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Intestinal bacterial, fungal, and methanogen overgrowth
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Background
Proton pump inhibitor (PPI) use is extremely common. PPIs have been suggested to affect the gut microbiome, and increase risks of Clostridium difficile infection and small intestinal bacterial overgrowth (SIBO). However, existing data are based on stool analyses and PPIs act on the foregut.AimsTo compare the duodenal and stool microbiomes in PPI and non-PPI users.Methods
Consecutive subjects presenting for upper endoscopy without colonoscopy were recruited. Current antibiotic users were excluded. Subjects taking PPI were age- and gender-matched 1:2 to non-PPI controls. Subjects completed medical history questionnaires, and duodenal aspirates were collected using a validated protected catheter. A subset also provided stool samples. Duodenal and stool microbiomes were analyzed by 16S rRNA sequencing.ResultsThe duodenal microbiome exhibited no phylum-level differences between PPI (N = 59) and non-PPI subjects (N = 118), but demonstrated significantly higher relative abundances of families Campylobacteraceae (3.13-fold, FDR P value < 0.01) and Bifidobacteriaceae (2.9-fold, FDR P value < 0.01), and lower relative abundance of Clostridiaceae (88.24-fold, FDR P value < 0.0001), in PPI subjects. SIBO rates were not significantly different between groups, whether defined by culture (> 103 CFU/ml) or 16S sequencing, nor between subjects taking different PPIs. The stool microbiome exhibited significantly higher abundance of family Streptococcaceae (2.14-fold, P = 0.003), and lower Clostridiaceae (2.60-fold, FDR P value = 8.61E-13), in PPI (N = 22) versus non-PPI (N = 47) subjects.Conclusions
These findings suggest that PPI use is not associated with higher rates of SIBO. Relative abundance of Clostridiaceae was reduced in both the duodenal and stool microbiomes, and Streptococcaceae was increased in stool. The clinical implications of these findings are unknown.
SIBO and SIFO are increasingly recognized as common causes of unexplained abdominal bloating, gas, distension, belching, and diarrhea. However, they are poorly recognized because of a lack of standardized diagnostic methods. Although noninvasive breath tests are often used as the first step in SIBO diagnosis, they either lack sensitivity or specificity and require further standardization and validation. Small-bowel aspirate/culture is generally accepted as the best diagnostic method, but it is invasive and is performed if symptoms are recurrent or refectory. Importantly, there is inadequate knowledge regarding the tools needed, the use of aseptic technique, and a standardized technique for collecting the small-bowel juice. Here, we describe our method of performing small-bowel aspiration to facilitate an optimal diagnosis of SIBO or SIFO (Video 1).
Background
Duodenal aspiration (DA) and lactulose breath tests (LBT) are commonly performed to diagnose small intestinal bacterial overgrowth (SIBO). There are no data directly comparing these tests.AimsTo investigate the agreement between DA and LBT for the diagnosis of SIBO.MethodsA retrospective cohort study of adult patients who underwent a LBT and a DA at a tertiary care center over 9 years was assembled. LBT was considered positive if the hydrogen baseline or peak change measurement was ≥ 20 ppm, and/or if the methane baseline or peak change was ≥ 10 ppm. DA was considered positive if > 100,000 cfu/mL of gram-negative flora was identified on culture, and contaminated if > 100,000 cfu/mL of gram-positive flora was identified.ResultsA total of 106 patients were evaluated; 81 (76.4%) were female; the mean age was 53.4 ± 15.9 years. 21 patients (19.8%) had evidence of contamination on DA. 14 (16.5%) patients had a positive DA result. Patients with diabetes mellitus and those with PPI use were more likely to have a positive DA (94.4% vs. 71.4%, p = 0.007; 62% vs. 28.6%, p = 0.021, respectively). 33 (31.1%) patients had a positive LBT. Patients with a history of small bowel resection were more likely to have a positive LBT (12.1% vs. 1.4%, p = 0.016). DA and LBT results agreed in 54 patients (63.5%; kappa = − 0.02), indicating poor agreement.Conclusions
The agreement between LBT and DA in evaluation for SIBO was poor. LBT may be favorable to DA, as LBT is safer, cheaper, and less likely to yield a contaminant result.
Small intestinal bacterial overgrowth (SIBO) is highly prevalent and is associated with numerous gastrointestinal disorders, but the microbes involved remain poorly defined. Moreover, existing studies of microbiome alterations in SIBO have utilized stool samples, which are not representative of the entire gastrointestinal tract. Therefore, we aimed to determine and compare the duodenal microbiome composition in SIBO and non-SIBO subjects, using duodenal aspirates from subjects undergoing standard-of-care esophagogastroduodenoscopy without colon preparation. Using the recently-redefined cutoff for SIBO of >103 colony forming units per milliliter (CFU/mL), 42 SIBO and 98 non-SIBO subjects were identified. Duodenal samples from SIBO subjects had 4x103-fold higher counts than non-SIBO subjects when plated on MacConkey agar (P
Purpose of review
The goal of this paper is to review categorically treatment options for the diverse mechanisms to which studies have shown underlie bloating and abdominal distension.
Recent findings
While previous studies typically associate bloating and distension with a functional gastrointestinal disorder, in appropriate clinical settings, workup to look at diseases such as postural orthostatic hypotension, chronic intestinal pseudoobstruction, Ehlers-Danlos syndrome, and mast cell activation syndrome can further provide insight into to these patients.
Summary
Bloating and distension are commonly presented to the gastroenterologist. The underlying mechanism can be ambiguous, and therefore, the treatment can be challenging. However, current treatment options that are available can be effective if used in the appropriate patient. Further research is desperately needed for the more elusive disease processes mentioned in this review that presents with bloating and distension.
Constipation is the most common adverse event (AE) of opioid therapy. This multicenter, phase 2 study evaluated the efficacy and safety of linaclotide in treating opioid-induced constipation (OIC) in patients with chronic noncancer pain syndromes (NCT02270983). Adults with OIC (<3 spontaneous bowel movements [SBMs]/week) related to chronic noncancer pain were randomized 1:1:1 to receive linaclotide 145 µg, linaclotide 290 µg, or placebo once daily for 8 weeks. The primary endpoint was change from baseline in 8-week SBM frequency rate (SBMs/week). Secondary efficacy endpoints included 6/8-week SBM 3 + 1 responders, time to first SBM, and changes from baseline in 8-week stool consistency, abdominal bloating, and straining. Additional endpoints included treatment satisfaction and adequate relief responders. In total, 254 patients were randomized: 87, 88, and 79 received linaclotide 145 µg, linaclotide 290 µg, and placebo, respectively. The mean changes from baseline in SBMs/week during the treatment period were 2.9 and 3.5 in the linaclotide 145 and 290 µg groups (P < 0.01 for both doses), respectively, vs 1.6 in the placebo group. Diarrhea, the most common AE, was generally mild, resulting in 1.1%, 5.7%, and 1.3% of patients discontinuing in the linaclotide 145 μg, linaclotide 290 μg, and placebo groups, respectively. No serious AEs related to diarrhea were reported in any treatment group. Compared with placebo, linaclotide-treated patients had significant improvements in stool consistency, straining, abdominal bloating, and treatment satisfaction scores (P < 0.05). Linaclotide significantly improved OIC symptoms and was well tolerated in patients with chronic noncancer pain.
