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Hydrogen sulfide small intestinal bacterial overgrowth case registry
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Abstract
Background: There is growing interest in hydrogen sulfide small intestinal bacterial overgrowth (H2S SIBO). However, basic questions including how clinicians are making the diagnosis, what symptoms are present, and what clinicians are using for treatment, remain unanswered.
Aims: To address this, we created an online, survey-based, clinical registry of H2S SIBO cases.
Methods: Participants in this study were clinicians diagnosing and treating patients with H2S SIBO and input data on patient presentation, diagnosis, treatment, and treatment response. We describe the population and summarize our results using descriptive statistics. We use Pearson's chi-squared test and modified Poisson regression in exploratory analyses.
Results: 131 total cases were submitted by 99 providers across a spectrum of health disciplines. The mean patient age was 45.6 (71.4% female). The most common symptoms were bloating (77.0%), constipation (50.8%) and abdominal pain (50.8%). Diagnosis was made based on flatline hydrogen in the 3rd hour of a lactulose breath test (42.5%), symptom presentation (empiric) (31.9%), or H2S levels (25.7%). The most common treatments used were a low sulfur diet (46.6%), oregano (44.0%), and bismuth (39.7%). Fifty-eight percent of cases were responders. Of the most common interventions used, only a low sulfur diet (73% responder; p=0.01) and bismuth (76% responder; p=0.01) were significantly associated with treatment response. Interestingly, response rates differed based on how H2S SIBO was diagnosed, with empiric underperforming flatline diagnoses (relative risk 0.60; p=0.04).
Conclusions: This case registry represents the largest collection of H2S SIBO cases to-date, providing important early descriptive information on this emerging diagnosis.
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Objectives:
Irritable bowel syndrome (IBS) includes diarrhea-predominant (IBS-D) and constipation-predominant (IBS-C) subtypes. We combined breath testing and stool microbiome sequencing to identify potential microbial drivers of IBS subtypes.
Methods:
IBS-C and IBS-D subjects from two randomized controlled trials (NCT03763175, NCT04557215) were included. Baseline breath carbon dioxide, hydrogen (H2), methane (CH4), and hydrogen sulfide (H2S) levels were measured by gas chromatography, and baseline stool microbiome composition was analyzed by 16S rRNA sequencing. Microbial metabolic pathways were analyzed using Kyoto Encyclopedia of genes and Genomes (KEGG) collection databases.
Results:
IBS-C subjects had higher breath CH4 that correlated with higher gut microbial diversity and higher relative abundance (RA) of stool methanogens, predominantly Methanobrevibacter, as well as higher absolute abundance of Methanobrevibacter smithii in stool. IBS-D subjects had higher breath H2 which correlated with lower microbial diversity, and higher breath H2S which correlated with higher RA of H2S-producing bacteria, including Fusobacterium and Desulfovibrio spp. The predominant H2 producers were different in these distinct microtypes, with higher RA of Ruminococcaceae and Christensenellaceae in IBS-C/CH4+ (which correlated with Methanobacteriaceae RA), and higher Enterobacteriaceae RA in IBS-D. Lastly, microbial metabolic pathway analysis revealed enrichment of KEGG modules associated with methanogenesis and biosynthesis of methanogenesis co-factor F420 in IBS-C/CH4+ subjects, whereas modules associated with H2S production, including sulfate reduction pathways, were enriched in IBS-D.
Conclusions:
Our findings identify distinct gut microtypes linked to breath gas patterns in IBS-C and IBS-D subjects, driven by methanogens such as M. smithii and H2S producers such as Fusobacterium and Desulfovibrio spp, respectively.
The small-large intestine axis in hydrogen sulfide accumulation and testing of sulfate and lactate in the gut-gut axis of the intestinal environment has not been well described. Sulfate reducing bacteria (SRB) of the Desulfovibrio genus reduce sulfate to hydrogen sulfide and can be involved in ulcerative colitis development. The background of the research was to find correlations between hydrogen sulfide production under the effect of an electron acceptor (sulfate) and donor (lactate) at different concentrations and Desulfovibrio piger Vib-7 growth, as well as their dissimilatory sulfate reduction in the intestinal small-large intestinal environment.
