Refined Lactulose Hydrogen Breath Test for Small Intestinal Bacterial Overgrowth Subgrouping Irritable Bowel Syndrome With Low and High Breath Hydrogen

Small intestinal bacterial overgrowth (SIBO) is a clinical condition caused by excessive number of bacteria in the small bowel. SIBO is characterized by symptoms of diarrhea, abdominal pain, or bloating which may be associated with excessive gas of small intestine due to increased production by bacterial fermentation in the gut. In the last decade, SIBO has been occupied as a hot topic of interests by a group of researchers because of its potential role in the development of irritable bowel syndrome (IBS).1 In the diagnosis of SIBO, a bacterial count greater than 105 colony-forming units/mL by small bowel culture is believed to be the gold standard.2 But small bowel culture through jejunal aspirate is time-consuming, invasive, and potential for contamination. Due to several flaws of small bowel culture, a number of non-invasive and indirect tests for diagnosing SIBO have been developed. Breath test, the most common indirect method for evaluating SIBO, utilizes the metabolism of carbohydrates by bacterial enzymes, in turn indirectly measures bacterial activity of small bowel. Different carbohydrates have different properties. As lactulose is a non-absorbable carbohydrate, it easily reaches the site of potential overgrowth in the small bowel, although non-absorbed carbohydrate has limitations by the intestinal transit time. In patients with rapid transit, lactulose may produce an early hydrogen peak which makes it difficult to discriminate the true SIBO from a phenomenon by rapid intestinal transit, therefore specificity of lactulose hydrogen breath test (LHBT) is relatively low.3 Pimentel and colleagues4 suggested a concept that SIBO is a major pathogenic mechanism underlying IBS in 2000. They have found 78% of 202 IBS subjects to be positive for LHBT which is suggestive of SIBO. They also demonstrated a significant improvement in symptoms including abdominal pain, bloating, and diarrhea by treating SIBO with antibiotics and converted many IBS patients from Rome criteria positive to negative. Since then, SIBO has been proposed as an etiologic factor in IBS, but also the potential role of SIBO in IBS has been strongly debated about the methods used in diagnosing SIBO. A prevalence of SIBO in subjects meeting diagnostic criteria for IBS varies from 4% to 64%, depending on the kind of test and criteria used to define a positive result.5 In addition, a recent well-designed study from the US6 using LHBT to diagnose SIBO could not discriminate patients with IBS from healthy subjects, which was a consistent finding the authors demonstrated previously.7 Therefore, the proposed etiologic role of SIBO diagnosed by LHBT in IBS patients is controversial and the correlation between the normalization of the LHBT following antibiotic treatment and symptom improvement has become less clear. Glucose, on the other hand, is rapidly absorbed in the proximal small bowel. Thereby detecting hydrogen in this test means SIBO in a proximal location. Glucose hydrogen breath test (GHBT) is the most commonly used test in the diagnosis of SIBO, although GHBT may be less sensitive for the diagnosis of SIBO since it is absorbed in the proximal small bowel. GHBT has been reported to have a overall sensitivity between 25% to 93% and a specificity from 34% to 96% in detecting SIBO.3,5 In this issue of the Journal of Neurogastroenterology and Motility, Ghoshal et al. reported the frequency of SIBO in patients with IBS and chronic non-specific diarrhea (CNSD) with comparison to healthy controls by using GHBT. The authors found that SIBO was more common in patients with CNSD (21.9%) than those with IBS (8.5%) and healthy controls (2%). Since CNSD including diarrhea predominant IBS (D-IBS) had higher frequency of SIBO, the authors suggested clinicians to consider testing for SIBO among them. However, since false positive GHBT could result from rapid intestinal transit in patients with diarrhea, the frequency of SIBO in patients with CNSD and D-IBS demonstrated in the author's study might have been overestimated in part.