Background
Most gut microbiome studies have been performed using stool samples. However, the small intestine is of central importance to digestion, nutrient absorption, and immune function, and characterizing its microbial populations is essential for elucidating their roles in human health and disease.AimsTo characterize the microbial populations of different small intestinal segments and contrast these to the stool microbiome.Methods
Male and female subjects undergoing esophagogastroduodenoscopy without colon preparation were prospectively recruited. Luminal aspirates were obtained from the duodenum, jejunum, and farthest distance reached. A subset also provided stool samples. 16S rRNA sequencing was performed and analyses were carried out using CLC Genomics Workbench.Results16S rRNA sequencing identified differences in more than 2000 operational taxonomic units between the small intestinal and stool microbiomes. Firmicutes and Proteobacteria were the most abundant phyla in the small intestine, and Bacteroidetes were less abundant. In the small intestine, phylum Firmicutes was primarily represented by lactic acid bacteria, including families Streptococcaceae, Lactobacillaceae, and Carnobacteriaceae, and Proteobacteria was represented by families Neisseriaceae, Pasteurellaceae, and Enterobacteriaceae. The duodenal and FD microbial signatures were markedly different from each other, but there were overlaps between duodenal and jejunal and between jejunal and FD microbial signatures. In stool, Firmicutes were represented by families Ruminococcaceae, Lachnospiraceae, Christensenellaceae, and Proteobacteria by class Deltaproteobacteria.Conclusions
The small bowel microbiome is markedly different from that in stool and also varies between segments. These findings may be important in determining how compositional changes in small intestinal microbiota contribute to human disease states.
Introduction
Breath testing (BT) has gained interest for diagnosing small intestinal bacterial overgrowth (SIBO) in IBD patients with irritable bowel syndrome (IBS) overlap. We aim to characterize the rate of SIBO and BT gas patterns in IBD patients with IBS-like symptoms compared to non-IBD patients.
Methods
A database of 14,847 consecutive lactulose BTs was developed from patients with IBS-like symptoms between November 2005 and October 2013. BTs were classified as normal, H2 predominant, CH4 predominant, and flatline based on criteria established from the literature. BT data linkage with electronic health records and chart review identified IBD patients along with disease phenotype, location, severity, and antibiotic response. Poisson loglinear model evaluated differences in gas patterns between the two groups.
Results
After excluding patients with repeat breath tests, we identified 486 IBD and 10,505 non-IBD patients with at least one BT. Positive BT was present in 57% (n = 264) of IBD patients. Crohn’s disease (odds ratio (OR) 0.21, [95% confidence interval (CI) 0.11–0.38]) and ulcerative colitis (OR 0.39, [95% CI 0.22–0.70]) patients were less likely to produce excess CH4. IBD patients were more likely to have flatline BT (OR 1.82, [95% CI 1.20–2.77]). In IBD patients with SIBO, 57% improved symptomatically with antibiotics.
Conclusion
In a cohort of IBD patients with IBS-like symptoms, a high rate of patients had positive BT and symptomatic improvement with antibiotics. In IBD, methanogenesis is suppressed and flatline BT is more frequent, suggesting excess hydrogenotrophic bacteria. These findings suggest methanogenic and hydrogenotrophic microorganisms as potential targets for microbiome-driven biomarkers and therapies.
Objectives:
The nonsystemic antibiotic rifaximin is indicated for irritable bowel syndrome with diarrhea (IBS-D) in adults; however, determinants of response remain unclear. The utility of lactulose breath testing (LBT) in predicting response to rifaximin was examined.
Methods:
Adults with IBS-D received open-label rifaximin 550 mg 3 times daily for 2 weeks, followed by a 4-week posttreatment assessment period. Thirteen centers prospectively participated in this substudy. LBT was conducted before (day 1) and after (day 14) therapy (breath samples obtained every 15 minutes; up to 240 minutes). Patient response (decrease from baseline of ≥30% in abdominal pain and ≥50% decrease in frequency of mushy/watery stool), symptom improvement, and the relationship of clinical outcomes to LBT results were assessed.
Results:
A total of 93 patients were included; 62 (66.7%) had positive baseline LBT results. Overall, 48.4% (45/93) of patients responded to rifaximin; of these, 59.7% (37/62) had a positive baseline LBT vs 25.8% (8/31) with a negative LBT (P = 0.002; odds ratio 4.3, 95% confidence interval, 1.5-12.7). Patients with a positive baseline LBT result experienced significantly greater improvement from baseline in 6 of 7 individual IBS symptoms. LBT results after rifaximin therapy did not correlate with clinical response in the 86 patients with evaluable breath tests (P = 0.21); however, patients whose LBT results normalized after rifaximin had the highest response rate of 76.5% (13/17).
Discussion:
A positive baseline LBT result predicted a higher likelihood of response to rifaximin in IBS-D, suggesting a gut microbiome modulatory mechanism of action for rifaximin.
Background:
The human small intestine plays a central role in the processes of digestion and nutrient absorption. However, characterizations of the human gut microbiome have largely relied on stool samples, and the associated methodologies are ill-suited for the viscosity and low microbial biomass of small intestine samples. As part of the REIMAGINE study to examine the specific roles of the small bowel microbiome in human health and disease, this study aimed to develop and validate methodologies to optimize microbial analysis of the small intestine.
Results:
Subjects undergoing esophagogastroduodenoscopy without colon preparation for standard of care were prospectively recruited, and ~ 2 ml samples of luminal fluid were obtained from the duodenum using a custom sterile aspiration catheter. Samples of duodenal aspirates were either untreated (DA-U, N = 127) or pretreated with dithiothreitol (DA-DTT, N = 101), then cultured on MacConkey agar for quantitation of aerobic gram-negative bacteria, typically from the class Gammaproteobacteria, and on blood agar for quantitation of anaerobic microorganisms. DA-DTT exhibited 2.86-fold greater anaerobic bacterial counts compared to DA-U (P = 0.0101), but were not statistically different on MacConkey agar. DNA isolation from DA-U (N = 112) and DA-DTT (N = 43) samples and library preparation for 16S rRNA gene sequencing were also performed using modified protocols. DA-DTT samples exhibited 3.81-fold higher DNA concentrations (P = 0.0014) and 4.18-fold higher 16S library concentrations (P < 0.0001) then DA-U samples. 16S rRNA gene sequencing revealed increases in the detected relative abundances of obligate and facultative anaerobes in DA-DTT samples, including increases in the genera Clostridium (false discovery rate (FDR) P = 4.38E-6), Enterococcus (FDR P = 2.57E-8), Fusobacterium (FDR P = 0.02) and Bacteroides (FDR P = 5.43E-9). Detected levels of Gram-negative enteropathogens from the phylum Proteobacteria, such as Klebsiella (FDR P = 2.73E-6) and Providencia (FDR P < 0.0001) (family Enterobacteriaceae) and Pseudomonas (family Pseudomonadaceae) (FDR P = 0.04), were also increased in DA-DTT samples.
