Test For Small Intestinal Bacterial Overgrowth Research Articles

Critical appraisal of the SIBO hypothesis and breath testing: A clinical practice update endorsed by the European society of neurogastroenterology and motility (ESNM) and the American neurogastroenterology and motility society (ANMS).

There is compelling evidence that microbe-host interactions in the intestinal tract underlie many human disorders, including disorders of gut-brain interactions (previously termed functional bowel disorders), such as irritable bowel syndrome (IBS). Small intestinal bacterial overgrowth (SIBO) has been recognized for over a century in patients with predisposing conditions causing intestinal stasis, such as surgical alteration of the small bowel or chronic diseases, including scleroderma and is associated with diarrhea and signs of malabsorption. Over 20 years ago, it was hypothesized that increased numbers of small intestine bacteria might also account for symptoms in the absence of malabsorption in IBS and related disorders. This SIBO-IBS hypothesis stimulated significant research and helped focus the profession's attention on the importance of microbe-host interactions as a potential pathophysiological mechanism in IBS. However, after two decades, this hypothesis remains unproven. Moreover, it has led to serious unintended consequences, namely the widespread use of unreliable and unvalidated breath tests as a diagnostic test for SIBO and a resultant injudicious use of antibiotics. In this review, we examine why the SIBO hypothesis remains unproven and, given the unintended consequences, discuss why it is time to reject this hypothesis and its reliance on breath testing. We also examine recent IBS studies of bacterial communities in the GI tract, their composition and functions, and their interactions with the host. While these studies provide important insights to guide future research, they highlight the need for further mechanistic studies of microbe-host interactions in IBS patients before we can understand their possible role in diagnosis and treatment of patient with IBS and related disorders.

Small Intestinal Bacterial Overgrowth Is Associated with Poor Prognosis in Cirrhosis.

Small intestinal bacterial overgrowth (SIBO) is associated with numerous manifestations of cirrhosis. To determine whether the presence of SIBO affects the prognosis in cirrhosis was the aim of the study. This prospective cohort study included 50 patients. All participants underwent a lactulose hydrogen breath test for SIBO. The follow-up period was 4 years. SIBO was detected in 26 (52.0%) patients: in 10 (52.6%) patients with compensated cirrhosis and in 16 (51.6%) ones with decompensated cirrhosis. Twelve (46.2%) patients with SIBO and four (16.7%) patients without SIBO died within 4 years (p = 0.009). Among patients with decompensated cirrhosis, 8 (50.0%) patients with SIBO and 3 (20.0%) patients without SIBO died (p = 0.027). Among patients with compensated cirrhosis, four (40.0%) patients with SIBO and one (11.1%) patient without SIBO died (p = 0.045). Among patients with SIBO, there was no difference in mortality between patients with compensated and decompensated cirrhosis (p = 0.209). It was the same for patients without SIBO (p = 0.215). SIBO affects the prognosis only in the first year of follow-up in decompensated cirrhosis, and only in subsequent years in compensated cirrhosis. Presence of SIBO (p = 0.028; HR = 4.2(1.2-14.9)) and serum albumin level (p = 0.027) were significant independent risk factors for death in cirrhosis. SIBO is associated with poor prognosis in cirrhosis.

The Impact of Confounders on Symptom-Endoscopic Discordances in Crohn's Disease.

