Review Article
Altered molecular signature of intestinal microbiota in irritable bowel syndrome patients compared with healthy controls: A systematic review and meta-analysis

https://doi.org/10.1016/j.dld.2017.01.142Get rights and content

Abstract

Background

Many studies have reported significant changes in intestinal microbiota in irritable bowel syndrome (IBS) patients based on quantitative real-time PCR analysis.

Aims

We aimed to review the alterations in intestinal microbiota.

Methods

An online search up to June 9, 2016, was conducted. This systematic review and meta-analysis included differential expression of intestinal microbiota in patients with IBS versus healthy controls (HCs) and subgroup analysis. We assessed the quality of the included studies using an original assessment tool.

Results

A total of 13 articles involving 360 IBS patients and 268 healthy controls were included. The quality assessment scores for these articles ranged from 5 to 8. Significant differences in expression in IBS patients were observed for Lactobacillus (SMD = −0.85, P < 0.001, I2 = 28%), Bifidobacterium (SMD = −1.17, P < 0.001, I2 = 79.3%), and Faecalibacterium prausnitzii (SMD = −1.05, P < 0.001, I2 = 0.0%) but not Bacteroides-Prevotella group, Escherichia coli or other genera or species. Subgroup analysis showed that diarrhea-predominant IBS patients had significantly different expression of Lactobacillus (SMD = −1.81, P < 0.001) and Bifidobacterium (SMD = −1.45, P < 0.001).

Conclusion

Down-regulation of bacterial colonization including Lactobacillus, Bifidobacterium and F. prausnitzii was observed in IBS patients, particularly in diarrhea-predominant IBS (IBS-D). Microbiota changes participate in the pathogenesis of IBS and may underlie the efficacy of probiotic supplements.

Introduction

Irritable Bowel Syndrome (IBS), which affects 10–20% of adults and adolescents [1], is a common functional disorder of the gastrointestinal tract. The characteristics of IBS are abdominal pain or discomfort, distorted bowel habits and altered stool characteristics. Due to the differing symptoms experienced, patients diagnosed with IBS are divided into three groups: diarrhea-predominant (IBS-D), constipation-predominant (IBS-C) and mixed-type (IBS-M). The etiology and pathogenesis of IBS remain unclear, and roles for central neural dysfunction, psychological disturbances, stress, and luminal factors have been proposed [2]. In addition, increasing evidence supports an important role of the intestinal microbiota in the pathophysiology of IBS. These roles include differences in microbiota compared with healthy populations, the observation of small intestinal bacterial overgrowth (SIBO), the development of IBS after intestinal infection, and the efficacy of probiotics in IBS treatment [3], [4].

The intestinal microbiota is a complicated system. To investigate microbial community structure, research techniques have expanded from traditional culture-based methods to molecular techniques, including fluorescence in situ hybridization (FISH), DNA microarrays, denaturing gradient gel electrophoresis (DGGE), real-time quantitative PCR, and even the latest pyrosequencing methods [5]. Compared with previous qualitative or semi-quantitative methods, real-time quantitative PCR, which was invented in 1996, is a revolutionary molecular technique with clear advantages, such as accurate quantification, high sensitivity, specificity and reproducibility. Compared with the newest pyrosequencing methods, q-PCR is inexpensive and has been used to validate pyrosequencing screening.

Decades of study of the abundant changes in various bacteria in IBS patients using diverse techniques have yielded different and even conflicting results due to methodological limitations or other factors. Based on the advantages of q-PCR, we retrieved studies using q-PCR, performed a systematic review and meta-analysis of the differential expression of the intestinal microbiota in IBS, and discuss the potential implications.

Section snippets

Search strategy

We retrieved reports from PubMed, Web of Science and Chinese Biomedical Literature Database (CBM) up to June 9, 2016. The search strategy was "(IBS OR “irritable bowel syndrome”) AND (q-PCR OR q-PCR OR real-time) AND (microbiome OR microbiota OR flora)". Lists of review article references and the original articles were searched manually for additional publications.

Inclusion criteria and exclusion criteria

For inclusion in this systematic review, the following criteria had to be met: (1) intestinal microbiota studies comparing IBS

Study selection and characteristics

Literature searches of the databases yielded 151 studies, of which 37 were from PubMed, 92 were from Web of Science, and 22 were from CBM. After removing duplicates, 118 were retained. Finally, 13 articles met our inclusion criteria after removing animal studies, intervention studies, letters and reviews (Fig. 1) [8], [9], [10], [11], [12], [13], [14], [21], [22], [23], [24], [25], [26]. A total of 360 IBS patients and 268 healthy controls were included, with sample sizes ranging from 6 to 77.

Discussion

In this study, we choose q-PCR as the single method in the inclusion criteria to avoid clinical heterogeneity. Culture-based methods are considered inappropriate for the analysis of complex microbial ecosystems that are mainly composed of anaerobic bacteria [27]. FISH, DNA microarrays and DGGE are semi-quantitative methods with low precision [22], [28], [29]. In recent years, pyrosequencing has become an inexpensive, routine and widespread method for sequencing [30]. However, whole-genome

Conflict of interest

None declared.

Funding

This study was supported by the National Nature Science Foundation of China (No. 81000968; No. 81101540; No. 81101637; No. 81172273; No. 81272388; No. 81301820; No. 81472673), Doctoral Fund of Ministry of Education of China (20120071110058), and the National Key Clinical Specialty of China.

Financial disclosure

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Acknowledgments

The authors would like to thank the members of Prof. Xi-Zhong Shen’s laboratory for helpful discussions and critical reading of the manuscript and our colleague, Diana Yu Tseng, for revising grammatical errors.

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