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Reduction of butyrate- and methane-producing microorganisms in patients with Irritable Bowel Syndrome.

ABSTRACT: The pathophysiology of irritable bowel syndrome (IBS) remains unclear. Here we investigated the microbiome of a large cohort of patients to identify specific signatures for IBS subtypes. We examined the microbiome of 113 patients with IBS and 66 healthy controls. A subset of these participants provided two samples one month apart. We analyzed a total of 273 fecal samples, generating more than 20 million 16S rRNA sequences. In patients with IBS, a significantly lower microbial diversity was associated with a lower relative abundance of butyrate-producing bacteria (P = 0.002; q < 0.06), in particular in patients with IBS-D and IBS-M. IBS patients who did not receive any treatment harboured a lower abundance of Methanobacteria compared to healthy controls (P = 0.005; q = 0.05). Furthermore, significant correlations were observed between several bacterial taxa and sensation of flatulence and abdominal pain (P < 0.05). Altogether, our findings showed that IBS-M and IBS-D patients are characterized by a reduction of butyrate producing bacteria, known to improve intestinal barrier function, and a reduction of methane producing microorganisms a major mechanism of hydrogen disposal in the human colon, which could explain excess of abdominal gas in IBS.

SUBMITTER: Pozuelo M

PROVIDER: S-EPMC4523847 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Reduction of butyrate- and methane-producing microorganisms in patients with Irritable Bowel Syndrome.

Pozuelo Marta M Panda Suchita S Santiago Alba A Mendez Sara S Accarino Anna A Santos Javier J Guarner Francisco F Azpiroz Fernando F Manichanh Chaysavanh C

Scientific reports 20150804

The pathophysiology of irritable bowel syndrome (IBS) remains unclear. Here we investigated the microbiome of a large cohort of patients to identify specific signatures for IBS subtypes. We examined the microbiome of 113 patients with IBS and 66 healthy controls. A subset of these participants provided two samples one month apart. We analyzed a total of 273 fecal samples, generating more than 20 million 16S rRNA sequences. In patients with IBS, a significantly lower microbial diversity was assoc ...[more]

PMID: 26239401

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Project description:BackgroundThe intestinal microbiota is thought to be involved in the occurrence of inflammatory bowel disease in remission with irritable bowel syndrome (IBS)-type symptoms, but the specific distinct profile of these bacteria remains unclear. This cross-sectional study aims to investigate the fecal microbiota profiling in patients with these diseases.MethodsFecal samples from 97 subjects, including Crohn's disease patients in remission with IBS-type symptoms (CDR-IBS+) or without IBS-type symptoms (CDR-IBS-), ulcerative colitis patients in remission with IBS-type symptoms (UCR-IBS+) or without IBS-type symptoms (UCR-IBS-), IBS patients and healthy controls, were collected and applied 16S ribosomal DNA (rDNA) gene sequencing. The V4 hypervariable regions of 16S rDNA gene were amplified and sequenced by the Illumina MiSeq platform. The differences in the sample diversity index in groups were analyzed with R software.ResultsThe richness of the intestinal microbiota in the CDR-IBS group was markedly lower than those in the control and IBS groups based on the analysis of observed species and the Chao index (P < 0.05). The observed species index in the CDR-IBS+ group was higher than that in the CDR-IBS- group (median index: 254.8 vs 203, P = 0.036). No difference was found in alpha diversity between UCR patients with IBS-type symptoms and those without related symptoms. At the genus level, the number of Faecalibacterium in CDR patients with IBS-type symptoms increased significantly, while Fusobacterium decreased versus those without such symptoms (mean relative abundance of Faecalibacterium: 20.35% vs 5.18%, P < 0.05; Fusobacterium: 1.51% vs 5.2%, P < 0.05). However, compared with the UCR-IBS- group, the number of Faecalibacterium in the UCR-IBS+ group decreased, while the number of Streptococcus increased, but there was no significant difference in the genus structure. The abundance and composition of the microbiota of IBS patients were not distinct from those of healthy controls.ConclusionsThe IBS-type symptoms in CD patients in remission may be related to an increase in Faecalibacterium and a decrease in Fusobacterium. The IBS-type symptoms in UC patients in remission cannot be explained by changes in the abundance and structure of the intestinal microbiota.