Discordances between clinical and endoscopic Crohn's disease (CD) activity indices negatively impact the utility of clinic visits and efficacy assessments in clinical trials. Bile acid diarrhea (BAD) and small intestinal bacterial overgrowth (SIBO) mimic CD symptoms. This study quantified the impact of BAD and SIBO on the relationship between clinical and endoscopic disease activity indices. CD patients with 7α-hydroxy-4-cholesten-3-one (7C4) serum measurements and/or SIBO breath tests and matched clinical and endoscopic scores were included. Clinical remission (stool frequency [SF] ≤ 1 and abdominal pain score ≤ 1) rates were compared between those with and without (1) endoscopic remission, (2) BAD (7C4 > 55 ng/mL), and (3) SIBO. Of 295 CD patients, 219 had SIBO testing and 87 had 7C4 testing. Patients with elevated 7C4 had lower proportions with clinical remission (14% vs 40%, P = .007) and SF ≤ 1 (14% vs 42%, P = .004) compared to those with normal 7C4. In patients with normal 7C4, higher rates of clinical remission (65% vs 27%, P = .01) and SF ≤ 1 (71% vs 27%, P = .003) existed in patients with endoscopic remission compared to those without endoscopic remission. Conversely, among the entire 295 patient cohorts, nearly identical clinical remission rates existed between those with and without endoscopic remission (25% vs 24%, P = .8), and the Crohn's Disease Patient-Reported Outcome-2 score was not accurate for predicting endoscopic remission (Area Under the Curve (AUC): 0.48; 95% CI, 0.42-0.55). SIBO status did not impact clinical remission rates (P = 1.0). BAD, but not SIBO, contributed to symptom scores. A relationship between endoscopic inflammation and clinical remission rates only existed in patients without 7C4 elevations.

Impact of Small Intestinal Bacterial Overgrowth in Patients with Inflammatory Bowel Disease and Other Gastrointestinal Disorders-A Retrospective Analysis in a Tertiary Single Center and Review of the Literature.

Small intestinal bacterial overgrowth (SIBO) is often found in patients with gut dysbiosis such as irritable bowel syndrome. Recently, the association of SIBO and inflammatory bowel disease (IBD) has been described in some cases. While clinical symptoms might be similar in IBD and SIBO, treatment is quite different for both diseases. Therefore, the differentiation between SIBO or a flare in IBD patients is key to optimizing treatment for these patients. We retrospectively investigated our patients with IBD receiving a glucose breath test for SIBO and correlated the results with the clinical symptoms (clinical remission or active disease). 128 patients with the diagnosis "colitis" were analyzed in our cohort. Fifty-three (41.4%) patients had Crohn's disease and 22 (17.2%) patients were suffering from ulcerative colitis. Seventy-four (57.8%) were female and 54 (42.2%) were male patients. A total of 18 (14.1%) patients had a positive testing for SIBO. Eleven (61.1%) cases were associated with CD patients and two (11.1%) with UC. IBD patients in clinical remission had a positive SIBO in six (19.4%) cases, while IBD patients with active disease were positive in nine (15.3%) cases. The proportion of positive SIBO in active IBD patients was higher; however, it did not reach significance. Older age was a risk factor for SIBO in patients with CD (p < 0.003). In our study, we could show that an increased amount of SIBO was found in IBD patients and was especially more frequent in patients with CD than in those with UC. In UC patients, SIBO rates were not different to patients with other gastrointestinal diseases investigated (e.g., infectious colitis, collagenous colitis, or irritable bowel syndrome). In active IBD, positive SIBO was detected more often numerically compared to quiescent disease; however, due to the low number of patients included, it was not significant. However, older age was a significant risk factor for SIBO in patients with CD. SIBO is of clinical relevance in the vulnerable patient cohort with IBD, and its real prevalence and impact needs to be investigated in further and larger clinical trials.

Plasma levels of intestinal fatty-acid binding protein (I-FABP), abdominal distension and hydrogen concentration after lactitol small intestinal bacterial overgrowth (SIBO) test.

Breath tests with glucose, lactulose or lactitol are useful for diagnosis of small intestinal bacterial overgrowth (SIBO). Nevertheless, they have suboptimal sensitivity and specificity and, indeed, are positive in a considerable number of patients with irritable bowel syndrome (IBS). The complexity in the management of patients with functional intestinal disorders and the availability of these tests are leading to frequent diagnoses of SIBO. Intestinal Fatty-Acid Binding protein (I-FABP) is a protein present in the cytosol of intestinal epithelial cells. Its plasmatic levels have been related to different enteropathies and, therefore, could be a marker of early intestinal damage with unconfirmed clinical utility. Hence, we have studied the plasmatic I-FABP level of patients who are requested a lactitol test to confirm SIBO and related it to clinical and laboratory characteristics and SIBO test results.

Diagnosis of Small Intestinal Bacterial Overgrowth

Small intestinal bacterial overgrowth (SIBO) occurs when the small bowel is colonized by high numbers of abnormal microorganisms. There is no gold standard diagnostic test for SIBO. Both small bowel aspiration and breath testing have limitations as diagnostic tests. However, breath testing has the practical advantages of being readily available, inexpensive, and noninvasive.

