In the first article of this series about Small Intestinal Bacterial Overgrowth (posted here), I covered what SIBO is and how common it is, as well as its symptoms. If you haven’t yet, I’d encourage you to read that article first as it will serve as a good introduction. In this second article, I cover the different tests used in diagnosing SIBO, as well as some of the advantages and drawbacks of each. In the next article will cover various treatment options for SIBO, including dietary protocols combined with antibiotic or herbal therapies (which interestingly have been found in research studies to be equally effective as the first-line antibiotic).
Diagnosing SIBO
One of the first challenges in diagnosing SIBO is finding a physician that is knowledgeable about the condition and current in its treatment. In the past only gastroenterologists diagnosed and treated SIBO and only after very invasive and expensive surgical tests were performed.
Before the invention of endoscopy, diagnosing SIBO required an invasive surgical procedure where a gastroenterologist would take a small amount of liquid from the jejeunum of the small intestine, and that fluid would be cultured to see what types of bacteria grew, and in what quantities. A positive diagnosis of SIBO would occur when > 104 colony-forming units of bacteria grew per milliliter of jejunal liquid [1]. The problem with this type of testing was that it was very invasive and expensive.
The medical invention of the endoscope in the mid-1980s enabled gastroenterologists to obtain fluid from the duodenum of the small intestine using a much less invasive procedure. In endoscopy, a long, flexible tube (endoscope) is passed into the throat of a sedated patient, then into the esophagus, past the stomach and into the duodenum, where a fluid sample is collected for culturing. One drawback to this test was that the sample was easily contaminated as it was withdrawn and the procedure was still quite invasive and expensive [1]. A second drawback is that only 30% of gut bacteria taken from the small intestine in this procedure and the one above are able to be cultured [3]. This surgical test is still invasive and expensive and as such is not widely used, although it is still considered the “gold standard” for diagnosing SIBO [2].
A brilliantly simple solution to testing for SIBO came as the result of the discovery that certain gases such as hydrogen or methane are only produced in the small intestine as the by-product of unabsorbed or incompletely absorbed carbohydrate in the diet. Simple breath tests to detect the presence of either gas provides not only the evidence of carbohydrate malabsorption (such as lactose and fructose malabsorption [3]), but the specific gas produced indicates the types of bacteria that are fermenting them (more on that below). The two breath tests for diagnosing SIBO that have become the most widely used are the glucose breath test and the lactulose breath test.
Glucose Breath Test or Lactulose Breath Test?
Either lactulose or glucose are used as substrates in hydrogen and methane breath testing for diagnosing SIBO, with some believing that glucose provides greater test accuracy [2] because glucose is absorbed completely in the upper small intestine [3], but may not be able to detect SIBO in the ileum, the far part of the small intestine, that connects to the large intestine [3]. Lactulose may be able to detect small-bowel bacterial overgrowth in the ileum [2,3].
Depending on which clinician one goes to, they likely will have a preference for using either glucose or lactulose breath test for diagnosing SIBO, whereas some gastroenterologists prefer to use jejeunal sampling via endoscopy.
How Does a Breath Test Work?
Hydrogen or methane exhaled in the breath following consumption of either glucose or lactulose is estimated using a gas chromatograph.
Normally, a small amount of hydrogen is produced from the limited amounts of unabsorbed carbohydrate that reaches the large intestine, however large amounts may be produced if there is malaborption of carbohydrate (such as fructose or lactose) in the small intestine, or if there are the wrong types of bacteria in the small intestine.
The hydrogen (or methane) is produced by the bacteria in the intestine, absorbed through the wall of the small-intestine, large-intestine or both, and the the hydrogen (or methane) containing blood travels up to the lungs. During a breath test, the hydrogen (or methane) is exhaled in the breath, and measured by the gas chromograph.
It is estimated that about 15%-30% of people have gut bacteria that contain Methanobrevibacter smithii, a methane-producing bacteria that recycles hydrogen by combining it with carbon dioxide, to produce methane. This bacteria converts 4 atoms of hydrogen into 1 molecule of methane [4], so people with this intestinal bacteria won’t exhale much hydrogen during the breath test (even if they have carbohydrate malabsorption or SIBO) because the hydrogen that they produce is converted into methane [3].