Conclusions:
This study validates novel DTT-based methodology which optimizes microbial culture and 16S rRNA gene sequencing for the study of the small bowel microbiome. The microbial analyses indicate increased isolation of facultative and obligate anaerobes from the mucus layer using these novel techniques.
Background
Unexplained bloating, gas, and pain are common symptoms. If routine tests are negative, such patients are often labeled as irritable bowel syndrome.
Aims
To determine the diagnostic utility of breath tests that assess for small intestinal bacterial overgrowth (SIBO), fructose or lactose intolerance, and the predictive value of symptoms.
Methods
Patients with gas, bloating, diarrhea, abdominal pain (≥ 6 months), and negative endoscopy and radiology tests were assessed with symptom questionnaires, glucose (75 g), fructose (25 g), or lactose (25 g) breath tests. Breath tests were categorized as positive when H2 (≥ 20 ppm) or CH4 (≥ 15 ppm) increased above baseline values or as hypersensitive when symptoms changed significantly without rise in H2/CH4 or as negative.
Results
1230 patients (females = 878) underwent 2236 breath tests. The prevalence of SIBO was 33% (294/883), fructose intolerance was 34% (262/763), and lactose intolerance was 44% (260/590). Hypersensitivity was found in 16% and 9%, respectively, during fructose and lactose breath tests. Although gas (89%), abdominal pain (82%), and bloating (82%) were highly prevalent, pretest symptoms or their severity did not predict an abnormal breath test, but symptoms during the breath test facilitated diagnosis of SIBO, fructose, and lactose intolerance and hypersensitivity.
Conclusions
Approximately 45% of patients with unexplained gas and bloating had SIBO, fructose, or lactose intolerance; another 9–16% had visceral hypersensitivity. Pretest symptoms were poor predictors, but symptoms during the breath tests were useful. Breath tests are safe, provide significant diagnostic yield, and could be useful in routine gastroenterology practice.
Small intestinal bacterial overgrowth (SIBO) is a common, yet underrecognized, problem. Its prevalence is unknown because SIBO requires diagnostic testing. Although abdominal bloating, gas, distension, and diarrhea are common symptoms, they do not predict positive diagnosis. Predisposing factors include proton-pump inhibitors, opioids, gastric bypass, colectomy, and dysmotility. Small bowel aspirate/culture with growth of 10-10 cfu/mL is generally accepted as the "best diagnostic method," but it is invasive. Glucose or lactulose breath testing is noninvasive but an indirect method that requires further standardization and validation for SIBO. Treatment, usually with antibiotics, aims to provide symptom relief through eradication of bacteria in the small intestine. Limited numbers of controlled studies have shown systemic antibiotics (norfloxacin and metronidazole) to be efficacious. However, 15 studies have shown rifaximin, a nonsystemic antibiotic, to be effective against SIBO and well tolerated. Through improved awareness and scientific rigor, the SIBO landscape is poised for transformation.
Inflammatory bowel diseases (IBD), Crohn`s disease and ulcerative colitis, are chronic conditions associated with high morbidity and healthcare costs. The natural history of IBD is variable and marked by alternating periods of flare and remission. Even though the use of newer therapeutic targets has been associated with higher rates of mucosal healing, a great proportion of IBD patients remain symptomatic despite effective control of inflammation. These symptoms may include but not limited to abdominal pain, dyspepsia, diarrhea, urgency, fecal incontinence, constipation or bloating. In this setting, commonly there is an overlap with gastrointestinal (GI) motility and absorptive disorders. Early recognition of these conditions greatly improves patient care and may decrease the risk of mistreatment. Therefore, in this review we describe the prevalence, diagnosis and treatment of GI motility and absorptive disorders that commonly affect patients with IBD.
Background and aim:
Opioid induced constipation (OIC) is the most common side effect of opioid therapy. It can lead to a decreased quality of life. Naldemedine is a peripherally acting μ-opioid receptor antagonist that has been recently studied in randomized controlled trials (RCTs) for the management of OIC. The aim of this study is to perform a meta-analysis of existing clinical trials to estimate the efficacy and safety of naldemedine in opioid-induced constipation.
Methods:
A systematic search of PubMed, CINAHL, Scopus, Cochrane database of systematic reviews, and ClinicalTrials.gov registry was performed in March 2018. Two independent reviewers systematically identified prospective RCTs published in the English language that compared the effect of oral naldemedine versus placebo in adults with OIC. Meta-analysis was performed using a random effects model to assess the primary outcome: spontaneous bowel movement (SBM) responder rates. Assessed secondary outcomes were: a change in SBM frequency per week from baseline during the treatment period, change from baseline in the frequency of complete SBM and incidence of treatment-emergent adverse events. Review Manager 5.3 software program was utilized for statistical analysis.
Results:
Six RCTs met the inclusion criteria. A total of 2,762 patients were included in the meta-analysis. The proportion of SBM responders was significantly higher in the naldemedine group compared to the placebo group (56.4%, vs. 34.7%, p<0.00001). There was no statistically significant difference in treatment-emergent adverse events between naldemedine group and placebo group (mean odds ratio=1.18, p = 0.25, 95% CI: 0.89-1.55). Change in SBM frequency was higher in the naldemedine group versus placebo group (p<0.00001), as well as the change in complete SBM frequency.
Conclusions:
Naldemedine 0.2 mg daily significantly improved symptoms in patients with opioid-induced constipation and was generally well tolerated. These results support the use of naldemedine for the treatment of opioid-induced constipation.
Objective:
To systematically review the effects of soft tissue mobilization (STM) on both surgical and non-surgical abdominal adhesion-related symptoms.
Study design:
Systematic Review.
Background:
It is known that abdominal adhesions can cause a variety of symptoms with one of the most common being abdominal pain. To date, there is no known systematic review that documents the effects of STM on adhesion-related abdominal symptoms.
Methods and measures:
A systematic review of literature was indexed in the following databases: PubMed, Cochrane, Google Scholar, OVID, and EBSCO. The quality of the studies was assessed using the MINORS scale.
Results:
Nine studies satisfied the eligibility criteria for this systematic review. The studies' population age ranged from 10.7 to 89.4 years. Four articles were nonrandomized and had scores ranging from 3 to 14 out of 16 total on the MINORS scale. Five articles were randomized controlled trials or comparative studies and scores ranged from 16 to 23 out of 24 total on the MINORS scale. There were five articles that used pain as an objective measure and all of them reported a decrease in pain after treatment. Two studies looked at quality of life and function and both saw objective improvements following abdominal adhesion treatment. Collectively, there were also improvements seen in scar mobility, infertility, posture, a reduction in medication, increased pressure tolerance and decreased postoperative ileus.
Conclusion:
The results of this review indicate preliminary strong evidence for the benefits of STM on symptoms relating to acute post-surgical adhesions, preliminary moderate evidence for the benefits of STM on symptoms relating to chronic non-surgical related adhesions (fertility and SBO) and moderate evidence for the benefits of STM on symptoms relating to chronic post-surgical adhesions.
Background:
D-lactic acidosis is characterized by brain fogginess (BF) and elevated D-lactate and occurs in short bowel syndrome. Whether it occurs in patients with an intact gut and unexplained gas and bloating is unknown. We aimed to determine if BF, gas and bloating is associated with D-lactic acidosis and small intestinal bacterial overgrowth (SIBO).