Current and Future Approaches for Diagnosing Small Intestinal Dysbiosis in Patients With Symptoms of Functional Dyspepsia.

The development and application of next generation sequencing technologies for clinical gastroenterology research has provided evidence that microbial dysbiosis is of relevance for the pathogenesis of gastrointestinal and extra-intestinal diseases. Microbial dysbiosis is characterized as alterations of diversity, function, and density of the intestinal microbes. Emerging evidence suggests that alterations of the gastrointestinal microbiome are important for the pathophysiology of a variety of functional gastrointestinal conditions, e.g., irritable bowel syndrome (IBS) and functional dyspepsia (FD), also known as disorders of brain-gut axis interaction. Clinicians have for many years recognized that small intestinal bacterial overgrowth (SIBO) is typified by a microbial dysbiosis that is underpinned by abnormal bacterial loads in these sites. SIBO presents with symptoms which overlap with symptoms of FD and IBS, point toward the possibility that SIBO is either the cause or the consequence of functional gastrointestinal disorders (FGIDs). More recently, new terms including “intestinal methanogen overgrowth” and “small intestinal fungal overgrowth” have been introduced to emphasize the contribution of methane production by archea and fungi in small intestinal dysbiosis. There is emerging data that targeted antimicrobial treatment of SIBO in patients with FD who simultaneously may or may not have IBS, results in symptom improvement and normalization of positive breath tests. However, the association between SIBO and FGIDs remains controversial, since widely accepted diagnostic tests for SIBO are lacking. Culture of jejunal fluid aspirate has been proposed as the “traditional gold standard” for establishing the diagnosis of SIBO. Utilizing jejunal fluid culture, the results can potentially be affected by cross contamination from oropharyngeal and luminal microbes, and there is controversy regarding the best cut off values for SIBO diagnosis. Thus, it is rarely used in routine clinical settings. These limitations have led to the development of breath tests, which when compared with the “traditional gold standard,” have sub-optimal sensitivity and specificity for SIBO diagnosis. With newer diagnostic approaches–based upon applications of the molecular techniques there is an opportunity to characterize the duodenal and colonic mucosa associated microbiome and associated gut microbiota dysbiosis in patients with various gastrointestinal and extraintestinal diseases. Furthermore, the role of confounders like psychological co-morbidities, medications, dietary practices, and environmental factors on the gastrointestinal microbiome in health and disease also needs to be explored.

Performance and Interpretation of Hydrogen and Methane Breath Testing Impact of North American Consensus Guidelines

BackgroundHydrogen and methane breath tests (HMBT) are widely used clinical investigations but lack standardization. To address this, the North American Consensus (NAC) group published evidence-based recommendations for HMBT.AimsTo evaluate results obtained using NAC recommendations for HMBT, compared to retrospective data that utilized guidelines previously recommended.MethodsHMBT data from 725 patients referred for small intestinal bacterial overgrowth (SIBO) and/or carbohydrate malabsorption (CM) testing were analyzed. Data were compared regarding dose of substrate for SIBO testing (16 vs. 10 g lactulose, and 50 vs. 75 g glucose) and the effect of post-ingestion sampling period for malabsorption testing. The effect of different recommended cut-off values for SIBO were examined.ResultsSubstrate dose did not affect methane production. 10 g lactulose significantly reduced positive SIBO results compared to 16 g lactulose (42 vs. 53%, p = 0.04). 75 g glucose significantly increased positive results compared to 50 g glucose (36 vs. 22%, p = 0.04). Provoked symptoms were significantly more prevalent in patients testing positive by both North American Consensus and Ledochowski cut-off values.34.5% of patients tested positive for CM at 180-min compared to 28% at 120-min (not significant, p = 0.19).Conclusions and Inferences10 g lactulose substrate produces fewer positive SIBO results than 16 g lactulose, while 75 g glucose dose produces more positive SIBO results than 50 g. Performing CM breath tests for 180 min increases number of positive results when compared to 120 min. SIBO cut-off timings require further investigation, but our findings broadly support the NAC recommendations for SIBO and CM testing.

