The Missing Piece Towards Improving And Standardizing SIBO Breath Tests

I have irritable bowel syndrome (IBS). Research suggests Small Intestinal Bacterial Overgrowth can explain IBS symptoms in as much as 78% of the cases (1). So, I reached out to the top doctors across the country to get properly tested and diagnosed. Here is what I found out:

  • Stanford and Augusta recommend SIBO detection via Glucose breath tests
  • Cedars Sinai recommends Lactulose breath test
  • Mayo Clinic does not recommend doing a SIBO breath test at all for IBS-C patients

If the top institutes cannot agree on an important protocol to identify whether problem lies in the small intestine, then the patients don’t have a prayer to get properly diagnosed and treated. There have been efforts to drive consensus (2) but so far that has not moved the needle for something as basic as deciding between Glucose vs Lactulose breath test. So, what is the problem? Let’s dig deeper. There are two mainstream approaches to do SIBO breath tests:

  • Glucose Breath Test: The problem with this test is that Glucose is absorbed within the first few feet of the small intestine, and therefore unable to detect bacterial overgrowth in the distal regions (3). The glucose breath test has a sensitivity of paltry 40%. I’m not aware of any other test across medical fields that has such a low sensitivity. Imagine being transparent with a patient in advance that this test will only detect their problem 40% of the time. How many patients would be willing to pay?
  • Lactulose Breath Test: The problem with this test is that lactulose is not absorbed in the small intestine and goes all the way to colon, where bacterial presence is normal. The widely accepted proposal is to use 90 minutes as a criterion to differentiate whether the gas production is from small intestine or colon. But, why 90 minutes? There is no good answer. The transit time has been shown to vary greatly depending upon demographics, even more so within people whose digestive health is compromised (1). In fact, nine out of eleven healthy subjects in this study had a false positive based on this 90-minute diagnostic criterion (3) .

So, we have two less than perfect tests. The glucose test is not sensitive enough and lactulose test produces way too many false positives. The key to wider adoption will not be standardization of these existing imperfect tests, but real improvements in sensitivity and specificity of these tests to well above 90%. One approach to make this possible maybe concurrent use of scintigraphy with lactulose breath test.

In scintigraphy, lactulose can be labelled with indium or technetium, and sequential scans can be obtained over the duration of simultaneous lactulose breath test (4). This approach can tell exactly when a significant amount of lactulose (say 10 – 25 %) reaches cecum, and that time can be used as cut-off for monitoring rise in gases for the lactulose breath test. Concurrent scintigraphy will take the debate out of an arbitrary 90-minute threshold, and significantly boost the specificity of lactulose breath test.

Scintigraphy is not a new approach, so why not use it together with breath tests? Firstly, it will be an additional test that comes with its cost burden. Further, due to the imaging requirements, scintigraphy can’t be done easily in a home environment like breath tests can be done. Moreover, it would need to be standardized for clinical practice. But with all its disadvantages, concurrent scintigraphy will give a legitimacy to the breath tests. Patients will have a diagnosis that all stakeholders would be able to trust. The breath tests as they exist today are simple, cheap, and can be done from the convenience of patient’s home. However, they are also worse than flipping a coin when it comes to their sensitivity and specificity. There is a hope that innovative ingestible capsules will completely change the way breath tests are done (5,6). However, we should not punt these problems to a future innovation. The patients today deserve better. Let’s bring the much-needed rigor in the breath testing protocol by adding concurrent scintigraphy.  

References

1.            Ghoshal UC, Shukla R, Ghoshal U. Small Intestinal Bacterial Overgrowth and Irritable Bowel Syndrome: A Bridge between Functional Organic Dichotomy. Gut Liver. 2017 Mar;11(2):196–208.

2.            Rezaie A, Buresi M, Lembo A, Lin H, McCallum R, Rao S, et al. Hydrogen and Methane-Based Breath Testing in Gastrointestinal Disorders: The North American Consensus. Am J Gastroenterol. 2017 May;112(5):775–84.

3.            Pimentel M, Saad RJ, Long MD, Rao SSC. ACG Clinical Guideline: Small Intestinal Bacterial Overgrowth. Official journal of the American College of Gastroenterology | ACG. 2020 Feb;115(2):165–78.

4.            Mangerson J, Bratten J, Stewart S, Jones M. Scintigraphy to validate lactulose hydrogen breath testing as a diagnostic tool for small intestinal bacterial overgrowth. Journal of Nuclear Medicine. 2008 May 1;49(supplement 1):427P-427P.

5.            Szarka LA, Camilleri M. METHODS FOR THE ASSESSMENT OF SMALL BOWEL AND COLONIC TRANSIT. Semin Nucl Med. 2012 Mar;42(2):113–23.

6.            Kalantar-Zadeh K, Berean KJ, Ha N, Chrimes AF, Xu K, Grando D, et al. A human pilot trial of ingestible electronic capsules capable of sensing different gases in the gut. Nat Electron. 2018 Jan;1(1):79–87.