Methods:
Patients with gas, bloating, BF, intact gut, and negative endoscopic and radiological tests, and those without BF were evaluated. SIBO was assessed with glucose breath test (GBT) and duodenal aspiration/culture. Metabolic assessments included urinary D-lactic acid and blood L-lactic acid, and ammonia levels. Bowel symptoms, and gastrointestinal transit were assessed.
Results:
Thirty patients with BF and 8 without BF were evaluated. Abdominal bloating, pain, distension and gas were the most severe symptoms and their prevalence was similar between groups. In BF group, all consumed probiotics. SIBO was more prevalent in BF than non-BF group (68 vs. 28%, p = 0.05). D-lactic acidosis was more prevalent in BF compared to non-BF group (77 vs. 25%, p = 0.006). BF was reproduced in 20/30 (66%) patients. Gastrointestinal transit was slow in 10/30 (33%) patients with BF and 2/8 (25%) without. Other metabolic tests were unremarkable. After discontinuation of probiotics and a course of antibiotics, BF resolved and gastrointestinal symptoms improved significantly (p = 0.005) in 23/30 (77%).
Conclusions:
We describe a syndrome of BF, gas and bloating, possibly related to probiotic use, SIBO, and D-lactic acidosis in a cohort without short bowel. Patients with BF exhibited higher prevalence of SIBO and D-lactic acidosis. Symptoms improved with antibiotics and stopping probiotics. Clinicians should recognize and treat this condition.
Background:
Small intestinal bacterial overgrowth (SIBO) may cause symptoms in patients with abdominal bloating, distension, and gas. SIBO can be assessed using the lactulose breath test (LBT). A commonly used probiotic supplement is Align containing Bifidobacterium infantis 35624. The aim of this study was to determine the effect of B. infantis 35624 on hydrogen and methane excretion during LBT.
Methods:
Healthy subjects underwent LBT before and after 2 weeks of daily Align administration. Hydrogen and methane concentrations were measured for each breath sample. Results are expressed as mean ± SE and analyzed using repeated measures ANCOVA. A breath test was considered positive if hydrogen and/or methane increased > 20 ppm above baseline by 90 min of the test or if a dual hydrogen peak was present.
Results:
Nineteen healthy subjects were studied. Hydrogen levels were similar pre- and post-probiotic across the 3-h study (p = 0.768). In contrast, methane levels were significantly higher with probiotic administration (p = 0.012). A rise in methane > 20 ppm was seen in three subjects pre-probiotic but six post-probiotic. Of the 19 subjects, an "abnormal" LBT pre-probiotic was present in ten subjects and during the probiotic, 13 were abnormal.
Conclusions:
This study found that 2 weeks of B. infantis 35624 (Align) supplementation affects LBT assessment for SIBO by significantly increasing methane, but not hydrogen, excretion after lactulose administration. Methane levels reached values that would be considered positive for SIBO patients. This study suggests that patients undergoing LBT should discontinue probiotics prior to the test as these supplements may alter the test results.
Background:
Fecal microbiota transplantation (FMT) is safe and effective for recurrent Clostridium difficile infection (rCDI) and often involves terminal ileal (TI) stool infusion. Patients report gastrointestinal (GI) symptoms post-FMT despite rCDI resolution. Small intestinal bacterial overgrowth (SIBO) screening is not routinely performed pre-FMT. The effect of donor/recipient SIBO status on FMT outcomes and post-FMT GI symptoms is unclear. We aim to evaluate the value of pre-FMT SIBO screening on post-FMT outcomes and symptoms.
Methods:
This was a prospective pilot study of consecutive adults with rCDI undergoing FMT by colonoscopy at a tertiary center. Routine pre-FMT screening and baseline lactulose breath tests (LBTs) were performed for donors and recipients. Positive LBT required a rise > 20 ppm in breath hydrogen or any methane level > 10 ppm within 90 min. The presence of GI symptoms and CDI resolution were assessed 8 weeks post-FMT. Fisher's exact/Student's t tests were performed for statistical analyses.
Results:
Twenty recipients (58.3 years, 85% women) enrolled in the study. Fourteen (70%) FMTs involved TI stool infusion. Four (20%) recipients and six (30%) donors had positive LBT pre-FMT. At 8 weeks post-FMT, 17 (85%) recipients had CDI resolution and five (25%) reported GI symptoms. Pre-FMT LBT result was not associated with post-FMT CDI resolution or GI symptoms. There was a trend toward increased GI symptoms among recipients receiving stool from LBT-positive donors (50 vs 14.2%, p = 0.09).
Conclusions:
FMT is effective and well tolerated for rCDI. Positive LBT in asymptomatic donors may have an effect on post-FMT GI symptoms. Larger studies are needed.
Objectives:
Breath tests (BTs) are important for the diagnosis of carbohydrate maldigestion syndromes and small intestinal bacterial overgrowth (SIBO). However, standardization is lacking regarding indications for testing, test methodology and interpretation of results. A consensus meeting of experts was convened to develop guidelines for clinicians and research.
Methods:
Pre-meeting survey questions encompassing five domains; indications, preparation, performance, interpretation of results, and knowledge gaps, were sent to 17 clinician-scientists, and 10 attended a live meeting. Using an evidence-based approach, 28 statements were finalized and voted on anonymously by a working group of specialists.
Results:
Consensus was reached on 26 statements encompassing all five domains. Consensus doses for lactulose, glucose, fructose and lactose BT were 10, 75, 25 and 25 g, respectively. Glucose and lactulose BTs remain the least invasive alternatives to diagnose SIBO. BT is useful in the diagnosis of carbohydrate maldigestion, methane-associated constipation, and evaluation of bloating/gas but not in the assessment of oro-cecal transit. A rise in hydrogen of ≥20 p.p.m. by 90 min during glucose or lactulose BT for SIBO was considered positive. Methane levels ≥10 p.p.m. was considered methane-positive. SIBO should be excluded prior to BT for carbohydrate malabsorption to avoid false positives. A rise in hydrogen of ≥20 p.p.m. from baseline during BT was considered positive for maldigestion.
Conclusions:
BT is a useful, inexpensive, simple and safe diagnostic test in the evaluation of common gastroenterology problems. These consensus statements should help to standardize the indications, preparation, performance and interpretation of BT in clinical practice and research.Am J Gastroenterol advance online publication, 21 March 2017; doi:10.1038/ajg.2017.46.
Background and aims:
Few treatments have demonstrated efficacy and safety for diarrhea-predominant irritable bowel syndrome (IBS-D). A phase 3, randomized, double-blind, placebo-controlled trial was performed to evaluate the safety and efficacy of repeat treatment with the nonsystemic antibiotic rifaximin.
Methods:
The trial included adults with IBS-D, mean abdominal pain and bloating scores of 3 or more, and loose stool, located at 270 centers in the United States and Europe from February 2012 through June 2014. Those responding to a 2 week course of open-label rifaximin 550 mg 3 times daily who then relapsed during an observation phase (up to 18 weeks) were randomly assigned to groups given repeat treatments of rifaximin 550 mg or placebo, 3 times daily for 2 weeks. The primary endpoint was percentage of responders after first repeat treatment, defined as a decrease in abdominal pain of 30% or more from baseline and a decrease in frequency of loose stools of 50% or more from baseline, for 2 or more weeks during a 4-week posttreatment period.