Aim: to assess the rate and pattern of the clinical course of small intestinal bacterial overgrowth (SIBO) in irritable bowel syndrome (IBS). Patients and Methods: this study enrolled 100 patients aged 18–68 (mean age 33.5 [26; 46.25] years) with established IBS. The patients were divided into two groups. The IBS with diarrhea (IBS+D) group included 54 patients (mean age 36 [23.0; 49.5] years). The IBS without diarrhea (IBS–D) group included 46 patients (mean 37 [24.5; 49.5] years). All patients underwent lactulose hydrogen breath test using Gastroplus+ monitor to establish SIBO. A positive lactulose hydrogen breath test (a rise of ≥ 20 ppm by 90 min with dual-peak profile or a steady growth of ≥ 12 ppm from baseline in hydrogen) suggested SIBO. Medical history, clinical and lab tests, and the parameters of the quality of life (QoL) using SF-36 and QOL questionnaires were evaluated. Results: the occurrence of SIBO in patients with IBS was 32%, i.e., 37% in the IBS+D group and 28% in the IBS–D group. Multivariate analysis has demonstrated that flatulence in IBS increases the chances of having SIBO by 110.9 times. Univariate analysis revealed universal clinical associations of SIBO with bloating, flatulence, nausea, weakness, tearfulness, and irritability in IBS. Hepatic steatosis is typical for IBS with SIBO (OR=1.75, 95% CI 1.01–3.99, p=0.037). The use of loperamide in IBS+D is associated with a 2.2-fold increase in SIBO risk. SIBO in IBS is associated with a reduction in QoL, as demonstrated by most SF-36 scales (physical and emotional health) and QOL. Conclusions: SIMO in IBS mimics exacerbation, thereby resulting in the prescription of inadequate treatment. KEYWORDS: irritable bowel syndrome, small intestinal bacterial overgrowth, hydrogen respiratory test, quality of life. FOR CITATION: Kulygina Yu.A., Osipenko M.F. Course of irritable bowel syndrome associated with small intestinal bacterial overgrowth. Russian Medical Inquiry. 2022;6(5):232–236 (in Russ.). DOI: 10.32364/2587-6821-2022-6-5-232-236.

Lactulose breath testing, bacterial overgrowth, and IBS: just a lot of hot air?

Objective To compare the tracing effects of radionuclide and barium sulfate on lactulose hydrogen breath test (LHBT), and to explore the value of LHBT combined with radionuclide imaging in the diagnosis of small intestinal bacterial overgrowth (SIBO) in patients with irritable bowel syndrome (IBS). Methods From November 2010 to November 2012, 89 patients (47 males, 42 females; mean age (45.7±12.9) years) with IBS and 13 healthy volunteers (9 males, 4 females; mean age (43.3±8.6) years) were enrolled in this prospective study. All the subjects underwent LHBT combined with radionuclide imaging. Recording the time when the increment of H2 value >0.005‰ and the OCTT of the radionuclide. Four healthy volunteers also underwent LHBT combined with barium sulfate 1 week after radionuclide imaging. The location of barium sulfate was recorded when H2 value increment >0.020‰. Patients with SIBO received rifaximin treatment, and the effect was observed. χ2 test, Pearson correlation analysis and Wilcoxon rank sum test were used to analyze the data. Results (1)In LHBT combined with barium sulfate test, barium sulfate was found still stagnating in small intestine by abdominal X-ray when H2 value increment >0.020‰ in 4 healthy volunteers, and barium sulfate didn′t reach the colon in delayed imaging in 1 patient. (2) The rates of SIBO detected by LHBT in IBS patients and healthy volunteers were significantly different (43.8%(39/89) vs 5/13; χ2=0.133, P=0.716), and those detected by LHBT combined with radionuclide imaging were also significantly different (39.3%(35/89) vs 1/13; χ2=4.970, P=0.026). (3)The time of H2 value increased >0.005‰ correlated well with OCTT in 13 healthy volunteers ((73±31) and (50±19) min; r=0.871, P<0.001) and 54 IBS patients without SIBO ((83±34) and (66±28) min; r=0.735, P<0.001), but there was no correlation in 35 IBS patients with SIBO ((36±30) and (75±30) min ; r=0.304, P=0.076). (4)A total of 34 SIBO-positive patients received a rifaximin treatment, with a significant improvement in the frequency of abdominal pain and abdominal distension after the treatment according to Rome Ⅲ diagnostic criteria: 5(4, 6) vs 4(3, 5), 4(1, 6) vs 0(0, 4)(z values: -4.842 and -5.388, both P<0.001). Conclusion LHBT alone is not a valid test for SIBO, and LHBT combined with radionuclide imaging is a good candidate for SIBO diagnosis. Key words: Blind loop syndrome; Irritable bowel syndrome; Breath tests; Lactulose; Hydrogen; Technetium Tc 99m pentetate