S1359 Determinants and Outcomes of Pre-Test Elevation in Hydrogen/Methane Breath Testing for SIBO

Introduction: Small intestinal bacterial overgrowth (SIBO) is characterized by excess colonic microbe colonization in the small bowel. This can result in malabsorption, and patients typically present with a wide array of gastrointestinal symptoms, making it difficult to diagnose through clinical presentation alone. Diagnosis is established by elevated hydrogen or methane levels on breath test. It has been hypothesized that hydrogen dominant SIBO is associated with diarrhea while methane dominant is associated with constipation. We aimed to assess whether lifestyle factors, certain risk factors or common symptoms are characteristic of SIBO positivity. Methods: Patients undergoing SIBO breath testing (n=308) were surveyed. The survey included questions about stool frequency, stool consistency, PPI usage, antibiotic usage, dietary factors, and symptoms. Results from the survey and breath test were compared. Results: When comparing PPI usage, antibiotic usage, experienced symptoms, kefir/yogurt/probiotic ingestion, stool consistency, or stool frequency no significant difference was found between patients who tested positive versus negative for SIBO (Table 1). However, patients who did not have a daily stool had double the odds of having a positive breath test (OR = 0.50, CI: [0.28-0.88]). Additionally, the mean age for patients tested positive for SIBO (59.62) was significantly higher than patients tested negative for SIBO (52.14)(P = < 0.001). Conclusion: SIBO is a difficult to characterize disease with a variety of symptoms. When assessing patients’ dietary factors (kefir, yogurt, or probiotic ingestion), risk factors (PPI and antibiotic usage), and experienced symptoms, no unifying variable predictive of SIBO positivity was determined. Interestingly, patients who did not at least have a daily stool had double the odds of having a positive breath test, possibly suggesting the predominance of constipation-like symptoms in SIBO positive patients in this population. Additionally, the mean age for patients positive for SIBO was significantly higher than patients tested negative for SIBO. Further research is necessary to characterize lifestyle and clinical factors influencing SIBO positivity and to understand the intricacies between breath testing and patient symptoms.Figure 1.: Figure 1a and 1b: Proportions with Positive vs Negative SIBO Breath TestTable 1.: Demographics and Variables Affecting SIBO Positivity.

S1370 Small Intestinal Bacterial Overgrowth Prevalence in Patients With Systemic Sclerosis

Introduction: Currently, there is a paucity of information regarding the prevalence of small intestinal bacterial overgrowth (SIBO) in patients with systemic sclerosis (SSc). SIBO occurs when the small bowel becomes colonized with the bacteria normally found in the colon and can cause a variety of gastrointestinal (GI) symptoms including bloating, nausea, abdominal pain, flatulence, and diarrhea. Several risk factors for developing SIBO have been identified including intestinal dysmotility, anatomic disorders, and gastric hypochlorhydria, among others. We hypothesized that patients with SSc would have a higher incidence of SIBO than patients who have similar symptoms without underlying SSc. Methods: We performed a retrospective review of patients with and without SSc who underwent testing for SIBO between 2007-2017 (n = 2545). SIBO was diagnosed either via carbohydrate breath testing or small bowel aspiration during esophagogastroduodenoscopy (EGD). Breath testing was considered positive for SIBO if the concentration of exhaled hydrogen demonstrated a rise to at least 20 parts per million. Small bowel aspirates obtained during EGD were sent for quantitative cultures. A positive culture was defined as bacterial growth of >105 cfu/mL. Comparison was made between patients with SSc who tested positive for SIBO and patients without SSc who tested positive for SIBO. Other variables were also collected including demographic data, narcotic use, proton pump inhibitor use, and diagnosis of gastroparesis Results: A total of 2545 patients were reviewed (Table 1). Forty-eight of 126 patients with SSc tested positive for SIBO and 342 of 2419 patients without SSc tested positive for SIBO (38.1% vs 14.1%, P = 0.0001). Patients with SSc also had a higher incidence of gastroparesis, proton-pump inhibitor use, and abdominal surgeries compared with patients without SSc (Table 1). Conclusion: This is one of the largest studies so far investigating SIBO in patients with SSc. We found that patients with SSc had a higher incidence of SIBO compared with patients who had similar GI symptoms without underlying SSc. This is likely related to the fact that patients with SSc often have multiple risk factors for SIBO compared with their non-SSc counterparts. Because a large majority of patients with SSc also have GI symptoms, clinicians should consider the diagnosis of SIBO and initiate testing early.Table 1.: Patients with SIBO with and without systemic sclerosis

