We found SIBO, only in a small subset of patients with IBS (4%), diagnosed by jejunal cultures, using the definition of
cfu/ml of colonic bacteria. This was not different from controls without gastrointestinal symptoms. However, cultures with
cfu/ml were more frequently seen in patients with IBS than in controls. We could not identify a specific motor pattern predicting SIBO, even though these patients tended to have fewer activity fronts, and signs of enteric dysmotility were more common. These manometric abnormalities were not more common in patients with mildly increased bacterial counts. Moreover, similar proportions of positive LHBT and GHBT were obtained in patients with IBS and controls, regardless of how we defined a positive test. In agreement with some earlier studies,27,28,29
our findings do not confirm a strong association between IBS and SIBO as proposed by others,2,3,4,40
even though the relevance of minor alterations of the bacterial flora in the upper gut is unclear.
To the best of our knowledge, this is the first study evaluating growth of bacteria in the small bowel in a large sample of patients with IBS. A previous small study of the microflora of the proximal jejunum included some patients with IBS (n
7) as part of a mixed patient group with gastrointestinal symptoms suggestive of SIBO. In this study, no major differences were found between patients with IBS and controls, but specific information regarding the patients with IBS was not provided.41
Pimentel et al2,3
have reported on SIBO diagnosed by means of LHBT in 78–84% of patients with IBS. We found SIBO in 4% of patients with IBS, defined as
cfu/ml of colonic bacteria, which is the definition most clearly associated with gastrointestinal symptoms.20,21
The reliability of our findings from the jejunal cultures is supported by the results from the GHBT, for which only 1 of 54 patients had a positive test. Similarly, previous studies using the GHBT and 14
C‐xylose test have failed to show a high prevalence of abnormal tests in IBS.28,29
Our results from the LHBT, using the double‐peak definition, with 15% positive tests in patients are in agreement with Walters et al
who observed positive LHBT in 10% of patients with IBS. The discrepancy between Pimentel et al
findings and ours may partly be due to the use of different assessment methods, definitions and inclusion criteria. We could not measure expiratory methane, which has been reported to be important in constipation‐predominant IBS (23% of our patients). Therefore, the breath tests of possible methane‐producing patients would be interpreted as being normal—that is, false negative. At least in their first study, Pimentel et al2
identified Rome I‐positive patients with IBS using a questionnaire among patients initially referred for LHBT. This could perhaps explain the high prevalence of abnormal tests. Our patients also constitute a selected group of patients, as they were referred to our unit due to symptoms refractory to standard treatment. Based on this selection bias, neither our results nor the results of Pimentel et al3
could be generalised to all patients with IBS. When we applied the criteria for an abnormal LHBT with a single peak H2
within 90 or 180 min, the prevalences of abnormal tests were found to be 35% and 78%, respectively. Also, when using these definitions, we could not, similarly to Walters et al
demonstrate an increased prevalence of positive tests in patients with IBS relative to controls. Supported by one study combining LHBT with scintigraphy, enabling anatomical location of the lactulose bolus,22
this late H2
rise is probably due to physiological variations in transit, reflecting colonic fermentation, and not due to bacteria in the small bowel.30
Abnormal colonic fermentation has been reported in IBS,42
and therapies that modify the gut flora may improve symptoms in some patients.26,27,43
Studies on patients with IBS showing symptom improvement after antibiotic treatment2,3,25
have been used to further support the conclusion that SIBO is a pathophysiological factor in IBS.15
However, an antibiotic‐sensitive pathophysiology in IBS may be explained by alterations of colonic bacterial flora25,27,30
resulting in symptom improvement. In bacterial overgrowth caused by delayed transit, antibiotics produce prompt improvements.44,45
About half of the patients with SIBO in our study reported symptom improvement after antibiotic treatment. Unfortunately, our sample was too small to perform a randomised placebo‐controlled evaluation.