Small intestinal bacterial overgrowth and sugar malabsorption (lactose, fructose, sorbitol) may play a role in irritable bowel syndrome. The lactulose breath test is a reliable and non-invasive test for the diagnosis of small intestinal bacterial overgrowth. The lactose, fructose and sorbitol hydrogen breath tests are widely used to detect specific sugar malabsorption. To assess the extent to which small intestinal bacterial overgrowth may influence the results of hydrogen sugar breath tests in irritable bowel syndrome patients. We enrolled 98 consecutive irritable bowel syndrome patients. All subjects underwent hydrogen lactulose, lactose, fructose and sorbitol hydrogen breath tests. Small intestinal bacterial overgrowth patients were treated with 1-week course of antibiotics. All tests were repeated 1 month after the end of therapy. A positive lactulose breath test was found in 64 of 98 (65%) subjects; these small intestinal bacterial overgrowth patients showed a significantly higher prevalence of positivity to the lactose breath test (P < 0.05), fructose breath test (P < 0.01) and sorbitol breath test (P < 0.01) when compared with the small intestinal bacterial overgrowth-negatives. Small intestinal bacterial overgrowth eradication, as confirmed by negative lactulose breath test, caused a significant reduction in lactose, fructose and sorbitol breath tests positivity (17% vs. 100%, 3% vs. 62%, and 10% vs. 71% respectively: P < 0.0001). In irritable bowel syndrome patients with small intestinal bacterial overgrowth, sugar breath tests may be falsely abnormal. Eradication of small intestinal bacterial overgrowth normalizes sugar breath tests in the majority of patients. Testing for small intestinal bacterial overgrowth should be performed before other sugar breath tests tests to avoid sugar malabsorption misdiagnosis.

To explore the relationship between small intestinal bacterial overgrowth (SIBO) and irritable bowel syndrome (IBS). Fifty IBS patients in the hospital from January 2015 to December 2015 were assigned to the treatment group, and 50 healthy persons were assigned to the control group. Lactulose hydrogen and methane breath test were performed to measure the percentage of SIBO and oro-cecal transit time (OCTT) in treatment group and control group. These subjects were further assigned to negative SIBO group and positive SIBO group to analyze the scores of symptoms. The percentage of positive SIBO in the treatment group (72%, 36/50) was significantly higher (p<0.05) than the control group (38%, 19/50). The scores of symptoms on the episode of IBS were not significantly different between the positive SIBO subgroup and the negative SIBO subgroup. The scores of symptoms in breath test were not significantly different between the positive SIBO subgroup and the negative SIBO subgroup. The OCTT in the treatment group (69.34±1.27 min) was significantly lower (p<0.05) than the control group (85.16±1.75 min). The OCTT in the positive SIBO group (88.57±4.62 min) was significantly higher (p<0.05) than the control group (73.42±5.25 min). The results of lactulose hydrogen and methane breath test in the treatment group were positively correlated (r = 0.987, p<0.01). The results of lactulose hydrogen and methane breath test in the control group after oral administration of lactulose were also positively correlated (r = 0.736, p<0.01). SIBO was related to IBS and could prolong OCTT, yet not worsen IBS.

Although studies indicate that small intestinal bacterial overgrowth (SIBO) is prevalent in irritable bowel syndrome (IBS), it remains unclear whether SIBO causes IBS. This review presents an epidemiologic and evolutionary inquiry that questions the bacterial overgrowth hypothesis of IBS, as follows. (1) Although the hypothesis may be biologically plausible, there is also a strong rationale for competing hypotheses; it is unlikely that SIBO is the predominant cause of IBS in all comers, because competing explanations are sensible and defensible. Moreover, data indicate that the test used to promulgate the SIBO hypothesis - the lactulose hydrogen breath test - may not have measured SIBO in the first place. (2) We do not have evidence of SIBO being absent before IBS symptoms, and present after IBS emerges. (3) There is not a dose-response relationship between small intestinal microbiota and IBS symptoms. (4) The relationship between SIBO and IBS is highly inconsistent among studies. (5) Many effective IBS therapies do not address SIBO at all, yet have a more favorable "number needed to treat" than antibiotics. (6) IBS does not behave like a traditional infectious disease, suggesting that microbes may not principally cause the syndrome. (7) Other factors may confound the relationship between SIBO and IBS, including proton pump inhibitors. (8) Whereas the brain-gut hypothesis is evolutionary sensible, the bacterial hypothesis is harder to defend from an evolutionary perspective. The article concludes that bacteria may contribute to some IBS symptoms, but that bacteria cannot be the only explanation, and a causal link between SIBO and IBS is not secure.