Results:
Of 1074 patients (44.1%) who responded to open-label rifaximin, 382 (35.6%) did not relapse, whereas 692 (64.4%) did; of these, 636 were randomly assigned to receive repeat treatment with rifaximin (n=328) or placebo (n=308). The percentage of responders was significantly greater with rifaximin than placebo (38.1% vs 31.5%, P=.03). The percentage of responders for abdominal pain (50.6% vs 42.2%, P=.018) was significantly greater with rifaximin than placebo, but not stool consistency (51.8% vs 50.0%, P=.42). Significant improvements were also noted for prevention of recurrence, durable response, and bowel movement urgency. Adverse event rates were low and similar between groups.
Conclusions:
In a phase 3 study of patients with relapsing symptoms of IBS-D, repeat rifaximin treatment was efficacious and well tolerated.
Small intestinal bacterial overgrowth (SIBO) is characterized by an excessive amount of bacteria in the small intestine and a constellation of symptoms that include bloating, pain, gas, and diarrhea. Although known for many decades, there is a lack of consensus and clarity regarding the natural history and methods for its diagnosis. Several tests have been proposed, including the glucose breath test, lactulose breath test, small intestinal aspiration and culture, and others. However, there is a lack of standardization of these tests and their interpretation. Treatment of SIBO remains empirical; generally, broad spectrum antibiotics are recommended for 2 weeks (amoxicillin, rifaximin, ciprofloxacin, etc.) but evidence for their use is fair. Clearly, there is a strong need to develop a systematic approach for the management of SIBO and to perform multicenter clinical trials for the treatment of SIBO. In this review, we will discuss the current evidence for the diagnosis and treatment of SIBO, which includes (1) elimination/modification of the underlying causes, (2) induction of remission (antibiotics and elemental diet), and (3) maintenance of remission (promotility drugs, dietary modifications, repeat or cyclical antibiotics).
Currently, six glucagon-like peptide-1 receptor agonists (GLP-1RAs) are approved for treating type 2 diabetes. These fall into two classes based on their receptor activation: short-acting exenatide twice daily (BID) and lixisenatide once daily (OD); and longer-acting liraglutide OD, exenatide once weekly (OW), albiglutide OW and dulaglutide OW. The phase 3 trial of a seventh GLP-1RA, taspoglutide OW, was stopped due to unacceptable adverse events (AEs). Nine phase 3 head-to-head trials and one large phase 2 study have compared the efficacy and safety of these seven GLP-1RAs. All trials were associated with notable reductions in HbA1c, although liraglutide led to greater decreases than exenatide formulations and albiglutide, and HbA1c reductions did not differ between liraglutide and dulaglutide. As the short-acting GLP-1RAs delay gastric emptying, they have greater effects on postprandial glucose levels than the longer-acting agents, whereas the longer-acting compounds reduced plasma glucose throughout the 24-h period studied. Liraglutide was associated with weight reductions similar to those with exenatide BID but greater than those with exenatide OW, albiglutide and dulaglutide. The most frequently observed AEs with GLP-1RAs were gastrointestinal disorders, particularly nausea, vomiting and diarrhoea; nausea, however, occurred less frequently with exenatide OW and albiglutide than exenatide BID and liraglutide. Both exenatide formulations and albiglutide may be associated with higher incidences of injection-site reactions than liraglutide and dulaglutide. GLP-1RA use in clinical practice should be customized for individual patients, based on clinical profile and patient preference. Ongoing assessments of novel GLP-1RAs and delivery methods may further expand future treatment options.
Parkinson's disease (PD) is characterized by alphasynucleinopathy that affects all levels of the braingut axis including the central, autonomic, and enteric nervous systems. Recently, it has been recognized that the brain-gut axis interactions are significantly modulated by the gut microbiota via immunological, neuroendocrine, and direct neural mechanisms. Dysregulation of the brain-gut-microbiota axis in PD may be associated with gastrointestinal manifestations frequently preceding motor symptoms, as well as with the pathogenesis of PD itself, supporting the hypothesis that the pathological process is spread from the gut to the brain. Excessive stimulation of the innate immune system resulting from gut dysbiosis and/or small intestinal bacterial overgrowth and increased intestinal permeability may induce systemic inflammation, while activation of enteric neurons and enteric glial cells may contribute to the initiation of alpha-synuclein misfolding. Additionally, the adaptive immune system may be disturbed by bacterial proteins cross-reacting with human antigens. A better understanding of the brain-gutmicrobiota axis interactions should bring a new insight in the pathophysiology of PD and permit an earlier diagnosis with a focus on peripheral biomarkers within the enteric nervous system. Novel therapeutic options aimed at modifying the gut microbiota composition and enhancing the intestinal epithelial barrier integrity in PD patients could influence the initial step of the following cascade of neurodegeneration in PD.
Objective A low FODMAP (Fermentable Oligosaccharides, Disaccharides, Monosaccharides And Polyols) diet reduces symptoms of IBS, but reduction of potential prebiotic and fermentative effects might adversely affect the colonic microenvironment. The effects of a low FODMAP diet with a typical Australian diet on biomarkers of colonic health were compared in a single-blinded, randomised, cross-over trial.
Design Twenty-seven IBS and six healthy subjects were randomly allocated one of two 21-day provided diets, differing only in FODMAP content (mean (95% CI) low 3.05 (1.86 to 4.25) g/day vs Australian 23.7 (16.9 to 30.6) g/day), and then crossed over to the other diet with ≥21-day washout period. Faeces passed over a 5-day run-in on their habitual diet and from day 17 to day 21 of the interventional diets were pooled, and pH, short-chain fatty acid concentrations and bacterial abundance and diversity were assessed.
Results Faecal indices were similar in IBS and healthy subjects during habitual diets. The low FODMAP diet was associated with higher faecal pH (7.37 (7.23 to 7.51) vs 7.16 (7.02 to 7.30); p=0.001), similar short-chain fatty acid concentrations, greater microbial diversity and reduced total bacterial abundance (9.63 (9.53 to 9.73) vs 9.83 (9.72 to 9.93) log10 copies/g; p<0.001) compared with the Australian diet. To indicate direction of change, in comparison with the habitual diet the low FODMAP diet reduced total bacterial abundance and the typical Australian diet increased relative abundance for butyrate-producing Clostridium cluster XIVa (median ratio 6.62; p<0.001) and mucus-associated Akkermansia muciniphila (19.3; p<0.001), and reduced Ruminococcus torques.
Conclusions Diets differing in FODMAP content have marked effects on gut microbiota composition. The implications of long-term reduction of intake of FODMAPs require elucidation.
Trial registration number ACTRN12612001185853.
Background
Clinical trials in irritable bowel syndrome are associated with high placebo response rates. We aimed to identify the magnitude of the placebo response and the contributing factors to this occurrence.
