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Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgement
  8. References

Aliment Pharmacol Ther 2011; 33: 1059–1067

Summary

Background  There has been increasing interest in small intestinal bacterial overgrowth (SIBO) after reports of a link with irritable bowel syndrome (IBS), yet our understanding of this entity is limited.

Aim  Our aim was to estimate the yield of patients undergoing duodenal aspirate culture, and to identify symptoms and features that predict SIBO.

Methods  A medical chart review of patients who had undergone duodenal aspirate culture at an academic medical centre in 2003 was performed to record clinical characteristics and culture results. The associations between aspirate results and symptoms, medical diagnoses and medication use were assessed using logistic regression.

Results  A total of 675 patients had available aspirate results. Mean age of the sample was 53 (s.d. 17) and 443 (66%) were female patients. Overall, 8% of aspirates were positive for SIBO; 2% of IBS patients had SIBO. Older age, steatorrhoea and narcotic use were associated with SIBO (P < 0.05). PPI use was not associated with SIBO, but was associated with bacterial growth not meeting criteria for SIBO (P < 0.05). Inflammatory bowel disease (IBD), small bowel diverticula and pancreatitis were positively associated with an abnormal duodenal aspirate (P < 0.05), but other conditions including IBS were not associated with SIBO.

Conclusion  Older age, steatorrhoea, narcotic use, IBD, small bowel diverticula and pancreatitis were associated with small intestinal bacterial overgrowth based on abnormal duodenal aspirate culture results. However, no clear associations of true small intestinal bacterial overgrowth with IBS or PPI use were detected, in contrast to recent speculation.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgement
  8. References

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.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgement
  8. References

Study design

This retrospective chart review examined the medical records of all patients who had undergone a duodenal aspirate and culture at Mayo Clinic in Rochester, MN, between 1 January and 31 December 2003. Specifically, among all 7454 patients who underwent esophagogastroduodenoscopy (EGD), 699 patients who had a duodenal aspirate and culture were identified via an endoscopy database system. Nine patients who refused general authorisation for review of their medical records for research per Minnesota statute (section 144.295) were excluded. The study was approved by the Mayo Clinic Institutional Review Board (IRB).

Data collection

Demographic data as well as clinical data were collected from complete medical records, including all in-patient and out-patient visits. Variables were obtained from review of the physicians’ notes, including symptoms, current and recent medication use, and medical and surgical history. Culture test results were obtained from laboratory reports. The final diagnosis of each patient given by their primary physician was recorded and was confirmed by the study team member (KCR) based on the history, general medical examination and all laboratory tests.

An abnormal duodenal aspirate was defined as intestinal aerobic bacterial counts of more than 100 000 cfu/mL (colony forming units/millilitre)10, 13 or intestinal anaerobic bacterial counts of more than 10 000 cfu/mL.13, 19 Indeterminate culture results were defined by any bacterial growth of aerobic bacteria counts between more than 0 and less than 100 000 cfu/mL, or anaerobic bacterial counts between more than 0 and less than 10 000 cfu/mL. A negative aspirate culture result was defined as a bacterial count of 0 cfu/mL for either aerobic or anaerobic counts.

Statistical analysis

The proportion of positive aspirate results was estimated in patients overall as well as by individual gastrointestinal diagnoses. The odds ratios (OR) and 95% confidence intervals for a positive aspirate vs. negative, intermediate vs. negative and positive vs. intermediate aspirate result were estimated for specific clinical factors using logistic regression models (generalised logit link function) adjusting for age and gender. Descriptive statistics for variables are reported by the three aspirate result categories, significance test reported is the global P-value from the logistic regression model. A P-value of <0.05 was considered statistically significant. All analyses utilised the sas statistical analysis package (SAS Institute Inc., Cary, NC, USA).