Purpose: Many patients (80–90%) with IBS consider bloating their most bothersome symptom. Recent studies suggest a link between abdominal bloating and/or irritable bowel syndrome (IBS) and small intestinal bacterial overgrowth (SIBO). The prevalence of SIBO in patients with bloating, with or without IBS, is unknown. We determined the prevalence of SIBO in patients referred for lactulose breath test (LBT) and response to treatment for SIBO in patients with bloating. Methods: Selection criteria for enrollment included; >18 years of age and LBT with bloating as a symptom at the UUHSC from Jan 2004 to May 2007. A chart review was performed to collect information including; indication for LBT, LBT results, presence or absence of IBS and treatment and response. SIBO was diagnosed by LBT. An LBT positive result was defined as an early rise (<90 min) in hydrogen (>20 ppm) or methane (>12 ppm). IBS was diagnosed clinically. A positive response was defined as moderate or greater improvement by patient or physician subjective criteria. Chi square or Fisher's exact test were used to make comparisons between groups. Results: A total of 255 breath tests were performed. There were 169 patients with bloating as a symptom (9 with no result). The mean age for patients with bloating was 47.6 years ± 15.8, 69% were female. The prevalence of positive SIBO in patients with bloating was 51% (82/160). The prevalence of positive SIBO was different between patients referred for bloating vs. referred for other reasons ((82/160 (51%) vs. 27/86 (31%), P= 0.004)). The prevalence of positive SIBO in patients with bloating and IBS was 22/42 (52%). There was no difference in the prevalence of SIBO in patients with and without IBS ((22/42 (52%) versus 62/118 (46%) P= NS)). 82% (28/34) of patients with bloating and positive LBT responded to antibiotic treatment vs. 33% (3/9) of patients with bloating and negative LBT (P= 0.008, OR = 9.3). Patients were followed for 10.4 ± 7.7 months for response. Conclusion: In patients with bloating referred for LBT, SIBO positivity was significantly higher than in patients referred for other reasons. In patients with bloating, SIBO positivity was not different in patients with and without IBS. Patients with bloating and positive SIBO by LBT are significantly more likely to respond to antibiotic Rx than patients with bloating and negative SIBO by LBT. Further investigation of factors associated with bloating, SIBO and response to antibiotic therapy is warranted.

Objective To investigate the incidence of small intestinal bacterial overgrowth (SIBO) and systemic low-grade inflammation in patients with irritable bowel syndrome (IBS). Methods From June to October in 2017, 50 cases of IBS patients who met Rome Ⅳ criteria were consecutively collected at Outpatient Department of Gastroenterology of Shanghai Huashan Hospital. The incidence of SIBO was detected by hydrogen lactulose breath test (LBT) and methane LBT. The incidence of systemic low-grade inflammation in IBS patients was determined by fractional exhaled nitric oxide(FeNO) breath test. Chi-square test was used for statistical analysis. Results Among 50 IBS patients, the positive rate of FeNO was 70%(35/50), and the number of FeNO positive cases in diarrhea-predominant (n=28), constipation-predominant (n=14) and mix-type (n=8) IBS paitents was 18, 11 and six, respectively, and the difference was not statistically significant among three groups (χ2=1.020, P=0.600). The incidence rate of SIBO was 60% (30/50), with 20 cases (40%) being only positive for hydrogen LBT, seven cases (14%) being methane LBT, and three cases (6%) being both positive. The numbers of hydrogen LBT and methane LBT in diarrhea-predominant, constipation-predominant, and mix-type IBS patents were 17, three, three and two, six, two, respectively. There were statistically significant differences in positive rates of hydrogen LBT and methane LBT among three groups (χ2=6.076 and 6.392, both P<0.05). The positive rate of FeNO in IBS patients with SIBO was higher than that of IBS patients without SIBO (90%, 27/30 vs. 40%, 8/20), and the difference was statistically significant (χ2=14.286, P<0.01). Conclusions Combination of hydrogen LBT and methane LBT has a higher detection rate of SIBO than traditional single hydrogen LBT. There is a correlation between SIBO and systemic low-grade inflammation in IBS patients. Key words: Irritable bowel syndrome; Small intestinal bacterial overgrowth; Lactulose breath test; Systemic low-grade inflammation