Irritable bowel syndrome, urolithiasis and role of microbiota in their comorbidity

Urolithiasis (UL) is a polyetiological disease that depends on climate, age, diet, infections, and the presence of concomitant diseases. The major risk factors for UL include inflammatory and functional bowel disease. The aim was analysis of changes in the bowel microbiota in patients with UL combined with Irritable Bowel Syndrome (IBS), as well as the effect of microbiome correction on the recurrence rates of oxalate UL in these patients. Material and Methods: We selected 320 patients with UL with oxalate stones and concomitant IBS. Small Intestinal Bacterial Overgrowth (SIBO) was assessed in all patients and microbiome analisis was performed. Patients has 3 year observation period. A breath test for SIBO was performed every 6 months. The determination of various taxa of fecal microbiota was carried out. Patients with UL+IBS were randomly divided into 2 groups. Group I involved 120 patients who were prescribed with rifaximin. Group II-control, involved 200 patients. Results: Initially, in patients with UL+IBS, the incidence of SIBO detection was 65%. The study of microbiome phylotypes has found the significant decrease in Firmicutes as well as Akkermansia muciniphila in patients with IBS-related oxalate UL. After 6 months SIBO in patients of Group I was positive in 54 (46.6%) patients, but following 3 years 15 (12.9%) patients. In Group II, following 6 months there were 123 (63.7%) patients with SIBO, following 3 years 149 (77.2%) patients. And after 3 years we found a significant decrease in the relative risk of recurrence of UL to 0.608 in Group I. Conclusions: Patients with UL have symptoms of IBS in 19.5% of cases. SIBO was diagnosed by 5.2 times more often in UL combined with IBS. Repeated courses of rifaximin, every 6 months, in patients with SIBO and persistent symptoms of IBS were accompanied by a significant decrease in recurrences of UL

S1300 The Relationship Between Serum IgA Level, Small Intestinal Bacterial Overgrowth (SIBO), and Ethnicity

INTRODUCTION: Secretory immunoglobulin A (IgA) is critical in preventing pathogen overgrowth in the gastrointestinal tract. IgA production is stimulated by the colonization of bacteria. The relationship between serum IgA level & incidence of small intestinal bacterial overgrowth (SIBO) in symptomatic patients has not been studied. Patients with selective IgA deficiency with a critically low serum IgA level (< 7 mg/dL) & normal IgM & IgG levels have a 10- to 20-fold increased risk for celiac disease, however an increased risk for SIBO has not been documented. The aim of this retrospective observational study was to determine the relationship of abnormal serum IgA level as a possible risk factor for SIBO with stratification based on ethnicity. METHODS: A retrospective electronic chart review was performed of all patients seen in the gastroenterology clinic who underwent breath hydrogen testing for SIBO & had serum IgA level measurement from 12/1/2010 to 1/1/2020 via clinical data query. The relationship between serum IgA level, SIBO percentage in symptomatic patients via breath test results & patient demographics was studied. Continuous variables are presented by median & IQR. Categorical variables are presented by counts & percent. X2 test was used to test association between breath test results (abnormal/negative) & IgA levels (3 levels- reduced, normal & elevated). All statistical tests were performed at an α = 0.05 level of significance, using two-sided tests. RESULTS: 561 patients underwent breath hydrogen testing from 12/1/2010 to 1/1/2020 with documented serum IgA level, of which 73% were female, 53.7% Hispanic. 39.4% of breath tests were positive for SIBO; 3.7% were nondiagnostic. SIBO percentage was highest in patients with reduced IgA level (14/29, 48.3%) compared to normal (40.5%) or elevated IgA level (41.4%) (P = 0.7067). Reduced IgA level was more common in non-Hispanics than Hispanics (7.66 vs. 3.44%) whereas elevated IgA level was more common in Hispanics (7.22 vs. 3.40%). SIBO was more common in non-Hispanics with reduced IgA level than Hispanics (11/19, 57.9% vs. 3/12, 25%). CONCLUSION: The overall rate of SIBO is higher though not statistically significant in patients with reduced IgA. This may be due to an overall paucity of patients with abnormal IgA level in our population. Further, differences in ethnicity may impact IgA level & potential for SIBO. Future larger studies should explore the relationship of abnormal IgA level, SIBO & ethnicity.

