Global and Deep Molecular Analysis of Microbiota Signatures in Fecal Samples From Patients With Irritable Bowel Syndrome

Rajilić–Stojanović, Mirjana; Biagi, Elena; Heilig, Hans G.H.J.; Kajander, Kajsa; Kekkonen, Riina A.; Tims, Sebastian; de Vos, Willem M.

doi:10.1053/j.gastro.2011.07.043

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

Global and Deep Molecular Analysis of Microbiota Signatures in Fecal Samples From Patients With Irritable Bowel Syndrome

Mirjana Rajilić–Stojanović
- Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands
- Department of Biochemical Engineering and Biotechnology, Faculty of Technology and Metallurgy, University of Belgrade, Belgrade, Serbia
Elena Biagi
- Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands
Hans G.H.J. Heilig
- Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands
Kajsa Kajander
- Valio Ltd, R&D, Helsinki, Finland
Riina A. Kekkonen
- Valio Ltd, R&D, Helsinki, Finland
Sebastian Tims
- Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands
Willem M. de Vos
- Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands
- Departments of Veterinary Biosciences and Bacteriology and Immunology, University of Helsinki, Helsinki, Finland
- Reprint requests Address requests for reprints to: Willem M. de Vos, PhD, Laboratory of Microbiology, Wageningen University, Dreijenplein 10, 6703 HB Wageningen, The Netherlands. fax: +31317483829

Received 8 May 2011; accepted 27 July 2011. published online 08 August 2011.

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.

Keywords: High-Throughput Analysis , Phylogenetic Microarray , Microflora , Enterotypes

Abbreviations used in this paper: HITChip, human intestinal tract chip , IBS, irritable bowel syndrome , IBS-C, constipation-predominant IBS , IBS-D, diarrhea-predominant IBS , IBS-A, alternating-type IBS , qPCR, quantitative real-time polymerase chain reaction , rRNA, ribosomal RNA , SD, standard deviation