Methods
We did a systematic review and meta-analysis with a search of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials between April 1, 1959, and April 30, 2020. We included all randomised controlled trials that compared an active pharmacotherapeutic agent with placebo and had a dichotomous outcome of response to therapy (in terms of global improvement or improvement in abdominal pain) in adults (aged ≥18 years) with irritable bowel syndrome. Exclusion criteria were trials reporting on treatment satisfaction as a dichotomous outcome of response to therapy or clinician-reported outcomes and a treatment duration of less than 4 weeks. Our main outcome was identification of the magnitude of the pooled placebo response rate for the following endpoints: global improvement, abdominal pain, and US Food and Drug Administration (FDA) endpoints. We extracted information from published reports and pooled proportions through meta-analysis with random effects. The study was registered with PROSPERO, CRD42020170908.
Findings
Of the 6863 publications identified, 70 articles describing 73 randomised controlled trials were included in our analysis. The pooled placebo response rate was 27·3% (95% CI 24·3–30·9) using the global improvement endpoint, 34·4% (31·2–37·8) using the abdominal pain endpoint, and 17·9% (15·2–21·0) using the composite FDA endpoint responder definition, all with substantial heterogeneity between the trials. Studies published before 2006, and those done in Europe, with a parallel design, a run-in period of 2 weeks or less, a dose schedule of three times a day or more, or a smaller sample size of the control group were significantly associated with an increased pooled placebo response rate.
Interpretation
More than a quarter of patients with irritable bowel syndrome had a placebo response in terms of global improvement, with multiple associated moderators. We recommend future trials apply a run-in period of at least 2 weeks and dose once or twice a day to minimise the placebo response rate.
Funding
None.
Irritable bowel syndrome (IBS) is a highly prevalent, chronic disorder that significantly reduces patients' quality of life. Advances in diagnostic testing and in therapeutic options for patients with IBS led to the development of this first-ever American College of Gastroenterology clinical guideline for the management of IBS using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Twenty-five clinically important questions were assessed after a comprehensive literature search; 9 questions focused on diagnostic testing; 16 questions focused on therapeutic options. Consensus was obtained using a modified Delphi approach, and based on GRADE methodology, we endorse the following: We suggest that a positive diagnostic strategy as compared to a diagnostic strategy of exclusion be used to improve time to initiating appropriate therapy. We suggest that serologic testing be performed to rule out celiac disease in patients with IBS and diarrhea symptoms. We suggest that fecal calprotectin be checked in patients with suspected IBS and diarrhea symptoms to rule out inflammatory bowel disease. We recommend a limited trial of a low fermentable oligosaccharides, disacchardies, monosaccharides, polyols (FODMAP) diet in patients with IBS to improve global symptoms. We recommend the use of chloride channel activators and guanylate cyclase activators to treat global IBS with constipation symptoms. We recommend the use of rifaximin to treat global IBS with diarrhea symptoms. We suggest that gut-directed psychotherapy be used to treat global IBS symptoms. Additional statements and information regarding diagnostic strategies, specific drugs, doses, and duration of therapy can be found in the guideline.
Abstract
Background: Recent data substantiate the importance of acute gastroenteritis in the
development of irritable bowel syndrome (IBS). An animal model of postinfectious
IBS determined the importance of cytolethal distending toxin B (CdtB) during live
Campylobacter jejuni infection and its development of autoimmunity to vinculin. In
this study, we examine whether subcutaneous exposure to CdtB alone is sufficient to
produce the postinfectious IBS effect and autoimmunity.
Methods: Sixty adult Sprague Dawley rats were randomized into 2 groups to receive
subcutaneous injection of either CdtB or vehicle and administered a booster
injection of the same product 3 weeks later. Serum was collected for anti-CdtB and
anti-vinculin titers. Duodenal and ileal luminal contents for total eubacterial qPCR,
and ileal bowel segments were harvested for vinculin and ileal expression. In a second
experiment, 4 adult, Sprague Dawley rats were injected with either Cy7-labeled
anti-CdtB and anti-vinculin antibodies were injected into the tail vein and imaged to
determine organ localization of the antibodies.
Key Results: Rats that received CdtB increased in serum anti-CdtB after injection.
CdtB exposure also precipitated significant elevation in anti-vinculin antibodies
(P < .001). This was associated with a reduction in intestinal vinculin expression
(P < .001) that negatively correlated with serum anti-CdtB levels. CdtB exposure was
also associated with greater levels of duodenal (P < .001) and ileal (P < .01) bacteria
by qPCR that positively correlated with anti-CdtB levels.
Conclusions and Inferences: Rats injected with CdtB developed a postinfectious IBSlike
phenotype and autoimmunity to vinculin with corresponding reduction in intestinal
vinculin expression.
Small intestinal bacterial overgrowth is defined as the presence of excessive numbers of bacteria in the small bowel, causing gastrointestinal symptoms. This guideline statement evaluates criteria for diagnosis, defines the optimal methods for diagnostic testing, and summarizes treatment options for small intestinal bacterial overgrowth. This guideline provides an evidence-based evaluation of the literature through the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process. In instances where the available evidence was not appropriate for a formal GRADE recommendation, key concepts were developed using expert consensus.
Introduction:
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.
Methods:
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.
Results:
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).
Discussion:
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.
INTRODUCTION
The small intestine is an understudied frontier of microbiome research. While aspiration during endoscopy is considered the gold standard to assess small bowel bacteria, the tools for sterile retrieval are primitive and poorly validated. Moreover, endoscopic aspiration is time consuming and prone to contamination. Inspired by plants’ ability to draw water via capillary action, a novel multi-capillary sterile system was designed. We examined the suctioning time and volume capabilities of this catheter using various liquids compared to conventional aspiration catheters.
METHODS
Liquids with varying viscosities (water, 25% glucose solution and povidone iodine 10%) were used to assess the aspiration efficiency of the capillary catheter (MicroLotus, Hobbs Medical Inc.) ex-vivo as compared to a conventional small bowel aspiration catheter (Hobbs Medical Inc.) (Figure 1). Viscosity ranged between 0.89 mPa*s for water to 18 mPa*s for povidone. In the first experiment, 8 ml of each liquid was placed in a test tube. Catheters were completely submerged in the liquid and suction was applied using a standardized suctioning technique (Alliance™ II Integrated Inflation device). Next, the same four liquids were placed in a petri dish to mimic the flat mucosal surface. The technique was repeated with 3mL (typical volume of small bowel aspirate). Each experiment was repeated 10 times.
RESULTS
The conventional catheter suffered from air entering the catheter when not completely submerged which is typical of the small bowel surface. In terms of speed of aspiration, the capillary catheter was at least 10 times faster than the conventional catheter for all fluid viscosities (Figure 2). Capillary catheter demonstrated increasing superiority with increasing viscosity (R = 0.96). When comparing aspiration on a flat surface, aspiration times were 4.67 + 1.35, 9.65 + 2.03 and 23.52 + 3.30 seconds for water, glucose and povidone for the capillary catheter, and too long to measure for the conventional due to concomitant superfluous air entry due to catheter design.