The role of small intestinal bacterial overgrowth and false positive diagnosis of lactose intolerance in southwest Hungary-A retrospective observational study.

BackgroundLactose intolerance is a frequent gastrointestinal disease affecting 47% of the Eastern European population. Small intestinal bacterial overgrowth (SIBO) leads to carbohydrate malabsorption and therefore to false results during lactose breath and tolerance tests.ObjectivesWe aimed to assess the prevalence of lactose maldigestion and intolerance in Hungary and to investigate the role of combined diagnostic method and testing for SIBO in reducing false results.MethodsWe retrospectively analyzed data from 264 adult symptomatic patients who underwent 50g lactose breath and tolerance tests in parallel over a one-year period at our center. A ≥20 ppm elevation of H2 or less than 1.1 mmol/l rise of blood glucose was diagnostic for lactose maldigestion. Patients with maldigestion who had symptoms during the test were defined as lactose intolerant. Patients with an early (≤90 min) significant (≥20 ppm) rise of H2 during lactose and/or lactulose breath tests were determined to have SIBO. Patients with slow/rapid oro-cecal transit and inappropriate preparation before the test were excluded.Results49.6% of the 264 patients had lactose maldigestion, and 29.5% had lactose intolerance. The most frequent symptom was bloating (22.7%), while 34.8% of the study population and 60% of the symptomatic patients had SIBO. In 9.1% and 9.8% of the patients, the lactose breath and tolerance test alone gave false positive result compared with the combined method. SIBO was present in 75% of the false positives diagnosed with breath test only.ConclusionsThe prevalence of lactose intolerance is lower in Hungary compared to the Eastern European value (29.5% vs 47%), so it is worth performing a population-based prospective analysis in this area. A combination of lactose breath and tolerance tests and the careful monitoring of results (with early H2 rise, lactulose breath test, etc.) can decrease the false cases caused by e.g. SIBO.

A meta-analysis on small intestinal bacterial overgrowth in patients with different subtypes of irritable bowel syndrome.

Enteric microbiota is increasingly being recognized as an important factor in the pathogenesis of irritable bowel syndrome (IBS). The reported prevalence of small intestinal bacterial overgrowth (SIBO) in subjects with IBS is highly variable, and there is no consensus on the role of SIBO in different subtypes of IBS, and indications and methods of testing. A comprehensive literature search was performed for studies applying tests for SIBO in subjects with IBS. After applying prospectively decided exclusion criteria, the eligible papers were examined using a meta-analysis approach for the prevalence of SIBO in subjects with IBS using different tests. The odds ratios of SIBO among subjects with IBS as compared with healthy controls using different tests were calculated. Of the available studies (22, 17, 5, and 3 using lactulose and glucose hydrogen breath tests [LHBT and GHBT], jejunal aspirate culture, and more than one tests, respectively) meeting the inclusion criteria, 36.7% (95% confidence interval [CI] 24.2-44.6) had a positive test for SIBO. Patients with IBS were 2.6 (95% CI 1.3-6.9) and 8.3 (95% CI 3.0-5.9) times more likely to have a positive test for SIBO as compared with healthy controls using GHBT and jejunal aspirate culture, respectively. Patients with diarrhea-predominant IBS were more likely to have positive GHBT as compared with the other subtypes. Patients with IBS were more likely to have SIBO as compared with healthy subjects using GHBT and jejunal aspirate culture but not using LHBT. Patients with diarrhea-predominant IBS more often have SIBO.

Is small intestinal bacterial overgrowth a cause of hyperdynamic circulation in cirrhosis?

