Breath testing prior to SIBO treatment? Yes.

This is half of a two-part debate — read the opposing argument.

Breath testing for small intestinal bacterial overgrowth (SIBO) has been used in clinical gastroenterology for over three decades. However, in the last decade, there has been a renewed interest in this diagnostic test for identifying SIBO. The renewed interest in SIBO is related in part to better antibiotic approaches to the condition, as well as the increasing interest in the role the human microbiome plays in health and disease since the publication of the human microbiome project.1

Clinical breath testing is a non-invasive technique to determine the presence or absence of SIBO in patients complaining of bloating, distension and changes in bowel habits. Until recently, breath testing has suffered from a lack of clear validation and as such has been criticized for its wide spectrum of sensitivity and specificity.2 This lack of sensitivity and specificity has more to do with the lack of a true gold standard for SIBO. This has resulted in published studies with a wide range of outcomes for what is a positive breath test. Recently, the North American Consensus on breath testing set out to establish baseline standards for the reporting and interpretation of breath tests.3 While this is likely to change with better data, this provides an initial framework under which studies can be grounded.

The question for this article is whether in the era of safe and effective therapies for SIBO, breath testing should or needs to be done before therapy. Here, we present a number of arguments to support the notion that a breath should be done before implementing treatment.

To know if it is SIBO

Before using an antibiotic or other approach to the patient with symptoms consistent with SIBO, it is important to be sure that the patient has SIBO. The symptoms typical of SIBO, such as bloating, distension and diarrhea, are non-specific and as such are also seen in other conditions. For example, endometriosis can manifest the same symptoms. The argument here would be how to identify SIBO. Some centers advocate invasive testing to obtain duodenal or small bowel aspirates for culture. The challenge here is that this sort of testing is invasive, expensive and traditional techniques suffer from issues of contamination during sampling.

Breath testing, on the other hand, is a simple, non-invasive approach to improve the clinician’s suspicion for SIBO. Despite early criticism of the test, the REIMAGINE study presented at Digestive Disease Week® has validated new techniques for small bowel aspiration to optimize culture and deep sequencing of the small bowel microbiome. In addition, a subset of subjects had undergone breath testing.4 The study showed that sequencing and culture were in line and predicted symptoms consistent with SIBO. In addition, the study determined the ideal breath test result that predicted both culture, sequencing and symptoms. That cutoff was a rise of hydrogen during breath test of >20ppm by 90 minutes. This represents the first full validation of the lactulose breath test (not glucose).

The importance of methane testing

A second important reason to consider breath testing before treatment in the workup of SIBO is methane. The typical lactulose breath test incorporates the measurement of hydrogen and methane. While hydrogen had been the classic measure of SIBO, methane appears important as it predicts constipation.5 In fact, methane is the actual agent to produce constipation. Infusion of methane gas into the small intestine is shown to slow intestinal transit.6

More importantly, methane is a determinant of treatment. Unlike hydrogen SIBO, which usually responds to a single antibiotic, methanogens have a different response to antibiotics. This is demonstrated by a randomized controlled trial whereby subjects with constipation and methane were treated with either neomycin, with placebo or neomycin with rifaximin. In this study, the dual antibiotic approach produced a greater improvement in constipation and greater likelihood of methane reduction.7

Breath testing predicts response to antibiotics

Finally, it is important to assess whether breath testing is a predictor of outcomes in the treatment of SIBO. A number of studies have tried to answer this question. In an early double-blind study using rifaximin for the treatment of irritable bowel syndrome (IBS) with breath testing, Sharara, et al found that breath testing was a predictor of outcome after antibiotic use. The subjects with a response to therapy had a greater reduction in hydrogen on breath testing.8

In a more recent study, breath testing predicted treatment response using the new FDA endpoint in IBS subjects.9 This involved the analysis of a subset of IBS subjects who underwent lactulose breath testing in the TARGET 3 retreatment study using rifaximin.10 In this study, nearly 100 subjects had undergone breath testing prior to and after treatment with rifaximin. In the TARGET 3 trial, the overall FDA outcome response to rifaximin was 44%. However, subjects with a positive baseline breath test for hydrogen had a 56% rate of meeting the responder definition. More interesting was that if the subject’s breath test was positive and after treatment became normal, 76% of these subjects met the FDA responder endpoint. This argues that breath testing may enrich the likelihood of antibiotic therapy in SIBO, and also that breath testing has usefulness not only before treatment but after therapy as well.

In summary, breath testing has come a long way since the 1980s, and the evolution of breath testing continues as new fermentation products such as hydrogen sulfide are added and validated. The new data support that breath testing is an important part of the workup of patients with typical symptoms. Breath testing not only provides a diagnosis of SIBO, but  is now for the first time validated against both culture and deep sequencing. Methane is very important in the determination of not only constipation, but the selection of antibiotics to use. Finally, a recent study now shows that breath testing predicts the response to treatment. This will help enrich and maximize the benefits of therapy. Given the recent validation of the breath test, this further diminishes the need for invasive, expensive testing such as endoscopically obtained duodenal aspirates.

Dr. Quigley says we must agree on a definition of SIBO first.

Disclosures: Dr. Pimentel has no conflicts to disclose.

References

1. Turnbaugh P.J., Ley R.E., Hamady M., et al. The human microbiome project. Nature. 2007;449:804-810.
2. Khoshini R., Dai S.C., Lezcano S., et al. A systematic review of diagnostic tests for small intestinal bacterial overgrowth. Dig Dis Sci. 2008;53:1443-1454.
3. Rezaie A., Buresi M., Lembo A., et al. Hydrogen and methane-based breath testing in gastrointestinal disorders: The North American Consensus. Am J Gastroenterol. 2017;112:775-784.
4. Leite, G. et al. First large scale study defining the characteristic microbiome signatures of small intestinal bacterial overgrowth (SIBO): Detailed analysis from the REIMAGINE study. Gastroenterol. 2019;156:S1-2.
5. Kunkel D., Basseri R.J., Makhani M.D., et al. Methane on breath testing is associated with constipation: A systematic review and meta-analysis. Dig Dis Sci. 2011;56:1612-1618.
6. Pimentel M., Lin H.C., Enayati P., et al. A combination of rifaximin and neomycin is most effective in treating irritable bowel syndrome with methane on lactulose breath test. J Clin Gastroenterol. 2010;44:547-50.
7. Low K., Huang L., Hua J., et al. Pouch inflammation is associated with a decrease in specific bacterial taxa. Gastroenterology. 2015;149:718-27.
8. Sharara A.I., Aoun E., Abdul-Baki H., et al. A randomized, double-blind placebo-controlled trial of rifaximin in patients with abdominal bloating and flatulence. Am J Gastroenterol. 2006;10:326-33.
9. Lembo A., Pimentel M., Rao S.S., et al. Repeat treatment with rifaximin is safe and effective in patients with diarrhea-predominant irritable bowel syndrome. Gastroenterol. 2016;151;1113-1121.

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