How the Breath Test is Performed
The person having the breath test first needs to fast overnight and have to brush their teeth and rinse their mouth with mouthwash to make sure oral bacteria don’t affect the test. At baseline, fasting breath hydrogen is estimated 3 – 4 times and averaged as basal breath hydrogen. If the person is found to have high breath hydrogen before they eat the sugar, then it may be attributed to SIBO. Then the person eats a specific amount of the test sugar; either 10 g lactulose or 100 g glucose, and the person’s breath is analyzed for hydrogen and methane every 15 minutes for 2 to 4 hours [3]. Diagnosing SIBO on the basis of a glucose breath test requires a rise in breath hydrogen by 12 ppm above baseline [3].
Based on a study published in 2000, Dr. Mark Pimentel, a key researcher in the area of SIBO from Cedar-Sinai Medical Center believes that a rise in breath hydrogen 20 ppm above basal levels within 90 minutes in a lactulose breath test should be considered a positive diagnosis of SIBO [5]. Some researchers maintain [3] that lactulose should not be used at all for diagnosing SIBO because it assumes that the time from when the lactulose is eaten until it reaches the junction of the small and large intestine (the cecum) is always greater than 90 minutes, whereas other studies indicate that it can range from 40 to 110 minutes [6]. As well, use of lactulose may only be able to diagnose 1/3 of people with SIBO [3].
A recent consensus paper from 2017 [7] published by 10 medical doctors involved in The North American Consensus group on hydrogen and methane-based breath testing concluded that both glucose breath testing and lactulose breath testing were reliable and were considered the least invasive tests for diagnosing SIBO [7]. The consensus group considered a rise in hydrogen of ≥20 ppm by 90 minutes* during glucose or lactulose breath test for SIBO to be positive for SIBO, and methane levels ≥10 ppm was considered methane positive.
*It should be noted that some clinicians such as Dr. Mark Pimentel consider a positive hydrogen test to be anything >20 ppm, and not necessarily a 20 ppm rise above baseline. In addition, Dr. Pimentel considers a positive methane test to be a reading of >3 PPM within 90 minutes (which is significantly lower than the levels set by the consensus group, of which he was a part [8]). Since different clinicians use different cutoff points to indicate a positive test for SIBO, this leads to what some consider to be a tendency to “overdiagnose” the condition [3].
As mentioned above, since a hydrogen breath test using glucose may miss SIBO in the far part of the small intestine (ileum), and a hydrogen breath test using lactulose may only be able to diagnose 1/3 of people with SIBO, some practitioners take the approach to treat patients “as if” positive for SIBO, in the absence of a positive breath test. If the person gets better on antimicrobial therapy along with appropriate dietary support, then it is deemed that the end goal for the person to feel better has been reached. There are two challenges that come to mind with respect to this approach; first of all, often more than one round of antibiotics or herbal antimicrobials are needed to completely eradicate the bacteria population in the small intestine that are responsible for the symptoms of SIBO. Does one do one round of treatment and hope for the best, or two rounds as that is the most likely to be effective? While Generally Recognized As Safe, even herbal treatments are not without risks, so treating “as if” is not a preferred option. The second drawback (that I will cover just below) is that the treatment for methane-dominant bacteria is different than the treatment for hydrogen-dominant bacteria. One could treat with herbal antimicrobials based on symptoms (i.e. the presence of constipation), but having a positive methane breath test (perhaps at the level of positive indicated by the consensus report, above) would enable an evidence-based treatment decision. While not without drawbacks, it is my opinion that breath testing should at least be tried unless doing so could cause a person severe gastro-intestinal discomfort.
UPDATE (Sept 5 2019): It should be noted that a recent (2018) study found that a glucose-based hydrogen and methane breath test does not detect bacterial overgrowth in the jejunum, but that a positive breath test may indicate altered jejunal function and microbial dysbiosis. This calls into question the validity of using breath tests in diagnosing SIBO. (Sundin OH, Medoza-Ladd A, Morales E et al, Does a glucose”based hydrogen and methane breath test detect bacterial overgrowth in the jejunum, Neurogastroenterology & Motility 30 (11), https://doi.org/10.1111/nmo.13350).