Small intestinal bacterial overgrowth (SIBO) and hemodynamic changes are common in cirrhosis. We wanted to examine our hypothesis whether SIBO leads to hemodynamic changes in cirrhosis. A total of 50 patients with cirrhosis and 15 healthy controls were enrolled in a pilot prospective study. All participants underwent the lactulose hydrogen breath test for SIBO and echocardiography with a simultaneous assessment of blood pressure and heart rate. Cardiac output and systemic vascular resistance were calculated. Study participants with SIBO had a lower systolic blood pressure and systemic vascular resistance compared to those without SIBO and to healthy controls (110.2±12.3 mmHg vs. 126.2±21.0 mmHg and 121.2±9.8 mmHg; p=0.005 and p=0.011, respectively; 1312±352 dyn•s•cm-5 vs. 1704±424 dyn•s•cm-5 and 1648±272 dyn•s•cm-5; p=0.001 and p=0.006, respectively), but a higher cardiac output (5.38±1.41 l/min vs. 4.52±1.03 l/min and 4.40±0.68 l/min; p=0.034 and p=0.041, respectively) and C-reactive protein (10.5[1.2-16.5] mg/l vs. 2.8[0.6-9.1] mg/l; p=0.028; no comparison with healthy controls). There were no significant differences between patients without SIBO and healthy controls with regard to systolic blood pressure (p=0.554), systemic vascular resistance (p=0.874), and cardiac output (p=0.795). SIBO was associated with vasodilation and hyperdynamic circulation in decompensated cirrhosis (p=0.002; p=0.012), but not in compensated cirrhosis (p=1.000; p=0.474). SIBO is associated with hyperdynamic circulation and other hemodynamic changes in cirrhosis and may be a principal factor causing these through systemic inflammation.

Impact of Oral-Cecal Transit Time on the Interpretation of Lactulose Breath Tests After RYGB: a Personalized Approach to the Diagnosis of SIBO.

Traditionally, small intestinal bacterial overgrowth (SIBO) is diagnosed when there is an early peak in breath hydrogen or methane. Given unclear intestinal transit time in Roux-en-Y gastric bypass (RYGB) patients, it is unknown if the traditional approach at diagnosing SIBO is adequate in this patient population. To assess oral-cecal transit time (OCTT) and its impact on the interpretation of breath tests in the diagnosis of SIBO in patients with RYGB. This study was a retrospective review of prospectively collected data on RYGB patients who underwent testing for SIBO using lactulose breath test (LBT) with or without small bowel follow-through (SBFT) to assess OCTT. Outcomes of SIBO test based on LBT alone versus LBT with OCTT were compared using a chi-squared test. Sixty-two of the 151 RYGB patients who underwent LBT underwent an additional SBFT to assess OCTT. Median OCTT was 60min. Of these, 59.7% had OCTT shorter than 90min. Based on LBT alone, 36/62 patients (58.1%) were classified as positive SIBO. When LBT results were combined with OCTT, 26/36 patients (72.2%) had hydrogen or methane rise within OCTT, suggesting 27.8% false positive rate. Patients with true positive SIBO based on LBT and OCTT had a higher response rate to antibiotics compared to those with false positive SIBO (78.3% vs. 33.3%, p = 0.03). A personalized approach of combining LBT with SBFT to assess OCTT may improve the accuracy of SIBO testing and enhance clinical outcomes in patients with RYGB.

Impact of Oral-Cecal Transit Time on the Interpretation of Breath Tests After RYGB: A Personalized Approach to the Diagnosis of SIBO