Project description:BackgroundPrevious studies have indicated that ramosetron, a 5-hydroxytryptamine-3 receptor antagonist, achieves global improvement in irritable bowel syndrome (IBS) symptoms in male patients with IBS with diarrhea (IBS-D). However, in addition to global assessment it was deemed important to assess "clinically meaningful improvements, focusing on the patient's chief complaint and the severity of major IBS symptoms". We performed a randomized, placebo-controlled, phase IV pilot study to explore and examine efficacy variables that allow such evaluation of ramosetron in male patients with IBS-D.MethodsWe performed a prospective study of 115 male outpatients with IBS-D (according to the Rome III criteria), from June 2009 to December 2009 at 25 centers in Japan. After a one-week baseline period, subjects received either 5 μg of ramosetron (n = 47) or placebo (n = 51) once daily for 12 weeks. To evaluate "clinically meaningful improvements focusing on the severity of major IBS symptoms," the Japanese version of the IBS severity index (IBSSI-J) was used.ResultsChange in IBSSI-J overall score from baseline was -133.5 ± 110.72 in the ramosetron 5 μg group and -108.2 ± 94.44 in the placebo group (P = 0.228) at the last evaluation point. Differences in responder rates for at least a 50% reduction from baseline in IBSSI-J between the ramosetron 5 μg group and the placebo group were over 10%, except Month 1. The monthly responder rate for global assessment of relief of overall IBS symptoms in the ramosetron 5 μg group showed a statistically significant improvement compared to placebo at the second month (44.4% vs 18.4%, P = 0.012). The proportion of patients who had a ≥ 50% reduction in IBSSI-J overall score was 24/37 (64.9%) in the responder group on global assessment and 18/54 (33.3%) in the non-responder group at Week 12.ConclusionsFurther examination will be needed before IBSSI-J can be used in clinical trials of agents for IBS-D. However, this study revealed that response on global assessment was correlated with improvement in the IBSSI-J, suggesting that global assessment reflects improvement of the symptom severity of patients with IBS-D. (Clinicaltrials.gov ID: NCT00918411 Registered 9 June 2009).

Project description:BackgroundDiarrhea-predominant irritable bowel syndrome (IBS-d) significantly diminishes the health-related quality of life (HRQOL) of patients. Psychological and social impacts are common with many IBS-d patients reporting comorbid depression, anxiety, decreased intimacy, and lost working days. The Irritable Bowel Syndrome Quality of Life (IBS-QOL) questionnaire is a 34-item instrument developed and validated for measurement of HRQOL in non-subtyped IBS patients. The current paper assesses this previously-validated instrument employing data collected from 754 patients who participated in a randomized clinical trial of a novel treatment, eluxadoline, for IBS-d.MethodsPsychometric methods common to HRQOL research were employed to evaluate the IBS-QOL. Many of the historical analyses of the IBS-QOL validations were used. Other techniques that extended the original methods were applied where more appropriate for the current dataset. In IBS-d patients, we analyzed the items and substructure of the IBS-QOL via item reduction, factor structure, internal consistency, reproducibility, construct validity, and ability to detect change.ResultsThis study supports the IBS-QOL as a psychometrically valid measure. Factor analyses suggested that IBS-specific QOL as measured by the IBS-QOL is a unidimensional construct. Construct validity was further buttressed by significant correlations between IBS-QOL total scores and related measures of IBS-d severity including the historically-relevant Irritable Bowel Syndrome Adequate Relief (IBS-AR) item and the FDA's Clinical Responder definition. The IBS-QOL also showed a significant ability to detect change as evidenced by analysis of treatment effects. A minority of the items, unrelated to the IBS-d, performed less well by the standards set by the original authors.ConclusionsWe established that the IBS-QOL total score is a psychometrically valid measure of HRQOL in IBS-d patients enrolled in this study. Our analyses suggest that the IBS-QOL items demonstrate very good construct validity and ability to detect changes due to treatment effects. Furthermore, our analyses suggest that the IBS-QOL items measure a univariate construct and we believe further modeling of the IBS-QOL from an item response theory (IRT) approach under both non-treatment and treatment conditions would greatly further our understanding as item-based methods could be used to develop a short form.

Dataset Information

Reduction of butyrate- and methane-producing microorganisms in patients with Irritable Bowel Syndrome.

Publications

Reduction of butyrate- and methane-producing microorganisms in patients with Irritable Bowel Syndrome.

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