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Small intestinal bacterial overgrowth (SIBO) is a condition characterised by abnormally high bacterial counts in the small intestine, typically defined as exceeding 105 organisms/mL.1, 2 SIBO is commonly present in several conditions including those with gastrointestinal dysmotility or altered or impaired gut barrier, such as achlorhydria, scleroderma, coeliac disease, pancreatitis or altered anatomy.3, 4 Clinically, SIBO is typically considered a malabsorption syndrome, although the manifestations may vary in different individuals.5–7 This variability in clinical presentation is likely induced by many factors including underlying medical conditions, the extent of involved intestinal tract and the bacterial species involved. The most common symptoms include abdominal pain, bloating, diarrhoea, steatorrhoea and flatulence.1 SIBO symptoms are also similar to those observed in patients affected by irritable bowel syndrome (IBS). Recently several investigators have linked SIBO and IBS and have proposed a role for SIBO in the causation of IBS.8, 9 Prevalence rates of SIBO in IBS patients have been reported to be in the range of 31–84%8–11 based on hydrogen breath tests. However, others have argued that PPI use may contribute to the link between SIBO and IBS12 and much controversy remains. Nonetheless, most of the recent literature regarding SIBO has focused on its role in IBS pathophysiology with little updated information about SIBO itself.
Diagnostic tests for SIBO are imperfect, leading to greater ambiguity regarding the role of SIBO in causing common gastrointestinal symptoms.13 The diagnostic tools for SIBO include indirect tests (such as the C-xylose test and hydrogen-methane breath tests using lactulose or glucose) or direct aspiration with culture of small bowel contents.13–15 Whereas non-invasive carbohydrate-based breath testing is widely being used to diagnose SIBO, the test has inherent problems. The main limitation is that abnormal gastrointestinal transit cannot be excluded; in patients with rapid transit, lactulose may produce an early peak of hydrogen which may be falsely interpreted as SIBO.16 In addition, hydrogen testing may fail to detect overgrowth of nonhydrogen producing bacteria that are methane producers,13, 17 although this is less of an issue as tests measuring both gases are increasingly available. The clinical utility of breath tests has been questioned due to these issues as well as its low sensitivity and specificity in comparison with culture of small bowel aspirate culture.2, 18 Small bowel aspirate culture is still considered the gold standard in the diagnosis of SIBO, although it is invasive, expensive, requires microbiology facilities to perform testing, takes several days to obtain a result and samples only the proximal small intestine.
Although quantitative culture of small intestinal secretions is the gold standard diagnostic test for SIBO, little is known about its overall clinical yield in the current clinical practice. Symptoms of loose stool, bloating and dyspepsia are not only common, but also importantly, not specific to SIBO or even IBS. The aim of our study was to assess the overall yield of duodenal culture in patients referred for this test in an open access, high-volume endoscopy centre at a major academic centre, and to identify the clinical characteristics predictive of a positive duodenal aspirate culture. Our goal was to identify the symptoms, diagnoses and medications that are associated with SIBO in modern day practice. Thus, we identified all patients undergoing quantitative duodenal aspirate culture in a 1-year period and performed a medical chart review to collect clinical information to accomplish our aims.
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In this study, we observed that the proportion of individuals with an abnormally elevated bacterial count from small bowel aspirates collected in individuals referred for suspicion of bacterial overgrowth was low – 8% overall. By logistic regression, the main clinical characteristics associated with SIBO were: older age, history of abdominal surgery, inflammatory bowel disease, pancreatitis, small bowel diverticula, steatorrhoea and narcotic use. Among the small number of patients with inflammatory bowel disease, pancreatitis and small bowel diverticula, the prevalence of SIBO ranged from 16% to 50%.
Age may be a predisposing factor in the development of small intestinal bacterial overgrowth.20–22 MacMahon et al.21 studied 30 randomly selected elderly patients between 68 and 90 years of age admitted at a tertiary hospital for assessing the association between age and small intestinal bacterial overgrowth by duodenal aspirate. They observed that 20 of the 30 small bowel aspirates had proven SIBO, and advancing age significantly correlated with rising counts of small bowel anaerobes count. Similarly, we found that advancing age was a very strong predictor for an abnormal or indeterminate duodenal aspirate compared with negative cultures. Presumably the elderly are more likely to have risk factors for bacterial overgrowth, such as a reduction in intestinal motility, small bowel diverticulosis, intestinal surgery and achlorhydria as well as higher medication use.20–22
Although in a recent systematic review summarising diagnostic testing for SIBO, Khoshini et al.13 suggested that no test was ideal for assessing small bowel intestinal bacterial overgrowth, small bowel culture with bacterial counts of more than 105 cfu/mL is still currently considered the gold standard for diagnosing SIBO.2, 17, 23 Our study also used this definition for evaluating SIBO in various clinical settings, along with lower anaerobic bacterial counts (more than 104 cfu/mL) As expected, we found that abnormal small bowel bacteria cultures were present in several diseases which are highly likely to induce stagnation in the small bowel, such as Crohn’s disease, pancreatitis, or small bowel diverticula. These results are highly consistent with previous studies by Pimentel et al.24 demonstrating abnormal lactulose breath testing in patients with inflammatory bowel disease, by Trespi and Ferrieri4 showing abnormal hydrogen breath test in patients with chronic pancreatitis, and by others13, 25 revealing SIBO in patients after intestinal surgery. Furthermore, SIBO after GI surgery or small bowel diverticulosis treated with antibiotics, including norfloxacin, amoxicillin, tetracycline or metronidazole, led to significant symptom improvement.26–28 We also observed an association between SIBO and use of narcotics. Narcotics disrupt intestinal motility and result in delayed intestinal transit, which can then predispose towards bacterial overgrowth in the small bowel. This finding may have broader clinical implications for health care providers caring for those with chronic pain.