Inflammatory bowel disease (IBD) consists of Ulcerative colitis (UC) and Crohn's disease (CD). These two conditions share many common features-diarrhea, bloody stools, weight loss, abdominal pain, fever and fatigue. Small intestinal bacterial overgrowth (SIBO) is frequent in patients with CD but it has not been studied in UC Indian patients. The study was planned to measure orocecal transit time (OCTT) and SIBO in UC and CD patients. One hundred thirty-seven patients of IBD (95 UC and 42 CD) and 115 healthy controls were enrolled. OCTT and SIBO were measured by lactulose and glucose hydrogen breath test respectively. Concentration of hydrogen and methane were measured by SC microlyser from Quintron, USA. Mean±standard deviation (SD) of OCTT in patients of IBD was significantly higher as compared to controls. Furthermore, OCTT was significantly higher in CD patients as compared to UC patients. It was also observed that occurrence of SIBO was significantly higher in IBD patients as compared to controls. The occurrence of SIBO in CD (45.2%) was significantly higher as compared to patients in UC (17.8%) group. Percentage of methane positive IBD patients (2.9%) was significantly lower as compared to methane positive controls (24.4%). OCTT was significantly delayed in IBD patients as compared to controls and in CD patients as compared to UC patients. OCTT was significantly higher in SIBO positive IBD patients as compared to SIBO negative patients. Thus, we can suggest that delayed OCTT would have been the cause of increased SIBO in these patients.

Introduction and study aim: IBS is the most common functional disorder of gastrointestinal (GI) tract. It is shown that intestinal microbiota plays an important role in the pathogenesis of Irritable Bowel Syndrome (IBS). Recent studies have been shown that probiotics could be effective in the improvement of IBS symptoms by changing gut normal microflora. In this study we investigated the probiotics’ efficacy in prevention of small intestinal bacterial overgrowth (SIBO) recurrence among patients with IBS. Patients and Methods: In a double blind clinical trial, patients with IBS and SIBO who were diagnosed based on positive Hydrogen breath test, initially received antibiotics for a period of 10 days and then randomly divided into 2 groups (Mutaflor probiotic and placebo) after confirmation of negative Hydrogen breath test. After 3 months treatment, breath tests were repeated and frequency of SIBO recurrence was compared between 2 groups. Results: Among 172 patients with IBS and SIBO, 159 cases included the study and after antibiotic treatment and negative breath tests, eventually 156 patients were analyzed. Both groups had similar demographic characters such as age, sex, IBS type and PPI consumption. Frequency of SIBO recurrence were significantly lower in the probiotic group than the placebo group (P=0.033). Frequency rate of constipation and mixed type of IBS were almost similar in both groups (P>0.05) and only there was a significant difference in SIBO frequency between 2 groups as diarrhea dominant IBS (P<0.05). Conclusion: Our study showed that Mutaflor probiotic has beneficial effects on reduction of SIBO recurrence among IBS patients and could be successfully used for treatment of these patients.

Small intestinal bacterial overgrowth (SIBO) has been implicated in the pathogenesis of irritable bowel syndrome (IBS). Psychosocial factors and low-grade colonic mucosal immune activation have been suggested to play important roles in the pathophysiology of IBS. In total, 94 patients with IBS and 13 healthy volunteers underwent a 10 g lactulose hydrogen breath test (HBT) with concurrent 99mTc scintigraphy. All participants also completed a face-to-face questionnaire survey, including the Hospital Anxiety and Depression Scale, Life Event Stress (LES), and general information. Serum tumour necrosis factor-α, interleukin- (IL-) 6, IL-8, and IL-10 levels were measured. The 89 enrolled patients with IBS and 13 healthy controls had no differences in baseline characteristics. The prevalence of SIBO in patients with IBS was higher than that in healthy controls (39% versus 8%, resp.; p = 0.026). Patients with IBS had higher anxiety, depression, and LES scores, but anxiety, depression, and LES scores were similar between the SIBO-positive and SIBO-negative groups. Psychological disorders were not associated with SIBO in patients with IBS. The serum IL-10 level was significantly lower in SIBO-positive than SIBO-negative patients with IBS.