CONCLUSION
The capillary aspiration catheter system is superior to conventional aspiration catheter in suctioning liquids with various viscosities. This new system may improve aspiration time and quality for small bowel aspiration. Overall, this new system could save between 1 and 6 minutes in endoscopy time to obtain aspirates depending upon the viscosity of the aspirating fluid. Future in-vivo studies are needed to further assess the capillary catheter.
Small intestinal fungal overgrowth (SIFO) is characterized by the presence of excessive number of fungal organisms in the small intestine associated with gastrointestinal (GI) symptoms. Candidiasis is known to cause GI symptoms particularly in immunocompromised patients or those receiving steroids or antibiotics. However, only recently, there is emerging literature that an overgrowth of fungus in the small intestine of non-immunocompromised subjects may cause unexplained GI symptoms. Two recent studies showed that 26 % (24/94) and 25.3 % (38/150) of a series of patients with unexplained GI symptoms had SIFO. The most common symptoms observed in these patients were belching, bloating, indigestion, nausea, diarrhea, and gas. The underlying mechanism(s) that predisposes to SIFO is unclear but small intestinal dysmotility and use of proton pump inhibitors has been implicated. However, further studies are needed; both to confirm these observations and to examine the clinical relevance of fungal overgrowth, both in healthy subjects and in patients with otherwise unexplained GI symptoms. Importantly, whether eradication or its treatment leads to resolution of symptoms remains unclear; at present, a 2-3-week course of antifungal therapy is recommended and may be effective in improving symptoms, but evidence for eradication is lacking.
Human intestinal microbiota create a complex polymicrobial ecology. This is characterised by its high population density, wide diversity and complexity of interaction. Any dysbalance of this complex intestinal microbiome, both qualitative and quantitative, might have serious health consequence for a macro-organism, including small intestinal bacterial overgrowth syndrome (SIBO). SIBO is defined as an increase in the number and/or alteration in the type of bacteria in the upper gastrointestinal tract. There are several endogenous defence mechanisms for preventing bacterial overgrowth: gastric acid secretion, intestinal motility, intact ileo-caecal valve, immunoglobulins within intestinal secretion and bacteriostatic properties of pancreatic and biliary secretion. Aetiology of SIBO is usually complex, associated with disorders of protective antibacterial mechanisms (e.g. achlorhydria, pancreatic exocrine insufficiency, immunodeficiency syndromes), anatomical abnormalities (e.g. small intestinal obstruction, diverticula, fistulae, surgical blind loop, previous ileo-caecal resections) and/or motility disorders (e.g. scleroderma, autonomic neuropathy in diabetes mellitus, post-radiation enteropathy, small intestinal pseudo-obstruction). In some patients more than one factor may be involved. Symptoms related to SIBO are bloating, diarrhoea, malabsorption, weight loss and malnutrition. The gold standard for diagnosing SIBO is still microbial investigation of jejunal aspirates. Non-invasive hydrogen and methane breath tests are most commonly used for the diagnosis of SIBO using glucose or lactulose. Therapy for SIBO must be complex, addressing all causes, symptoms and complications, and fully individualised. It should include treatment of the underlying disease, nutritional support and cyclical gastro-intestinal selective antibiotics. Prognosis is usually serious, determined mostly by the underlying disease that led to SIBO.
Background
The diagnosis of small intestinal bacterial overgrowth (SIBO) remains challenging. Our aim was to examine the diagnostic yield of duodenal aspiration/culture and glucose breath test (GBT), and effects of gender, race and demographics on prevalence of SIBO.Methods
Patients with unexplained gas, bloating and diarrhea and negative endoscopy, imaging and blood tests were prospectively enrolled in two centers in USA. Randomly, within 1 week each patient underwent both duodenal aspiration/culture and GBT. The diagnostic yield of each test and relationship of symptoms, and effects of ethnicity, age, and gender on prevalence of SIBO were assessed and compared.Key ResultsDuodenal culture was positive in 62/139 (44.6%) subjects and GBT was positive in 38/139 (27.3%) subjects with an overall diagnostic agreement of 65.5%. The sensitivity, specificity, positive and negative predictive value of GBT was 42%, 84%, 68%, and 64%, respectively. Ethnicity or gender did not influence SIBO, but SIBO positive patients were older (p = 0.0018). Symptom patterns were similar except bloating was more prevalent in GBT positive and gas in culture positive subjects.Conclusions & InferencesDuodenal aspiration/culture identifies 45% of patients with suspected SIBO. GBT has lower sensitivity but good specificity for detection of SIBO. There were no ethnic or gender differences in the prevalence of SIBO, but patients with SIBO were older. Because GBT is non-invasive, it should be considered first in patients with suspected SIBO.
Goals:
To assess the prevalence of small intestinal bacterial overgrowth (SIBO) in chronic pancreatitis (CP), and analyze factors related with SIBO in CP.
Background:
SIBO is to be considered a factor that worsens symptoms and nutritional status in patients with CP. However, the few studies evaluating the rate of SIBO in CP patients used nonuniform and nonstandardized procedures, and reported a wide range of positivity (0% to 92%). Those studies often investigated CP patients with previous resection surgery (cause of SIBO per se).
Study:
CP patients and controls evaluated for SIBO by the H2 glucose breath test with a standard protocol. For CP patients, the relationship between test results, abdominal symptoms, and clinical and biochemical variables was analyzed.
Results:
A total of 43 CP patients and 43 controls were enrolled. Of the CP patients, 8 had advanced disease (defined by M-ANNHEIM index) and none had undergone previous surgery. The glucose breath test positivity rate was higher in the CP patients than in the controls (21% vs. 14%), albeit without a significant difference (P=0.57). Mean fasting H2 excretion and mean H2 excretion at 120 minutes also had a trend toward higher levels in CP patients. There were no clinical differences between CP patients with or without SIBO, but there were nutritional differences for lower levels of vitamin D and higher levels of folate in these patients with SIBO.
Conclusions:
Our findings suggest that SIBO is not uncommon in uncomplicated CP patients. The lack of a significant difference compared with controls might be due to the study being underpowered. SIBO in CP patients does not seem to be related to peculiar clinical features, but it might affect nutritional status.
Objective:
Patients with small intestine bacterial overgrowth (SIBO) have chronic intestinal and extraintestinal symptomatology which adversely affects their quality of life. Present treatment of SIBO is limited to oral antibiotics with variable success. A growing number of patients are interested in using complementary and alternative therapies for their gastrointestinal health. The objective was to determine the remission rate of SIBO using either the antibiotic rifaximin or herbals in a tertiary care referral gastroenterology practice.
Design:
One hundred and four patients who tested positive for newly diagnosed SIBO by lactulose breath testing (LBT) were offered either rifaximin 1200 mg daily vs herbal therapy for 4 weeks with repeat LBT post-treatment.