The relationship between SIBO and IBS continues to be hotly debated in the literature.10 Among our patients with IBS, the prevalence of SIBO by quantitative duodenal aspirate culture was only 2%, and an additional 6% had an abnormal aspirate. Both figures were less than those in patients without IBS. Thus, IBS was not found to be a predictor of excess bacteria in small bowel aspirates in our sample of patients being referred for endoscopic aspirate culture. Our findings based on duodenal aspirate culture show quite a contrast in findings as proposed by others based on hydrogen breath testing8, 29 and response to antibiotic therapy such as rifaxamin.30 The discrepancy between our studies and the studies using indirect studies could be due to differences in study populations or differences in test sensitivity. Our IBS patient sample differs from other studies and the general IBS patient population in that our patients were not a consecutive group of IBS patients. Rather, they were a selective group of patients being seen at a major medical centre whose physicians were concerned enough about their symptoms to be referred for testing. In our selected IBS group, the prevalence of SIBO was still low. Our results are more consistent with a previous study by Posserud et al. which also used small bowel aspirate culture as the diagnostic test for SIBO.23 They too observed a low prevalence of SIBO – 4% in patients with IBS and 4% among controls – and they failed to show a significant difference in the prevalence of SIBO in cases meeting diagnostic criteria for IBS compared with healthy asymptomatic controls from the general population. This suggests that the low frequency of SIBO that we observed is due to differences in test sensitivity between direct and indirect testing.
The lack of association between PPI use and SIBO bears further discussion. PPI use in our sample was quite common – over one-third of the sample were taking PPIs. We observed that patients with PPI use, more commonly had an abnormal duodenal aspirate culture (10%) result compared to subjects without PPI use, but we did not find a significant association between PPI use and SIBO (P > 0.05). Many studies31–34 have demonstrated that hypochlorhydria is a risk factor for SIBO. Thorens et al.31 showed that the incidence of gastric and duodenal bacterial overgrowth is considerably higher in patients treated with omeprazole compared with cimetidine (53% vs. 17%). Furthermore, Lewis et al.33 showed that omeprazole was associated with SIBO as well as with shorter intestinal transit times. Nonetheless, we did observe a significant association between PPI use and an increased odds for indeterminate culture results (vs. a negative result, OR = 3.0, 95% CI: 1.7–5.1) in which bacteria was present in the duodenum, but at insufficient quantities to be consistent with SIBO. It is possible that PPI use may predispose an individual to low-grade or mild SIBO, but the relevance of a moderate amount of bacteria still remains to be determined. Similar observations were seen in our IBS patients. That is, the proportion of IBS patients with abnormal culture results consistent with SIBO or with an intermediate number of bacteria was low among IBS patients not taking a PPI. Among IBS patients taking a PPI, those with ‘true’ SIBO were few (2%), but the number with the intermediate number of bacteria was four-fold higher relative to those with negative cultures (P < 0.05). Thus, it is possible that PPI use explains the link between SIBO – albeit a low grade form – and IBS as proposed by Spiegel et al.12
Our study has some important limitations. First of all, our study was based on a retrospective medical chart review of patients referred for upper endoscopy in a tertiary centre. The prevalence of GI disorders including IBS from a medical record review may represent underestimates owing to the varying quality of information in the medical record entries. In addition, the role of referral bias cannot be completely negated. It is conceivable that IBS patients seen at our academic centre are likely to be more severe than IBS in the general population; hence, if any relationship of IBS with SIBO existed, our study should have been more likely to see it, but our study failed to show a positive association. Our study had to rely on a physicians’ clinical diagnosis of IBS and could not apply the Rome diagnostic criteria; hence, the IBS cohort may have been more heterogeneous than if the Rome criteria had been applied. The number of patients with constipation was also low, and thus, the role of SIBO in IBS-C cannot be evaluated here. Our study used proximal duodenal cultures collected of upper endoscopy too; it is conceivable that bacterial overgrowth of the distal small intestine was missed. It is also worth noting that an additional 9% of the sample who were referred for small bowel aspirates fell into the ‘indeterminate’ range with evidence of some bacteria in the duodenum, the clinical relevance of which is not yet known but perhaps should be studied in greater detail. It is also important to point out that although some readers want to know whether SIBO by culture is more common among IBS patients or PPI users (or another trait) compared with healthy controls, our comparison group consisted of other individuals with symptoms and as such, our study can only report whether these traits were predictive of SIBO among symptomatic patients. The limitations not withstanding, our large patient volume undergoing duodenal aspirate collection provided a unique opportunity to evaluate multiple clinical features and potential risk factors for SIBO.
We conclude from this retrospective study that SIBO is unlikely to be associated with IBS based on quantitative duodenal bacterial cultures, including anaerobic bacterial cultures. We can also conclude that steatorrhoea – albeit an uncommon symptom – is the most specific and predictive of an abnormal culture result. SIBO is clearly linked to older age, previous gastric and intestinal surgery, narcotic use, inflammatory bowel disease, pancreatitis and small bowel diverticula in modern clinical practice, and providers of patients with these characteristics should consider SIBO as a cause of worsening gastrointestinal symptoms.