Su2034 Diagnosis of Small Intestinal Bacterial Overgrowth by Lactulose Hydrogen Breath Test With Scintigraphic Oro-Caecal Transit Test: Methodological Validation of Diagnostic Criteria in Healthy Controls and Patients With Diarrhea Predominant Irritable Bowel Syndrome

Introduction Although controversial, small intestinal bacterial overgrowth (SIBO) has been associated with irritable bowel syndrome (IBS) (1). However, little is known regarding the effect of concomitant SIBO in patients with IBS in terms of symptom burden, quality of life or its effect on gastrointestinal (GI) motility. We aimed to compare the effect of SIBO on symptom burden, quality of life and segmental/panenteric motility in IBS. Methods 27 patients with Rome III defined IBS-mixed bowel habit (IBS-M) (3 male, mean age 36.5 years, range 18–65) underwent a wireless motility capsule (WMC) using a standardised protocol. The WMC concurrently measures pH, pressure and temperature as it traverses the GI tract. Segmental transit was derived from measures around known anatomical landmarks as identified by compartmental pH changes. Ileal and colonic motility measures are presented as area under the curve (AUC) derived from contraction amplitude and frequency. Validated questionnaires assessing GI (verbal descriptor anchored visual analogue scale (VDVAS) assessing sensory intensity (VDVAS-I) and unpleasantness (VDVAS-U)), somatic symptoms (Personal Health Questionnaire (PHQ) and quality of life (EQ-5 D) were administered. A standardised lactulose hydrogen breath test was subsequently performed and interpreted according to recently published guidelines (2). Results 14/27 patients (51.8%) were positive for SIBO based on breath testing. Changes in GI motility between SIBO positive and negative patients are shown in Table 1. Patients with concomitant SIBO had higher VDVAS-I and VDVAS-U (147±21 vs. 127±20, p≥0.048 and 135±9.2 vs. 109±6.2, p≥0.02) and somatic symptoms (9.8±3.2 vs. 7.3±2.3, p≥0.03). SIBO positive patients had reduced quality of life in comparison to those without (43.2±16 vs. 60±15, p≥0.008). Conclusions Concomitant SIBO in patients with IBS-M confers a higher gastrointestinal and extra-gastrointestinal symptom burden. Moreover, it is associated with a reduction in quality of life. However, it was not associated with any demonstrable alterations in GI physiology. It is plausible to suggest that such IBS patients with co-existent SIBO may potentially preferentially respond to antimicrobial interventions such as rifaximin. References Aziz et al. Curr Opin Gastro 2017. Rezaie et al. Am J Gastro 2017.

We conducted a systematic review and meta-analysis to compare the prevalence of small intestinal bacterial overgrowth (SIBO) in patients with irritable bowel syndrome (IBS) and controls. Electronic databases were searched up to December 2018 for studies reporting SIBO prevalence in patients with IBS. Prevalence rates, odds ratios (ORs), and 95% confidence intervals (CIs) of SIBO in patients with IBS and controls were calculated. We included 25 studies with 3,192 patients with IBS and 3,320 controls. SIBO prevalence in patients with IBS was significantly increased compared with controls (OR = 3.7, 95% CI 2.3-6.0). In studies using only healthy controls, the OR for SIBO in patients with IBS was 4.9 (95% CI 2.8-8.6). With breath testing, SIBO prevalence in patients with IBS was 35.5% (95% CI 33.6-37.4) vs 29.7% (95% CI 27.6-31.8) in controls. Culture-based studies yielded a SIBO prevalence of 13.9% (95% CI 11.5-16.4) in patients with IBS and 5.0% (95% CI 3.9-6.2) in controls with a cutoff value of 10 colony-forming units per milliliter vs 33.5% (95% CI 30.1-36.9) in patients with IBS and 8.2% (95% CI 6.8-9.6) in controls with a cutoff value of 10 colony-forming unit per milliliter, respectively. SIBO prevalence diagnosed by lactulose breath test is much greater in both patients with IBS (3.6-fold) and controls (7.6-fold) compared with glucose breath test. Similar difference is seen when lactulose breath test is compared with culture methods. OR for SIBO in patients with IBS-diarrhea compared with IBS-constipation was 1.86 (95% CI 1.83-2.8). Methane-positive breath tests were significantly more prevalent in IBS-constipation compared with IBS-diarrhea (OR = 2.3, 95% CI 1.2-4.2). In patients with IBS, proton pump inhibitor was not associated with SIBO (OR = 0.8, 95% CI 0.5-1.5, P = 0.55). This systematic review and meta-analysis suggests a link between IBS and SIBO. However, the overall quality of the evidence is low. This is mainly due to substantial "clinical heterogeneity" due to lack of uniform selection criteria for cases and controls and limited sensitivity and specificity of the available diagnostic tests.