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgement
  8. References

Patient demographic characteristics

During the year audited, a total of 690 patients had duodenal aspirates sent for culture at our institution. The mean age of the patients was 53 (± s.d. 17 years); 453 (66%) were female patients. The primary indications for the aspirates given by the patients’ primary physicians are shown in Figure 1. The most common indication for a duodenal aspirate was diarrhoea (42%), followed by weight loss (36%), dyspepsia (35%) and abdominal pain (33%). Less common indications for testing included IBS (9%) and malabsorption (8%). There were 675 patients in whom the aspirate result was known, and only these patients were included in the analyses.

image

Figure 1.  Indication given for collection of aspirates by patients' physicians.

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IBS was the most common diagnosis in this sample, with 148 (22%) being given a diagnosis of IBS by their physicians. The 148 subjects with IBS had a mean age of 49 (± s.d. = 17 years) and 114 (77%) were female patients. By chart review, 46% reported more than three bowel movements a day to their physicians, 3% reported less than three bowel movements per week, 9% alternated, and 16% had bowel frequency between 2/week to 3/day, with bowel habit frequency being unknown in 26%. The distribution for duration of symptoms was 20% less than 1 year, 28% 1–3 years, 24% 4–10 years, 19% exceeding 10 years, with duration unknown in 9%. Among the 148, 26% were documented to be taking an antispasmodic and 16% were taking a laxative. Overall, 36% of the IBS patients were documented to be using PPIs and 18% were taking a narcotic during the period of study.

Quantitative duodenal aspirate culture yield

The results of the duodenal aspirate culture are shown in Table 1. Among 675 subjects, 54 patients (8%) had abnormal duodenal aspirates, 62 patients (9%) had indeterminate duodenal aspirates, while the vast majority (83%) of those undergoing culture were negative. Among the 54 patients with abnormal duodenal aspirates, 45 (7%) patients had aerobic bacteria counts more than 100 000 cfu/mL, 2 (0.3%) patients had anaerobic bacteria counts more than 10 000 cfu/mL, and 7 (1%) patients had both abnormal aerobic and anaerobic bacterial counts.

Table 1.   Results of duodenal aspirate culture
 Culture results of duodenal aspirate N = 675 (%)
Negative aspirate culture559 (83%)
Indeterminate duodenal aspirate (total)62 (9%)
 0 < Aerobic Gram-negative bacillus <100 000 cfu/mL62 (9)
 0 < Anaerobic bacteria <10 000 cfu/mL0 (0)
Abnormal duodenal aspirate (total)54 (8%)
 Aerobic gram-negative bacillus ≥100 000 cfu/mL45 (7)
 Anaerobic bacteria ≥10 000 cfu/mL2 (0.3)
 Aerobic gram-negative bacillus ≥100 000 and anaerobic bacteria ≥10 000 cfu/mL7 (1)

Association with demographic and medical characteristics

The demographic features of the subjects with negative, indeterminate and abnormal duodenal aspirates are presented in Table 2. Age was associated with aspirate result (P < 0.01); those with abnormal duodenal aspirates were older than those with a negative culture and those with an indeterminate result. Subjects with SIBO had a mean age of 66 (± 13 years) and 65% were female patients, while those with indeterminate duodenal aspirate had a mean age of 58 (± 16 years) and 56% were female patients. Gender, race and smoking were not significantly associated with aspirate results. A history of abdominal surgery, such as gastric and intestinal surgery, was associated with aspirate result (P < 0.01), being more commonly observed in those with abnormal duodenal aspirates compared to subjects with negative aspirates.

Table 2.   Demographic characteristics and clinical diagnoses of subjects with negative and abnormal duodenal aspirates
Characteristic/Diagnosis (n = number with data)Negative Aspirate† N = 559Indeterminate Aspirate† N = 62Abnormal Aspirate† N = 54Overall† N = 675
  1. P < 0.05 for overall association with aspirate result.

  2. † The column percentages are based on the corresponding nonmissing values for each characteristic/diagnosis.