Results:
Three hundred ninety-six patients underwent LBT for suspected SIBO, of which 251 (63.4%) were positive 165 underwent treatment and 104 had a follow-up LBT. Of the 37 patients who received herbal therapy, 17 (46%) had a negative follow-up LBT compared to 23/67 (34%) of rifaximin users (P=.24). The odds ratio of having a negative LBT after taking herbal therapy as compared to rifaximin was 1.85 (CI=0.77-4.41, P=.17) once adjusted for age, gender, SIBO risk factors and IBS status. Fourteen of the 44 (31.8%) rifaximin non-responders were offered herbal rescue therapy, with 8 of the 14 (57.1%) having a negative LBT after completing the rescue herbal therapy, while 10 non-responders were offered triple antibiotics with 6 responding (60%, P=.89). Adverse effects were reported among the rifaximin treated arm including 1 case of anaphylaxis, 2 cases of hives, 2 cases of diarrhea and 1 case of Clostridium difficile. Only one case of diarrhea was reported in the herbal therapy arm, which did not reach statistical significance (P=.22).
Conclusion:
SIBO is widely prevalent in a tertiary referral gastroenterology practice. Herbal therapies are at least as effective as rifaximin for resolution of SIBO by LBT. Herbals also appear to be as effective as triple antibiotic therapy for SIBO rescue therapy for rifaximin non-responders. Further, prospective studies are needed to validate these findings and explore additional alternative therapies in patients with refractory SIBO.
The antibiotic rifaximin is used to treat non-constipated irritable bowel syndrome (IBS). Methane production is associated with constipation and its severity in constipation-predominant IBS (C-IBS). A previous retrospective study suggested that rifaximin and neomycin was superior to neomycin alone in improving symptoms in methane-positive subjects.
To determine the effectiveness of neomycin alone or with rifaximin in improving symptoms in methane-positive C-IBS subjects.
A double-blind, randomized, placebo-controlled trial was performed from 2010 to 2013 at three tertiary care centers. Subjects aged 18-65 with C-IBS (Rome II criteria) and breath methane (>3 ppm) meeting the inclusion and exclusion criteria were recruited. Subjects completed a baseline symptom questionnaire rating the severity of abdominal and bowel symptoms on a visual analog scale and were randomized to receive neomycin and placebo or neomycin and rifaximin for 14 days. Symptom severity was assessed by weekly questionnaire for 2 weeks of therapy and 4 additional weeks of follow-up.
Thirty-one subjects (16 neomycin and placebo, 15 neomycin and rifaximin) were included in the intention-to-treat analysis. Constipation severity was significantly lower in the neomycin and rifaximin group (28.6 ± 30.8) compared to neomycin alone (61.2 ± 24.1) (P = 0.0042), with greater improvement in constipation (P = 0.007), straining (P = 0.017) and bloating (P = 0.020), but not abdominal pain. In the neomycin and rifaximin group, subjects with methane <3 ppm after treatment reported significantly lower constipation severity (30.5 ± 21.8) than subjects with persistent methane (67.2 ± 32.1) (P = 0.020).
Rifaximin plus neomycin is superior to neomycin alone in improving multiple C-IBS symptoms. This effect is predicted by a reduction in breath methane.
Candida is a yeast species recognized as the most frequent etiological agent of systemic and invasive thrush in humans. Invasions can affect all tissues, organs and systems of human in various stages of development. In the last 10 years Candida infections have increased 15 times. The purpose of our study was to determine the sensitivity of four antibiotics belonging to three different groups of antifungal agents against clinical and food-borne Candida strains. Our studies showed that of all tested strains, 7% was resistant to nystatin, 32% to fluconazole, 23% to voriconazole, and no strains grew in the presence of caspofungin. Despite the differences in biochemical profiles of clinical and food-borne isolates of Candida, a group of strains showing resistance to antibiotics include both types of isolates. At the same time circulating of antibiotic-resistant strains outside the hospital environment and the yeast infection via food is possible.
Small intestinal bacterial overgrowth (SIBO) is an under-recognised diagnosis with important clinical implications when untreated. However, the optimal treatment regimen remains unclear.
To perform a systematic review and meta-analysis comparing the clinical effectiveness of antibiotic therapies in the treatment of symptomatic patients with documented SIBO.
Four databases were searched to identify clinical trials comparing effectiveness of: (i) different antibiotics, (ii) different doses of the same antibiotic and (iii) antibiotics compared with placebo. Data were independently extracted according to predetermined inclusion and exclusion criteria. Study quality was independently assessed. The primary outcome was normalisation of post-treatment breath testing. The secondary outcome was post-treatment clinical response.
Of 1356 articles identified, 10 met inclusion criteria. Rifaximin was the most commonly studied antibiotic (eight studies) with overall breath test normalisation rate of 49.5% (95% confidence interval, CI 44.0-55.1) (44.0%-55.1%) then (46.7%-55.5%), then (4.6%-17.8%). Antibiotic efficacy varied by antibiotic regimen and dose. Antibiotics were more effective than placebo, with a combined breath test normalisation rate of 51.1% (95% CI 46.7-55.5) for antibiotics compared with 9.8% (95% CI 4.6-17.8) for placebo. Meta-analysis of four studies favoured antibiotics over placebo for breath test normalisation with an odds ratio of 2.55 (95% CI 1.29-5.04). Clinical response was heterogeneously evaluated among six studies, but tended to correlate with breath test normalisation.
Antibiotics appear to be more effective than placebo for breath test normalisation in patients with symptoms attributable to SIBO, and breath test normalisation may correlate with clinical response. Studies were limited by modest quality, small sample size and heterogeneous design. Additional higher quality clinical trials of SIBO therapy are warranted.
Small intestinal bacterial overgrowth (SIBO) is defined as the presence of an abnormally high number of coliform bacteria in the small bowel. It is associated with a broad range of predisposing small intestinal motility disorders and with surgical procedures that result in bowel stasis. The most common symptoms associated with SIBO include diarrhea, flatulence, abdominal pain and bloating. Quantitative culture of small bowel contents and a variety of indirect tests have been used over the years in an attempt to facilitate the diagnosis of SIBO. The indirect tests include breath tests and biochemical tests based on bacterial metabolism of a variety of substrates. Unfortunately, there is no single valid test for SIBO, and the accuracy of all current tests remains limited due to the failure of culture to be a gold standard and the lack of standardization of the normal bowel flora in the small intestine. Currently, the ideal approach to treat SIBO is to treat the underlying disease, eradicate overgrowth, and address nutritional deficiencies that may be associated with the development of SIBO.
The symptoms and signs of small intestinal bacterial overgrowth (SIBO) are often identical to a variety of diseases and can lead to diagnostic confusion.
To review the diagnostic options for SIBO and present new investigative options for the condition.
A literature search was performed on MEDLINE, EMBASE and Web of Science for English articles and abstracts. Search terms included free text words and combinations of the following terms 'small intestinal bacterial overgrowth', 'small bowel bacterial overgrowth', 'diagnostic tests', 'treatment', 'antibiotics', 'probiotics', 'metabonomics', 'proton nuclear magnetic resonance spectroscopy', 'electronic nose' and 'field asymmetric ion mobility spectrometry'.
All of the available methods to test for SIBO have inherent limitations and no 'gold-standard' diagnostic test for the condition exists. Accurate diagnosis of SIBO requires identification of bacterial species growing inappropriately within the small intestine and symptom response to antibiotics. Proton nuclear magnetic resonance spectroscopy, electronic nose technology and/or field asymmetric ion mobility spectrometry may represent better investigative options for the condition.
Novel diagnostic options are needed to supplement or replace available tests.