Methods:
Microbiological, biochemical, and biophysical methods, and statistical processing of the results (principal component and cross-correlation analyses) were used.
Results:
D. piger Vib-7 showed increased intensity of bacterial growth and hydrogen sulfide production under the following concentrations of sulfate and lactate: 17.4 mM and 35.6 mM, respectively. The study showed in what kind of intestinal environment D. piger Vib-7 grows at the highest level and produces the highest amount of hydrogen sulfide.
Conclusions:
The optimum intestinal environment of D. piger Vib-7 can serve as a good indicator of the occurrence of inflammatory bowel diseases; meaning that these findings can be broadly used in medicine practice dealing with the monitoring and diagnosis of intestinal ailments.
Background and Aim
Breath testing has become a commonly used tool in gastroenterology to evaluate changes in the fermentation pattern of the gut microbiome. Currently, hydrogen and methane gas concentrations are measured in breath testing and evaluated against specific cut‐off values for interpretation as normal or abnormal. However, microbial gas kinetics is a complex process that is not currently fully considered when interpreting breath gas results. Gas exchange between hydrogen producers and hydrogen consumers (methanogens and sulfate‐reducing bacteria) is a process whereby hydrogen availability is determined by both its production and removal. Hydrogen sulfide is a crucial gas involved in this process as it is a major hydrogen‐consumptive pathway involved in energy exchange.
Methods
This is a cross‐sectional study evaluating lactulose breath testing with the inclusion of hydrogen sulfide measurements in patients referred for breath testing for gastrointestinal symptoms of bloating, excessive gas, and/or abdominal pain.
Results
A total of 159 patients were analyzed between October 2016 and June 2017. Mean hydrogen concentrations with a positive trend through a 3‐h period (R² = 0.97), mean methane concentrations with a positive trend (R² = 0.69), and mean hydrogen sulfide concentrations with a negative trend (R² = −0.71) were observed.
Conclusion
By incorporating energy exchange in the interpretation of the lactulose breath test, we reevaluated specific breath gas profiles, including those commonly described as “hydrogen nonproducers” and the “double‐peak” phenomenon.
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:
Small intestinal bacterial overgrowth (SIBO) is a heterogeneous syndrome, characterised by an increased number and/or abnormal type of bacteria in the small bowel. Over the past decades, rifaximin has gained popularity for this indication despite its use is not evidence based.
Aim:
To perform a systematic review and meta-analysis to summarise evidence about the efficacy and safety of rifaximin to eradicate SIBO in adult patients.
Methods:
MEDLINE, EMBASE, CCRCT, Scopus and Web of Science were searched from inception to March 16, 2015 for RCTs and observational studies. Furthermore, abstract books of major European, American and Asian gastroenterological meetings were also examined.
Results:
Thirty-two studies involving 1331 patients were included. The overall eradication rate according to intention-to-treat analysis was 70.8% (95% CI: 61.4-78.2; I(2) = 89.4%) and to per protocol analysis 72.9% (95% CI: 65.5-79.8; I(2) = 87.5%). Meta-regression identified three covariates (drug dose, study design and co-therapy) independently associated with an increased eradication rate. The overall rate of adverse events was 4.6% (95% CI: 2.3-7.5; I(2) = 63.6%). In the subset of studies (n= 10) allowing the analysis, improvement or resolution of symptoms in patients with eradicated SIBO was found to be 67.7% (95% CI: 44.7-86.9; I(2) = 91.3%).
Conclusions:
Rifaximin treatment seems to be effective and safe for the treatment of SIBO. However, the quality of the available studies is generally poor. Well-designed RCTs are needed to substantiate these findings and to establish the optimal regimen.
For centuries plants have been used for a wide variety of purposes, from treating infectious diseases to food preservation and perfume production. Presently, the increasing resistance of microorganisms to currently used antimicrobials in combination with the appearance of emerging diseases requires urgently the development of new, more effective drugs. Plants, due to the large biological and structural diversity of their components, constitute a unique and renewable source for the discovery of new antibacterial, antifungal and antiparasitic treatments. In the present paper, the history, composition and antimicrobial activities of the Basil, Oregano and Thyme essential oils are reviewed.