Age (n = 675), mean (± s.d.)*51 ± 1658 ± 1666 ± 1353 ± 17
Gender (n = 675), n (% female)373 (67)35 (56)35 (65)443 (66)
Race (n = 534), n (% Caucasian)412 (93)44 (90)37 (88)493 (92)
Smoking (n = 650), n (% current smoker)105 (19)11 (18)9 (18)125 (19)
History of any abdominal surgery, (n = 675)*306 (55%)46 (74%)45 (83%)397 (59%)
 Gastric surgery (n = 675), n (% yes)41 (7)10 (16)14 (26)65 (10)
 Intestinal surgery (n = 674), n (% yes)61 (11)19 (31)14 (26)94 (14)
 Other abdominal surgery (n = 675), n (% yes)272 (49)36 (58)33 (61)341 (51)
Clinical diagnosis
 Irritable bowel syndrome (n = 665), n (% yes)134 (24)11 (18)3 (6)148 (22)
 Inflammatory bowel disease (n = 671), n (% yes)*46 (8)3 (5)9 (17)58 (9)
 Coeliac disease (n = 672), n (% yes)46 (8)4 (6)1 (2)51 (8)
 Lactose intolerance (n = 673), n (% yes)19 (3)2 (3)1 (2)22 (3)
 Cirrhosis (n = 674), n (% yes)12 (2)2 (3)3 (6)17 (3)
 Pancreatitis (n = 673), n (% yes)*18 (3)3 (5)6 (12)27 (4)
 Colon cancer (n = 675), n (% yes)10 (2)1 (2)1 (2)12 (2)
 Short bowel syndrome (n = 673), n (% yes)5 (1)0 (0)3 (6)8 (1)
 Small bowel diverticula (n = 673), n (% yes)*4 (1)1 (2)5 (9)10 (1)
 Diabetes mellitus (n = 669), n (% yes)65 (12)13 (21)6 (12)84 (13)

Of the 148 patients with an IBS diagnosis, 3 (2%) had findings consistent with SIBO while in those without a diagnosis of IBS (N = 517), the proportion with findings consistent with SIBO was 10%. Conversely, of those with an abnormal aspirate result suggestive of SIBO, only 6% had an IBS diagnosis whereas among those with negative aspirate results, 24% had an IBS diagnosis (Table 2). Certain diseases were associated with aspirate status including inflammatory bowel disease (P = 0.024), pancreatitis (P = 0.016) and small bowel diverticula (P = 0.016), which were more commonly present in those with abnormal aspirates compared with other groups.

Gastrointestinal symptoms and medications

The specific gastrointestinal symptoms for these 675 subjects subdivided by their aspirate results are shown in Table 3. Among patients with steatorrhoea (N = 21), six (29%) had an abnormal aspirate result while in those without steatorrhoea (N = 650), the proportion with an abnormal aspirate result was 7%. Conversely, steatorrhoea was the only sign or symptom that was more common in those with an abnormal duodenal aspirate (11%) compared with the other two groups. None of the other gastrointestinal symptoms were significantly associated with an abnormal duodenal aspirate. Specifically, abdominal pain, diarrhoea and bloating were not more common in those with SIBO.

Table 3.   Gastrointestinal symptoms and medication use in subjects with negative, indeterminate and abnormal duodenal aspirates
Symptom/Medication (n = number with data)Negative aspirate† N = 559Indeterminate aspirate† N = 62Abnormal aspirate† N = 54Overall† N = 675
  1. P < 0.05 for overall association with aspirate result.

  2. † The column percentages are based on the corresponding nonmissing values for each symptom/medication.

