Review ArticleAltered molecular signature of intestinal microbiota in irritable bowel syndrome patients compared with healthy controls: A systematic review and meta-analysis
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.
References (41)
- et al.
Functional bowel disorders
Gastroenterology
(2006) - et al.
Gastrointestinal microbiome signatures of pediatric patients with irritable bowel syndrome
Gastroenterology
(2011) - et al.
Activation of human enteric neurons by supernatants of colonic biopsy specimens from patients with irritable bowel syndrome
Gastroenterology
(2009) - et al.
A serpin from the gut bacterium Bifidobacterium longum inhibits eukaryotic elastase-like serine proteases
The Journal of Biological Chemistry
(2006) - et al.
Harrison’s principles of internal medicine
(2004) Review article: evidence for the role of gut microbiota in irritable bowel syndrome and its potential influence on therapeutic targets
Alimentary Pharmacology and Therapeutics
(2014)- et al.
Irritable bowel syndrome and small intestinal bacterial overgrowth: meaningful association or unnecessary hype
World Journal of Gastroenterology
(2014) - et al.
Methodological issues in the study of intestinal microbiota in irritable bowel syndrome
World Journal of Gastroenterology
(2014) - et al.
The STARD statement for reporting studies of diagnostic accuracy: explanation and elaboration
Clinical Chemistry
(2003) - et al.
Differential expression of intestinal microbiota in colorectal cancer compared with healthy controls: a systematic review and meta-analysis
International Journal of Clinical and Experimental Medicine
(2016)
Changes of intestinal microflora in children with irritable bowel syndrome by SYBR Green I Real Time Fluo-rescent Quantitative PCR Method
Medical and Pharmaceutical Journal of Chinese People’s Liberation Army
Analysis of patients with intestinal target bacteria diarrhea type irritable bowel syndrome
Acta Universitatis Medicinalis Anhui
Increase in fecal primary bile acids and dysbiosis in patients with diarrhea-predominant irritable bowel syndrome
Neurogastroenterology and Motility
Altered profiles of intestinal microbiota and organic acids may be the origin of symptoms in irritable bowel syndrome
Neurogastroenterology and Motility
Analysis of the fecal microbiota of irritable bowel syndrome patients with 16S rDNA real-time PCR
Shandong Medical Journal
Analysis of the fecal microbiota of irritable bowel syndrome patients and healthy controls with real-time PCR
The American Journal of Gastroenterology
Development of an extensive set of 16S rDNA-targeted primers for quantification of pathogenic and indigenous bacteria in faecal samples by real-time PCR
Journal of Applied Microbiology
Detection of Lactobacillus, Pediococcus, Leuconostoc, and Weissella species in human feces by using group-specific PCR primers and denaturing gradient gel electrophoresis
Applied and Environmental Microbiology
Comparative assessment of human and farm animal faecal microbiota using real-time quantitative PCR
FEMS Microbiology Ecology
Development of 16S rRNA-gene-targeted group-specific primers for the detection and identification of predominant bacteria in human feces
Applied and Environmental Microbiology
Cited by (200)
The proteolytic activity in inflammatory bowel disease: insight from gut microbiota
2024, Microbial PathogenesisEffects of exposure to the neonicotinoid pesticide clothianidin on mouse intestinal microbiota under unpredictable environmental stress
2024, Toxicology and Applied PharmacologyRegulation of host immune responses by Lactobacillus through aryl hydrocarbon receptors
2023, Medicine in MicroecologyDietary fibre definition revisited - The case of low molecular weight carbohydrates
2023, Clinical Nutrition ESPENThe Role of the FODMAP Diet in IBS
2024, NutrientsHydrogen Sulfide Producers Drive a Diarrhea-Like Phenotype and a Methane Producer Drives a Constipation-Like Phenotype in Animal Models
2024, Digestive Diseases and Sciences