Gastroenterology

Gastroenterology

Volume 141, Issue 5, November 2011, Pages 1792-1801
Gastroenterology

Original Research
Basic and Translational—Alimentary Tract
Global and Deep Molecular Analysis of Microbiota Signatures in Fecal Samples From Patients With Irritable Bowel Syndrome

https://doi.org/10.1053/j.gastro.2011.07.043Get rights and content

Background & Aims

Irritable bowel syndrome (IBS) has been associated with disruptions to the intestinal microbiota, but studies have had limited power, coverage, and depth of analysis. We aimed to define microbial populations that can be used discriminate the fecal microbiota of patients with IBS from that of healthy subjects and correlate these with IBS intestinal symptom scores.

Methods

The microbiota composition was assessed by global and deep molecular analysis of fecal samples from 62 patients with IBS patients and 46 healthy individuals (controls). We used a comprehensive and highly reproducible phylogenetic microarray in combination with quantitative polymerase chain reaction.

Results

The intestinal microbiota of IBS patients differed significantly (P = .0005) from that of controls. The microbiota of patients, compared with controls, had a 2-fold increased ratio of the Firmicutes to Bacteroidetes (P = .0002). This resulted from an approximately 1.5-fold increase in numbers of Dorea, Ruminococcus, and Clostridium spp (P < .005); a 2-fold decrease in the number of Bacteroidetes (P < .0001); a 1.5-fold decrease in numbers of Bifidobacterium and Faecalibacterium spp (P < .05); and, when present, a 4-fold lower average number of methanogens (3.50 × 107 vs 8.74 × 106 cells/g feces; P = .003). Correlation analysis of the microbial groups and IBS symptom scores indicated the involvement of several groups of Firmicutes and Proteobacteria in the pathogenesis of IBS.

Conclusions

Global and deep molecular analysis of fecal samples indicates that patients with IBS have a different composition of microbiota. This information might be used to develop better diagnostics and ultimately treatments for IBS.

Section snippets

Participants

The study group consisted of 62 primary care IBS patients and 46 healthy subjects, all recruited from the Helsinki area in Finland for 2 follow-up clinical trials that recruited IBS patients17 and healthy subjects.18 IBS patients fulfilled the Rome II criteria,19 were recruited in primary health care centers, and had a clinical investigation with colonoscopy or barium enema of the colon performed during the preceding 5 years. The IBS patients were divided across 3 subgroups:

Phylogenetic Profiling and Multivariate Analysis of the Total Fecal Microbiota

The microarray datasets of the fecal microbiota derived from 62 IBS patients and 46 healthy subjects were acquired and hierarchically clustered based on the signal intensity of the 3699 distinct HITChip oligonucleotide probes (Figure 1). The IBS and healthy subjects did not cluster significantly according to their health status, testifying for the individuality of the microbiota when analyzed at the phylotype level. The microbiota profiles were compared by using the average hybridization signal

Discussion

The composition of the total fecal microbiota of the 62 IBS patients and 46 healthy controls was found to be strongly and significantly influenced by the health status of the subjects. A clear and consistent multivariate separation was obtained with all of the more than 100 analyzed fecal samples into an IBS or healthy group (Figure 2). This extends similar observations made with pooled fecal DNA samples of about 50 subjects11 because the present study shows the global microbiota analysis of

Conclusions

We have presented the results of a comprehensive analysis using high throughput DNA technologies that showed specific and robust signatures in the fecal microbiota of IBS patients, some of which were characteristic for the studied IBS subtypes. These signatures provide a molecular basis for designing specific detection approaches. Despite the fact that the fecal microbiota is an extremely complex ecosystem varying significantly among individuals, most of the deviations reported here accommodate

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    Conflicts of interest The authors disclose no conflicts.

    Funding This work was partially funded by the unrestricted Spinoza Award of the Netherlands Organization of Scientific Research awarded to WMdV.

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