Breath testing and antibiotics for possible bacterial overgrowth in irritable bowel syndrome

Keywords::

• antibiotics
• breath testing
• irritable bowel syndrome
• small intestinal bacterial overgrowth

Irritable bowel syndrome (IBS) is a functional disorder of the gastrointestinal tract, with a chronic relapsing and remitting course. The cardinal symptoms that sufferers report are the presence of abdominal pain and/or discomfort in association with a disturbance in their bowel habit [1], but abdominal bloating, the passage of mucus per rectum and tenesmus are also often experienced. IBS is extremely common in the general population, with a prevalence of between 5 and 20% [2], depending on the criteria used to define its presence. There is no known structural cause for the symptoms sufferers report, but proposed mechanisms include abnormal pain processing [3], low-grade inflammation [4], abnormal gastrointestinal motility [5] and perturbations of the intestinal flora [6].

Despite recommendations from national and international guidelines that a diagnosis of IBS should be made on clinical grounds in individuals who meet diagnostic criteria for the condition, without the need for recourse to invasive investigations, this leaves both the patient and the physician with whom they are consulting for their symptoms with a certain degree of uncertainty as to whether the diagnosis of IBS is correct. In addition, some studies have suggested that the prevalence of other organic gastrointestinal conditions, including celiac disease [7], bile salt malabsorption [8] and exocrine pancreatic insufficiency [9], are higher in individuals with symptoms that would otherwise meet criteria for IBS.

Bloating is reported by a significant proportion of IBS patients [10], and some investigators have reported increased hydrogen gas production following the administration of fermentable substrates in subjects with IBS compared with healthy controls [11]. A possible unifying explanation for these observations has been that certain individuals who meet diagnositic criteria for IBS may actually have small intestinal bacterial overgrowth, caused by colonization of the proximal small bowel with fermenting bacteria.

Some researchers have studied the therapeutic effects of nonabsorbable antibiotics, such as rifaximin, in the treatment of IBS. A small, randomized, placebo-controlled trial published in 2006 [12], which used 400 mg of rifaximin three-times daily for 10 days, suggested a greater percentage improvement in global IBS symptom scores and also, in a secondary analysis, for the individual symptom of abdominal bloating. This beneficial effect appeared to persist for up to 10 weeks after therapy had been discontinued. More recently, two randomized controlled trials [13], Target 1 and Target 2, each recruiting over 600 participants with IBS, have been published in abstract form. Subjects were randomized to receive either 550 mg of rifaximin three-times daily or placebo for 2 weeks. Both of these trials reported a statistically significantly higher rate of adequate relief of global IBS symptoms with rifaximin up to 4 weeks after the cessation of therapy, approximately 40% with active therapy compared with rates of around 30% in those allocated to placebo. Rates of adequate relief of bloating were also of a similar magnitude with rifaximin.

These data suggest that screening individuals with symptoms suggestive of IBS for small intestinal bacterial overgrowth, in order to identify individuals who are likely to benefit the most from antibiotic therapy, may be a worthwhile strategy. Noninvasive screening for bacterial contamination of the small bowel using hydrogen breath testing has been conducted by several groups of researchers. Unfortunately, however, the results of such studies are conflicting, with some investigators reporting that a positive breath test is more common in individuals with IBS compared with healthy asymptomatic subjects [14], and others reporting that there is no increase in prevalence of a positive test [15]. Two systematic reviews and meta-analyses have been published recently that examine the issue in detail [16,17]; however, these studies also came to different conclusions. The earlier study [17], published in late 2009, identified five case–control studies that used lactulose, glucose or sucrose hydrogen breath testing in adults meeting diagnostic criteria for IBS, and reported that the odds of a positive test was generally higher in individuals with IBS, but that the magnitude of this observation varied according to the threshold used to define a positive test, and noted that there was a large amount of heterogeneity between studies, suggesting that combining their results may not be appropriate. The second study identified 11 case–control studies, although some of these were excluded from the prior meta-analysis on the basis of inadequate sample size, and two were conducted in children [16]. The authors reported greater than fourfold odds of a positive test in individuals with suspected IBS compared with that of healthy controls.

There are several caveats to the application of these data to routine clinical practice. First, breath tests themselves are not accurate in all situations. Depending on the substrate used there is the potential, in some instances, for it to be rapidly absorbed in the proximal small intestine, leading to a false-negative result and thereby reducing sensitivity. It is also difficult to discriminate between a truly positive result and a rise in breath hydrogen caused by rapid intestinal transit, limiting specificity. Second, there is a lack of consensus as to what threshold should be used to define a positive test. Third, the gold standard for the diagnosis of small intestinal bacterial overgrowth remains jejunal aspirate and culture. To date, only one case–control study has used this technique [18], and this failed to demonstrate a significant difference in the prevalence of bacterial overgrowth in cases with suspected IBS compared with controls. However, whether this should be viewed as the gold standard at all is controversial, with concerns that contamination of the distal small intestine is not detected by this method, and that there are species of bacteria that are, as yet, not able to be cultivated using conventional culture-based techniques. Finally, a group of investigators has proposed that one unifying explanation for the high rates of positive hydrogen breath tests in individuals with IBS could be concurrent use of proton pump inhibitors [19], given empirically by physicians to many patients with gastrointestinal symptoms. Unfortunately, as few of the studies included in these meta-analyses have either reported the prevalence of the use of these drugs, or excluded individuals using them, whether this is a potential confounding factor remains unclear.

In summary, there is some evidence to suggest that there are disturbances of small intestinal flora following hydrogen breath testing in adults with symptoms that meet diagnostic criteria for IBS, and that nonabsorbable antibiotics, such as rifaximin, are more effective than placebo in the treatment of the condition; however, whether the former observation is due to causation or confounding by another factor, and the latter partly due to the known high placebo response to therapy in IBS [20] remains unclear.

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.