing organisms) which are now recognized to be from the domain Archaea, and are not actually bacteria. These prokaryotic microorganisms may overgrow in the colon as well as the small intestine and may respond differently to antibiotic therapy compared to SIBO. Additionally, as methane slows intestinal transit time, those with IMO are more likely to have constipation (or IBS-predominant constipation). Other distinguishing characteristics include a greater likelihood of vitamin B12 deficiency among those with SIBO (44% increased risk), versus no change in risk for those with IMO. SIBO has also been associated with diabetes, Roux-en-Y gastric bypass, and prior cholecystectomy, while IMO has not.
It’s also important to point out that a substantial number of conditions have been associated with SIBO, including irritable bowel syndrome and inflammatory bowel disease, fatty liver, diabetes, pancreatic insufficiency, fibromyalgia, and many more. For example, a recent meta-analysis found SIBO to be roughly 5-fold more likely among people with celiac disease. While SIBO was not more likely to be found among celiacs that don’t respond to a gluten-free diet versus those that do, use of antibiotics among non-responders improved GI symptoms in nearly 96% of non-responders, strongly suggesting that testing and treating for SIBO among non-responders may be very helpful. Other risk factors for SIBO include the use of proton pump inhibitors (PPIs), which were associated with a 71% increase in risk for SIBO per a 2018 meta-analysis published in the Journal of Gastroenterology. PPIs may carry a stronger risk for IMO than SIBO per a recent case-control study.
Regarding SIBO, the two primary methods for diagnosis are aspiration of the small bowel during endoscopy or breath testing. Neither is considered to be a “gold standard,” as they both have limitations. A colony count of greater than or equal to 103 CFU/mL on aspiration is considered diagnostic of SIBO, but given that this method is costly, invasive, not well-standardized, and prone to contamination, it has significant limitations and is not frequently performed. For example, a nearly 20% contamination rate has been cited, and not all hydrogenogenic (hydrogen-producing) bacteria can be cultured.
Because of these limitations, breath testing is preferred for SIBO diagnosis, and the only choice for IMO (methanogens are not readily cultured). Following ingestion of either lactulose (10 g) or glucose (75 g), a rise in hydrogen of 20 ppm or more above baseline by 90 minutes is considered positive for SIBO, while a methane level of 10 ppm or more at any time during testing is indicative of IMO. A single fasting methane measurement of 10 ppm or more has also been suggested as a reasonably sensitive and specific alternative to use of either carbohydrate for the diagnosis of IMO.
Both lactulose and glucose are well-accepted for testing; lactulose may theoretically allow for detection of more distal SIBO given its complete resistance to absorption and digestion, though glucose may be more specific to SIBO, as it is likely to rule out colonic hydrogen production. A recent meta-analysis found glucose to have a superior sensitivity and specificity; 54.5% and 83.2% for glucose vs. 42% and 70.6% for lactulose, respectively. Yet the authors of the recent review conclude that each has its uses, and any determination of sensitivity and specificity is limited by a lack of a gold standard for comparison. Lactulose may be a better choice for diabetics and those with diarrhea-predominant IBS, while glucose may be preferable for those with more rapid orocecal transit times.
This review also describes two additional breath patterns that may give clinical insight. A “flat-line pattern,” defined as no methane and low fixed hydrogen (hydrogen baseline of ≤3 ppm which does not rise more than >1 ppm above baseline), is more likely to be observed among people with inflammatory bowel disease, following antibiotic use, or due to gastroparesis, and may warrant testing for hydrogen sulfide. Additionally, a high baseline hydrogen pattern (> 20 ppm baseline, with no methane) is a less common pattern, but one that might guide antibiotic therapy.
Growing research into SIBO and IMO suggests these common conditions are underdiagnosed. While present in at least a third of patients with gastrointestinal complaints, a review published in the World Journal of Gastroenterology reports over a 6-fold risk among people who smoke, nearly a 4-fold risk among people with metabolic associated fatty liver disease (MAFLD), over 4-fold among people with diabetes, a 22-fold risk for those with hypothyroidism, etc. This recent review provides a nice overview of testing considerations.
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