Positive Breath Test for Methane
As mentioned above, whether a breath test is positive for hydrogen or methane indicates something about the types of bacteria involved in SIBO. In several studies, positive methane results on breath tests have been associated with symptoms of constipation [9-12] and are 5 times more likely to have constipation than those with hydrogen dominant overgrowth [12] and the severity of constipation was found to be directly related to the level of methane [9]. Identifying whether SIBO is methane-predominant is important because the methane-producing bacteria Methanobrevibacter smithii is resistant to many antibiotics [7].
Distinguishing SIBO from IBS
As mentioned in the first article in this series on SIBO (available here) many of the symptoms of Irritable Bowel Syndrome (IBS) and SIBO are similar, including abdominal pain, bloating, gas, bouts of diarrhea or constipation or alternating diarrhea and constipation.
To make matters more confusing, Pimentel et al found that almost 80% (78%) of subjects in their study that had an abnormal lactulose breath test which suggested they had SIBO also met the Rome I criteria for IBS [5]. This begs the question how many of those who have been diagnosed with IBS based on the current Rome IV criteria [13] might actually meet the criteria for SIBO?
It is my opinion that someone who has been unsuccessful at resolving their symptoms of IBS using appropriate dietary treatment with the help of a knowledgeable Dietitian would benefit by undergoing glucose or lactulose breath testing to determine if their symptoms may be caused by SIBO.
In the next article, I will cover the main dietary approaches that are used in SIBO treatment, along with antibiotic or studied herbal antimicrobials. I will also cover why some clinicians do NOT change the person’s diet until after antimicrobial treatment has been completed.
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References
- Quigley EMM. The Spectrum of Small Intestinal Bacterial Overgrowth (SIBO), Current Gastroenterology Reports, (2019) 21:3, https://doi.org/10.1007/s11894-019-0671-z
- Dukowicz AC, Lacy BE, Levine GM. Small intestinal bacterial overgrowth: a comprehensive review. Gastroenterol Hepatol (N Y). 2007;3(2):112—122.
- Ghoshal UC How to interpret hydrogen breath tests. J Neurogastroenterol Motil. 2011; 17: 312—317
- Levitt MD, Furne JK, Kuskowski M, Ruddy J. Stability of human methanogenic flora over 35 years and a review of insights obtained from breath methane measurements. Clin Gastroenterol Hepatol. 2006;4:123—129.
- Pimentel M, Chow EJ, Lin HC, Eradication of small intestinal bacterial overgrowth reduces symptoms of irritable bowel syndrome.
Am J Gastroenterol. 2000 Dec; 95(12):3503-6
- Ghoshal UC, Ghoshal U, Ayyagari A, et al. Tropical sprue is associated with contamination of small bowel with aerobic bacteria and reversible prolongation of orocecal transit time. J Gastroenterol Hepatol. 2003;18:540—547
- 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; doi: 10.1038/ajg.2017.46
- Scarlata K, Small Intestinal Bacterial Overgrowth (SIBO) blog article, January 22, 2014, https://blog.katescarlata.com/2014/01/22/small-intestinal-bacterial-overgrowth/
- Chatterjee S , Park S , Low K et al. Th e degree of breath methane production in IBS correlates with the severity of constipation . Am J Gastroenterol 2007 ; 102 : 837 — 41.
- Attaluri A , Jackson M , Valestin J et al. Methanogenic fl ora is associated with
altered colonic transit but not stool characteristics in constipation without
IBS . Am J Gastroenterol 2010 ; 105 : 1407 — 11. - Hwang L , Low K , Khoshini R et al. Evaluating breath methane as a diagnostic
test for constipation-predominant IBS . Dig Dis Sci 2010 ; 55 : 398 — 403. - Kunkel D , Basseri RJ , Makhani MD et al. Methane on breath testing is
associated with constipation: a systematic review and meta-analysis .
Dig Dis Sci 2011 ; 56 : 1612 — 8. - Schmulson MJ, Drossman DA. What Is New in Rome IV. J Neurogastroenterol Motil. 2017;23(2):151—163. doi:10.5056/jnm16214
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