Introduction: Traditionally, small intestinal bacterial overgrowth (SIBO) is diagnosed when there is an early peak in breath hydrogen or methane. Given unclear intestinal transit time in Roux-en-Y gastric bypass (RYGB) patients, it is unknown if the traditional approach at diagnosing SIBO is adequate in this patient population. This study aims to assess oral-cecal transit time (OCTT) and its impact on the interpretation of breath tests in the diagnosis of SIBO in patients with RYGB. Methods: This study consisted of prospectively collected cohort of RYGB patients who underwent testing for SIBO using lactulose breath test (LBT) with or without small bowel follow-through (SBFT) to assess OCTT. Outcomes of SIBO test based on LBT alone versus LBT with OCTT were compared using a Chi-squared test. Results: 151 RYGB patients underwent LBT to assess for SIBO. Sixty-two of the 151 patients (41.1%) underwent SBFT to assess OCTT in addition to LBT. Median OCTT was 60 minutes. Of these, 59.7% had OCTT shorter than 90 minutes. Based on LBT alone, 36/62 patients (58.1%) were classified as positive SIBO. When LBT results were combined with OCTT, 26/36 patients (72.2%) had hydrogen or methane rise within OCTT, suggesting 27.8 % false positive rate. Patients with true positive SIBO based on LBT and OCTT had a higher response rate to antibiotics compared to those with false positive SIBO (78.3% vs 33.3%, p=0.03). Conclusion: A personalized approach of combining LBT with SBFT to assess OCTT may improve the accuracy of SIBO testing and enhance clinical outcomes in patients with RYGB.

Vagal dysfunction and small intestinal bacterial overgrowth: novel pathways to chronic inflammation in HIV.

Chronic inflammation in HIV-infected individuals drives disease progression and the development of comorbidities, despite viral suppression with combined antiretroviral therapy. Here, we sought evidence that vagal dysfunction, which occurs commonly as part of HIV-associated autonomic neuropathy, could exacerbate inflammation through gastrointestinal dysmotility, small intestinal bacterial overgrowth (SIBO), and alterations in patterns of soluble immune mediators. This is a cross-sectional observational study. Forty participants on stable combined antiretroviral therapy with gastrointestinal symptoms, and no causes for vagal or gastrointestinal dysfunction other than HIV, underwent autonomic testing, hydrogen/methane breath testing for SIBO, and gastric emptying scintigraphy. A panel of 41 cytokines, high-mobility group box 1, and markers of bacterial translocation (lipopolysaccharide) and monocyte/macrophage activation (sCD14 and sCD163) were tested in plasma. We found that participants with vagal dysfunction had delayed gastric emptying and higher prevalence of SIBO. SIBO was associated with IL-6, but not sCD14; lipopolysaccharide could not be detected in any participant. We also found alteration of cytokine networks in participants with vagal dysfunction, with stronger and more numerous positive correlations between cytokines. In the vagal dysfunction group, high mobility group box 1 was the only soluble mediator displaying strong negative correlations with other cytokines, especially those cytokines that had numerous other strong positive correlations. The current study provides evidence that the vagal component of HIV-associated autonomic neuropathy is associated with changes in immune and gastrointestinal function in individuals with well treated HIV. Further study will be needed to understand whether therapies targeted at enhancing vagal function could be of benefit in HIV.

Value of lactulose hydrogen breath test combined with radionuclide imaging in the diagnosis of small intestinal bacterial overgrowth

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

Meta-analysis: proton pump inhibitors moderately increase the risk of small intestinal bacterial overgrowth.

The use of proton pump inhibitors (PPIs) may potentially predispose to the development of small intestinal bacterial overgrowth (SIBO), but this association is controversial due to conflicting results from studies conducted to date. The aim of this meta-analysis was to evaluate the association between the use of PPIs and the risk of SIBO. We systematically searched the online PubMed, Embase, and Cochrane Library databases and Web of Science for relevant articles published up to November 2016. Two researchers identified and extracted data independent of each other. The pooled analysis was performed using the generic inverse-variance random-effects model. Subgroup and sensitivity analysis were conducted to assess the stability and heterogeneity of the pooled results. The risk of publication bias was evaluated by assessing for funnel plot asymmetry and by Egger's test and Begg's test. A total of 19 articles met the eligibility criteria for the meta-analysis, reporting on 7055 subjects. The pooled odds ratio (OR) showed a statistically significant association between increased risk of SIBO and PPI use (OR 1.71, 95% confidence interval 1.20-2.43). Subgroup analyses demonstrated an association between SIBO and PPI use in studies that employed small bowel aspirates culture and glucose hydrogen breath tests (GHBT) as diagnostic tests for SIBO. Our meta-analysis suggests that the use of PPI moderately increases the risk of SIBO, thereby highlighting the need for appropriate prescribing of PPIs.