Response to Drs. Mishkin

AJG – August, 2001

Reprint requests and correspondence: Manuela Merli, M.D., II Gastroenterologia, Dipartimento Medicina Clinica, Universita` “La Sapienza” di Roma, Viale dell’Universita` 37, 00185 Roma, Italy. Received Mar. 8, 2001; accepted Mar. 16, 2001.

Re: Pimentel et al.—Eradication of Small Intestinal Bacterial Overgrowth Reduces Symptoms of Irritable Bowel Syndrome TO THE EDITOR: The article by Pimentel et al. in the December issue (1) concludes that 78% of irritable bowel syndrome (IBS) patients have evidence of small intestinal bacterial overgrowth (SIBO) and that 48% of subjects whose SIBO was eradicated no longer met the Rome criteria for IBS symptoms. Our experience and data do not support the very high prevalence of SIBO quoted in this article. We conducted multiple hydrogen breath tests on IBS patients, such as lactose, fructose, and sorbitol for symptom management, but also glucose and lactulose challenges for their diagnostic potential (2, 3). Our hypothesis was that although IBS patients have a constellation of symptoms, they have no identifiable organic pathology on routine testing. Therefore, the presence of a positive glucose breath test (GBT) or lactulose hydrogen breath test would indicate SIBO, which should be “pathological.” Our data showed that 28% of 100 consecutive patients with functional dyspepsia/IBS had positive lactulose hydrogen breath tests according to the criteria of Pimentel et al. (1). The bulk of our experience relates to the use of the GBT as an indirect test for SIBO (4) in 350 patients. Thirteen percent were GBT⫹. The prevalence rose to 22.2% and 25.6% in the presence of elevated fasting hydrogen and methane, respectively (high background ⱖ15 ppm on at least three sugar challenges). Twenty-seven of a total of 60 GBT⫹ patients were treated with short courses of antibiotics. Symptomatic improvement and reversal of GBT positive to negative occurred in 92.6% and 74.1%, respectively. In our data, the patients who were GBT⫹ were re-evaluated regarding possible explanations for this indirect evidence of abnormal SIBO. Etiologies such as diabetes mellitus with complications and history of previously treated and untreated GI infections were the most common. In the majority of patients we were able to suggest or hypothesize one of these clinical scenarios, but approximately 20% remained unexplained. These data did not support using GBT to exclude functional dyspepsia/IBS by identifying SIBO. From our study and interpretation of Pimentel’s data, there appears to be a subgroup of IBS patients who have SIBO on indirect testing and would benefit from a course of antibiotics. More patients need to be tested to help define this specific patient population. In the absence of more objective data and lack of a true

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gold standard test of SIBO, we believe that this will be a dynamic field that still needs to be explored. Daniel Mishkin, M.D. Seymour Mishkin, M.D. Department of Internal Medicine Sir Mortimer B. Davis Jewish General Hospital Department of Gastroenterology McGill University Health Center McGill University Montreal, Canada

REFERENCES 1. Pimentel M, Chow EJ, Lin HC. Eradication of small intestinal bacterial overgrowth reduces symptoms of irritable bowel syndrome. Am J Gastroenterol 2000;95:3503– 6. 2. Mishkin D, Sablauskas L, Yalovsky M, Mishkin S. Fructose and sorbitol malabsorption in ambulatory patients with postcibal bloating: Comparison with lactose malabsorption. Dig Dis Sci 1997;42:2591– 8. 3. Mishkin D, Blank D, Yalovsky M, Mishkin S. Significance of a positive glucose breath test in patients under investigation for significant bloating. Can J Gastroenterol 1999;13:B108. 4. Kerlin P, Wong L. Breath hydrogen testing in bacterial overgrowth of the small intestine. Gastroenterology 1988;95:982– 8. Reprint requests and correspondence: Daniel Mishkin, M.D., 4060 St. Catherine Street West #770, Montreal, Quebec, H3Z 2Z3 Canada. Received Feb. 20, 2001; accepted Apr. 23, 2001.

Response to Drs. Mishkin TO THE EDITOR: We appreciate Drs. Daniel and Seymour Mishkin’s interest in our study (1) and their comments corroborating that a subgroup of subjects with functional bowel complaints may have SIBO as defined by breath test. Drs. Mishkin describe their findings that a subgroup of subjects with functional GI disease have unexplainable SIBO based on a glucose hydrogen breath test (2). However, they were surprised by our high prevalence because they found the prevalence to be low. In our study (1) we found SIBO in up to 78% of irritable bowel syndrome (IBS) subjects. There may be a number of reasons for the difference in prevalence. It may be related to the type of carbohydrate used in the breath tests of the two studies. In our study, lactulose rather than glucose was employed. An easily absorbable sugar such as glucose can be expected to be rapidly removed from the intestinal lumen and is therefore available for bacterial fermentation briefly and only if bacterial overgrowth involves the proximal small intestine where glucose is available. In contrast, a poorly absorbable starch such as lactulose can be expected to be available for bacterial fermentation in cases of more distal small intestinal overgrowth. Anecdotally, we have observed that many IBS subjects have a normal glucose breath test, with fol-