We do not have data on antibiotic use before 2 weeks of the study, or on the last use of antibiotics. The time for recolonisation of the small bowel could possibly be >2 weeks. However, this study was conducted in a setting where antibiotics are not available over‐the‐counter, and Sweden is a low consumer of antibiotics compared with other European countries.46
Moreover, we have no reason to believe that patients with IBS would use more antibiotics than healthy subjects.
It has been argued that direct culture is not sufficient to detect SIBO, as sampling is restricted to one location in the proximal small bowel, missing more distal overgrowth.15
As lactulose is not absorbed in the small bowel, LHBT is supposed to be superior in detecting distal bacterial overgrowth.2,3
However, the clinical relevance of such findings is questionable, as the distal ileum is normally colonised with 105–8
Furthermore, it is a common belief that cultures are often false negative, especially concerning obligate anaerobes,11
and modern molecular identification techniques have identified several unculturable bacteria.47
Our aspirates were not immediately incubated, but even strict anaerobic bacteria are thought to tolerate at least 8 h in an environment that is not depleted of oxygen.48
The aspirates were obtained after a meal and a water‐perfused manometry. The amount of bacteria in the proximal gastrointestinal tract is thought to increase soon after a meal,11
whereas the water‐perfused manometry could instead result in a dilution and a lower count of bacteria. However, none of these explanations are likely to explain the differences seen between patients with IBS and controls.
Few of the cultures were completely negative, possibly indicating contamination with oral flora, which is known to be common.49
The patients tended to have higher counts of bacteria, possibly owing to a slightly impaired ability to rinse the upper bowel of bacteria in IBS, as suggested previously.15,24
In line with this, the patients with culture‐verified SIBO had fewer phase III activities, which is thought to be one of the most important mechanisms in the protection against colonisation by rinsing the bowel.7,8
Most of the patients also had enteric dysmotility, as defined by the criteria in box 1. However, this was also seen in several patients without SIBO, making it impossible to predict the presence of overgrowth just by analysis of the small‐bowel motility patterns. We did not perform a formal correlation analysis between the amount of bacteria and the degree of abnormality of MMC, as this cannot be easily quantified. The duration of our manometry recordings were, for practical reasons, relatively short, possibly diminishing the clinical value of our manometries, and of course a possibility that a longer recording time could have discovered an even larger proportion of patients with motor abnormalities. Moreover, the short duration of our recording also made it impossible to assess the cycle length of the MMC in subjects without or with one phase III activity during the 3 h recording. However, the lack of group differences is unlikely to be explained by this.
Except for impaired motility, failure of the gastric‐acid barrier is also known to predispose to bacterial colonisation in the small bowel.7
No drugs known to affect the gastrointestinal tract were allowed within 48 h before the study. However, prior to this, we did not control for use of proton pump inhibitors or other antacids that could affect the bacterial flora of the intestine.50,51
One might expect the use of these drugs to be more frequent in patients with IBS, considering the high overlap with functional dyspepsia.1
This could be one explanation for alterations in the gut flora in patients with IBS, even though our study did not assess this in detail.
The importance of mildly increased small‐bowel bacteria seen in IBS is unclear. This could just be an epiphenomenon due to altered motility. The bacteria could also be the cause of the observed motility alterations. To some extent, the fact that there were no significant differences in the motility parameters before and after treatment speaks against this. However, only seven patients with SIBO were evaluated, and four patients still fulfilled the criteria for SIBO after treatment. Further studies are needed to better characterise these bacterial alterations in IBS, including possible correlations to symptoms. Altered counts of bacteria could induce a low‐grade inflammation, which also needs to be assessed in further studies looking at both systemic and local inflammatory activity, together with an evaluation of the presence of post‐inflammatory IBS.
In conclusion, using several diagnostic methods including culture of jejunal aspirate and hydrogen breath tests, our results do not support a strong association between IBS and SIBO according to the standard definition. Most patients with high counts of bacteria were found to have minor uncharacteristic motility alterations, which may have been a predisposing factor in these cases. Of interest, but of uncertain relevance, a significant subset of patients with IBS seem to have mildly increased counts of bacteria in the upper gut. This finding, and the correlation with symptoms in IBS, needs to be evaluated in further studies.