Symptoms
 Abdominal pain (n = 490), n (% yes)325 (81)40 (83)30 (73)395 (81)
 Bloating/distension (n = 316), n (% yes)188 (73)17 (61)23 (72)228 (72)
 Diarrhoea (n = 672), n (% yes)403 (72)45 (73)39 (74)487 (72)
 Steatorrhoea (n = 671), n (% yes)*13 (2)2 (3)6 (11)21 (3)
 Faecal incontinence (n = 199), n (% yes)95 (59)18 (82)12 (71)125 (63)
 Mucus in stools (n = 156), n (% yes)59 (44)2 (20)4 (33)65 (42)
 Incomplete evacuation (n = 87), n (% yes)26 (42)4 (57)3 (38)33 (43)
 Weight loss >7 lbs within 6 months (n = 672), n (% yes)211 (38)26 (42)27 (51)264 (39)
Medication
 PPI (n = 670), n (% yes)187 (34)37 (61)25 (48)249 (37)
 H2 blocker (n = 668), n (% yes)43 (8)4 (7)1 (2)48 (7)
 Antacids (n = 670), n (% yes)28 (5)3 (5)5 (10)36 (5)
 Narcotics (n = 671), n (% yes)*103 (18)12 (20)17 (32)132 (20)
 Antispasmodic (n = 669), n (% yes)100 (18)8 (13)10 (19)118 (18)
 Antibiotic (within last 3 months) (n = 672), n (% yes)71 (13)5 (8)8 (15)84 (13)
 Laxative (n = 641), n (% yes)56 (10)7 (12)3 (6)66 (10)

The frequency of medication use, including proton pump inhibitor (PPI), histamine-2 antagonists, over-the-counter antacids, laxatives, antispasmodics and narcotics in subjects with negative, indeterminate, or abnormal duodenal aspirates is shown in Table 3. In patients taking a PPI (N = 249), the proportion of those with an abnormal aspirate result was 10% while in those not on a PPI (N = 421) the proportion with an abnormal result was 6%, however, this association was not statistically significant. Conversely, among those with an abnormal aspirate result, 48% were taking a proton pump inhibitor (PPI) while among those with a negative aspirate result, 34% were taking a PPI. Narcotic use was associated with aspirate result (P = 0.014) with 13% having an abnormal aspirate result in patients using narcotics compared to 7% in those not using narcotics. Conversely, narcotic use was more common in those with an abnormal duodenal aspirate vs. the other groups with nearly one-third of those having an abnormal aspirate result taking narcotics, compared with 18% of those with negative results.

Other medication usage was not significantly associated with aspirate result status.

Odds ratios for aspirate culture results associated with specific clinical characteristics

The odds ratios (ORs) for aspirate status (positive vs. negative, indeterminate vs. negative and positive vs. indeterminate) corresponding to each demographic, medical and clinical characteristic are summarised in Table 4. Each 5-year age increment increased the odds for an abnormal culture result, and age greater than 50 years (relative to <50) had an OR of 5.7 (95% CI: 3.7–23.4) for SIBO vs. a completely negative culture result. Prior abdominal surgery (relative to none) was associated with a three-fold increased odds (OR = 3.2, 95% CI: 1.5–6.9) for an abnormal culture result over a negative result. Notably an IBS diagnosis was inversely associated with an abnormal aspirate result with an OR = 0.2 (95% CI: 0.1–0.7) for an abnormal result in those with IBS relative to those without. An IBD diagnosis was associated with a three-fold increased odds for SIBO; pancreatitis nearly a five-fold increased odds; and small bowel diverticula over a seven-fold increased odds for SIBO.

Table 4.   Odds ratio (95% CI) for aspirate status and clinical characteristics
 Abnormal aspirate relative to negativeIndeterminate relative to negativeAbnormal aspirate relative to indeterminate
  1. Values in bold denote statistical significance (P < 0.05).

  2. * Univariate model, for all other variables the models included age and gender.