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Letters to the Editor

AJG – Vol. 96, No. 8, 2001

low-up lactulose breath test demonstrating a classic pattern for overgrowth. Secondly, Mishkin et al. principally tested subjects with functional dyspepsia. Although a proportion of their subjects also had IBS, we included patients on the basis of their meeting only the criteria for IBS. Because functional dyspepsia represents a heterogeneous collection of conditions including problems such as gastroesophageal reflux disease (3), the prevalence of SIBO in this group of patients may well be lower than that in IBS alone. What is most interesting is that, in addition to Mishkin et al. (1), Galatola et al. (4) report a positive 14C-xylose breath test in up to 56% of subjects with IBS. The difference in prevalence between all three studies (1, 2, 4) could be based on the technique used. However, in our study we took this one step further by demonstrating that normalization of the abnormal breath test finding with antibiotics was associated with symptomatic improvement in IBS. This point is very important in the argument that the breath test findings do indeed represent overgrowth (as opposed to a false positive test result) because clinical outcomes improve and are linked to the abnormality of the test. Mark Pimentel, M.D. Henry C. Lin, M.D. GI Motility Program Department of Medicine Cedars-Sinai Medical Center Burns & Allen Research Institute School of Medicine University of California, Los Angeles Los Angeles, California

REFERENCES 1. Pimentel M, Chow EJ, Lin HC. Eradication of small intestinal bacterial overgrowth reduces symptoms of irritable bowel syndrome. Am J Gastroenterol 2000;95:3503– 6. 2. Mishkin D, Blank D, Yalovsky M, Mishkin S. Significance of a positive glucose breath test in patients under investigation for significant bloating. Can J Gastroenterol 1999;13:B108. 3. Pimentel M, Lin HC. Clinical approach to non-ulcer dyspepsia. In: Rao S, Conklin JL, Johlin FC, et al., eds. Gastrointestinal motility: Tests an problem-oriented approach. New York: Kluwer Academic/Plenum Publishers, 1999. 4. Galatola G, Barlotta A, Ferraris R, et al. Diagnosis of bacterial contamination of the small intestine using the 1 g [14C]xylose breath test in various gastrointestinal diseases. Menerva Gastroenterol Dietol 1991;37:169 –75.

Reprint requests and correspondence: Mark Pimentel, M.D., Cedars-Sinai Medical Center, 8635 West 3rd Street, Suite 770, Los Angeles, CA 90048. Received Apr. 9, 2001; accepted Apr. 23, 2001.

Small Intestinal Bacterial Overgrowth and the Irritable Bowel Syndrome TO THE EDITOR: In a recent issue, Pimentel et al. (1) reported their experience with a 10-g lactulose breath hydrogen test (LBHT) in a cohort of 202 community-referred patients who fulfilled Rome I criteria for irritable bowel syndrome (IBS). A high proportion (78%) were considered to have small intestinal bacterial overgrowth (SIBO) based on LBHT findings of two distinct peaks in breath hydrogen concentrations, with the first increase occurring within 90 min of lactulose ingestion and the absolute change in breath hydrogen levels exceeding 20 ppm. These breath test findings were no longer apparent in 25/47 (53%) patients who returned for follow-up assessment approximately 7–10 days after a 10-day course of oral antibiotics, with this change taken to reflect eradication of SIBO. Nearly 50% of those in whom the follow-up LBHT was interpreted to reflect eradication of SIBO no longer fulfilled criteria for IBS, compared to 18% of those in whom SIBO was considered to be persistent. The authors concluded that SIBO is associated with IBS and that eradication of SIBO eliminates IBS in nearly 50% of cases. Such a phenomenon would be of great clinical relevance. Our concern with these interpretations relates to the use of the LBHT for both diagnosis of SIBO and assessment of whether or not antibiotic treatment has been effective. The reliability of the LBHT for diagnosing SIBO has been questioned in studies in which culture of small intestinal aspirate has been taken as the “gold standard.” Our own study (2) found sensitivity and specificity of only 16.7% and 70.0%, respectively. Pimentel et al. propose the alternative notion that the LBHT should be considered more reliable than culture of small intestinal aspirate for diagnosing SIBO, citing the potential for oral contamination of small intestinal aspirates during collection and a report of greater reproducibility of breath testing relative to intestinal culture (3). Notably, this report was based on the use of xylose, an absorbable substrate, rather than the nonabsorbed lactulose for the breath test, whereas the liberal definition of SIBO employed (viable bacterial count ⬎104 colony-forming units [CFU]/ml) would seem more likely to lead to disparate categorization on serial testing than when more restrictive and conventionally adopted definitions of ⱖ105 CFU/ml or ⬎106 CFU/ml (4) are used. In addition, intestinal aspirates were obtained by a tube positioned by fluoroscopy without any measures apparently being undertaken to minimize the potential for contamination of the sample with oropharyngeal secretions. In our study (2), sampling of small intestinal luminal contents was performed under direct vision using an aseptic technique designed to eliminate this latter problem. The reliability of this approach was suggested by the fact that SIBO was