Purpose:
Among irritable bowel syndrome (IBS) patients, breath methane producers overwhelmingly have constipation predominance (C-IBS). Although the most common methanogen in humans is Methanobrevibacter smithii, incidence and type of methanogenic bacteria in C-IBS patients are unknown.
Methods:
By use of a questionnaire and lactulose breath testing, subjects with Rome II C-IBS and methane (>3 ppm) were selected (n = 9). The control group included subjects with IBS who had no breath methane (n = 10). Presence of bacterial DNA was assessed in a stool sample of each subject by quantitative-PCR using universal 16S rDNA primer. M. smithii was quantified by use of a specific rpoB gene primer.
Results:
M. smithii was detected in both methane and non-methane subjects. However, counts and relative proportion of M. smithii were significantly higher for methane-positive than for methane-negative subjects (1.8 × 10(7) ± 3.0 × 10(7) vs 3.2 × 10(5) ± 7.6 × 10(5) copies/g wet stool, P < 0.001; and 7.1 ± 6.3 % vs 0.24 ± 0.47 %, P = 0.02 respectively). The minimum threshold of M. smithii resulting in positive lactulose breath testing for methane was 4.2 × 10(5) copies/g wet stool or 1.2 % of total stool bacteria. Finally, area-under-curve for breath methane correlated significantly with both absolute quantity and percentage of M. smithii in stool (R = 0.76; P < 0.001 and R = 0.77; P < 0.001 respectively).
Conclusions:
M. smithii is the predominant methanogen in C-IBS patients with methane on breath testing. The number and proportion of M. smithii in stool correlate well with amount of breath methane.
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.
Recent evidence suggests a role for enteric bacteria in the development of symptoms in subjects with irritable bowel syndrome (IBS). The concept was initially based on the common finding of an abnormal lactulose breath test to suggest the presence of small intestinal bacterial overgrowth (SIBO). Despite successful antibiotic studies based on these findings, the premise of bacterial overgrowth was met with skepticism due to the perceived inaccuracies of breath testing in humans. In this study, we conduct a systematic review and meta-analysis of the studies using breath testing in IBS subjects with comparison to healthy controls.
A literature search was conducted to identify studies in which breath testing was conducted in subjects with IBS. Once abstract titles were identified, studies that examined breath testing in a case-control fashion were identified for paper review. After exclusion criteria were applied, the remaining papers were examined using meta-analysis, among which the prevalence of an abnormal breath test in IBS subjects was compared. Further analysis was conducted among studies with appropriate age- and sex-matched controls.
Eleven studies met criteria for inclusion in the meta-analysis. Although heterogeneity was identified among studies on the basis of substrate used, lactulose was the most common substrate. In pooling the 11 studies, breath testing was more often abnormal among IBS subjects than health controls (OR=4.46, 95% CI=1.69-11.80). This was further evident in more appropriately designed age- and sex-matched studies (OR=9.64, 95% CI=4.26-21.82). The overall sensitivity and specificity for breath testing in separating IBS from healthy controls was 43.6 and 83.6%.
This study demonstrates that the breath test findings in IBS appear to be valid. While this meta-analysis does not suggest that the breath test findings imply SIBO, the abnormal fermentation timing and dynamics of the breath test findings support a role for abnormal intestinal bacterial distribution in IBS.
Hydrogen sulfide is one of the main malodorous compounds in human flatus. This toxic gas also has been implicated in the pathogenesis of ulcerative colitis. Therefore, a treatment that reduces colonic H2S levels could be clinically useful in the treatment of flatus odor and of ulcerative colitis. In this study the ability of bismuth subsalicylate, a compound that binds H2S, to reduce H2S release in the colon, was tested.
Homogenates made from human and rat feces were incubated with and without bismuth subsalicylate, and gas production was measured. Fecal samples from 10 healthy subjects were analyzed before and after ingestion of bismuth subsalicylate (524 mg four times a day) for 3-7 days.
Fecal homogenates showed a dose-dependent relationship between the concentration of bismuth subsalicylate and H2S release. Treatment of subjects with bismuth subsalicylate produced a >95% reduction in fecal H2S release.
The ability of bismuth subsalicylate to dramatically reduce H2S could provide a clinically useful means of controlling fecal and/or flatus odor and of decreasing the putative injurious effects of H2S on the colonic mucosa.