Age, per 5 years*1.4 (1.2–1.5)1.1 (1.05–1.2)1.2 (1.1–1.4)
Age >50 years*5.7 (3.723.4)2.3 (1.3–4.0)2.5 (1.01–6.4)
Gender, Female*0.9 (0.5–1.6)0.6 (0.4–1.1)1.4 (0.7–3.0)
Any previous abdominal surgery3.2 (1.5–6.9)2.3 (1.2–4.2)1.4 (0.6–3.6)
 Previous gastric surgery4.9 (2.3–10)2.5 (1.2–5.3)1.9 (0.8–4.9)
 Previous intestinal surgery2.0 (0.97–3.9)3.2 (1.76.0)0.6 (0.3–1.4)
 Previous other abdominal surgery1.5 (0.9–2.8)1.5 (0.8–2.5)1.1 (0.5–2.3)
Clinical diagnosis
 IBS0.2 (0.1–0.7)0.8 (0.4–1.6)0.3 (0.1–1.1)
 IBD3.0 (1.3–6.8)0.6 (0.2–2.1)4.6 (1.2–18)
 Pancreatitis4.6 (1.6–13)1.5 (0.4–5.4)3.0 (0.7–13)
 Small bowel diverticula7.4 (1.8–30)1.5 (0.2–14)4.9 (0.5–44)
Symptoms
 Abdominal pain0.9 (0.4–1.9)1.5 (0.7–3.4)0.6 (0.2–1.6)
 Bloating/distention1.0 (0.4–2.3)0.5 (0.2–1.2)1.8 (0.6–5.3)
 Diarrhoea1.0 (0.5–2.0)1.0 (0.5–1.8)1.0 (0.5–2.4)
 Urgency0.3 (0.1–1.01)4.7 (0.6–37)0.1 (0.01–0.6)
 Steatorrhoea4.1 (1.4–12)1.2 (0.3–5.4)3.5 (0.7–18)
 Faecal incontinence1.1 (0.4–3.6)2.3 (0.7–7.5)0.5 (0.1–2.2)
 Mucus in stools0.7 (0.2–2.5)0.3 (0.1–1.7)2.1 (0.3–15)
 Incomplete evacuation0.9 (0.2–4.4)2.1 (0.4–11)0.4 (0.1–3.5)
Medication
 PPI1.7 (0.96–3.2)3.0 (1.7–5.1)0.6 (0.3–1.3)
 H2 blocker0.2 (0.02–1.4)0.8 (0.3–2.3)0.2 (0.03–2.1)
 Antacids1.6 (0.6–4.6)0.9 (0.3–3.0)1.8 (0.4–8.2)
 Narcotics2.7 (1.4–5.2)1.2 (0.6–2.4)2.2 (0.9–5.2)
 Antispasmodic0.9 (0.4–1.8)0.6 (0.3–1.4)1.4 (0.5–3.8)
 Antibiotic (within last 3 months)1.3 (0.6–2.9)0.6 (0.2–1.6)2.1 (0.6–6.9)
 Laxative0.4 (0.1–1.5)1.1 (0.5–2.5)0.4 (0.1–1.7)

Considering individual symptoms, steatorrhoea was positively associated with an abnormal aspirate compared to a negative aspirate result with an OR = 4.1 (95% CI: 1.4–12.0). Use of narcotics was associated with a significant OR of 2.7 (95% CI: 1.4–5.2) for abnormal aspirate results compared to a negative result (OR = 3.0, 95% CI: 1.7–5.1). Similar findings regarding PPI use was seen among the 148 IBS patients. Among IBS patients not taking a PPI, the proportion with SIBO or an indeterminate culture result was rare – 2% and 3%, respectively. Among IBS patients taking a PPI, the proportion with SIBO was still low (2%) but the proportion with an indeterminate culture result was higher at 15%. Thus, an analysis incorporating combinations of IBS status and PPI use indicated that in IBS subjects, PPI use was not a risk factor for an abnormal aspirate result consistent with SIBO compared to negative culture results (OR = 0.9, 95% CI: 0.1–102.2, P = 0.91), but was a risk factor for an indeterminate culture result compared to those with negative culture results (OR = 4.7, 95% CI: 1.2–18.7, P = 0.03). However, the odds for specific aspirate culture results in those using PPIs (relative to those not using PPIs) did not differ significantly (P = 0.65) between IBS patients and non-IBS patients. Specifically, in non-IBS subjects, PPI use modestly increased the odds for an abnormal aspirate result consistent with SIBO compared to negative culture results (OR = 1.8, 95% CI: 0.9–3.3, P = 0.07), but again was a risk factor for an indeterminate culture result compared to those with negative culture results (OR = 2.7, 95% CI: 1.4–4.9, P < 0.01).

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgement
  8. References

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.

Acknowledgement

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgement
  8. References

Declaration of personal and funding interests: None.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgement
  8. References
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