Could Differences in Gut Bacteria Cause IBS?
The bacteria that reside in the intestines of adults and children with irritable bowel syndrome (IBS) differ from those of healthy adults and children, according to 2 studies in the November issue of Gastroenterology.
Microorganisms account for 90% of the cells in our body (many cannot even be cultured); only 10% of our cells are human. The large microbial mass in the intestine is established at birth, and its composition is determined by a combination of genetic and environmental factors. The makeup of this microbiota has been proposed to affect development of inflammatory bowel diseases and IBS.
Only recently have researchers developed technologies to quantify these microbes. Mirjana Rajilić–Stojanović et al. performed global and deep molecular analysis of fecal samples from 62 adult patients with IBS and 46 healthy adults. In a separate study published in the same issue, Delphine M. Saulnier et al. analyzed 71 stool samples from 22 children with IBS and 22 healthy children using 16S ribosomal RNA gene sequencing.
Both studies found that patients with IBS had a greater abundance of the Firmicutes member Dorea than healthy individuals.
Rajilić–Stojanović et al. reported that adult patients with IBS had a 2-fold greater ratio of Firmicutes to Bacteroidetes than controls, resulting from an approximately 1.5-fold increase in numbers of Dorea, Ruminococcus, and Clostridium spp. They also observed a 2-fold decrease in the number of Bacteroidetes, a 1.5-fold decrease in numbers of Bifidobacterium and Faecalibacterium spp, and, when present, a 4-fold lower average number of methanogens (see figure).
The microbial groups correlated with IBS symptom scores, indicating that several groups of Firmicutes and Proteobacteria might mediate the development of IBS.
However, Saulnier et al. observed that the microbiomes of children with IBS had a significantly greater percentage of the class γ-proteobacteria. One prominent component of this group was Haemophilus parainfluenzae, but a novel, Ruminococcus-like microbe was also associated with IBS. Greater frequency of IBS pain in children correlated with an increased abundance of several bacterial taxa from the genus Alistipes. By contrast, taxa such as the genus Eubacterium and the species Bacteroides vulgatus were more frequently observed in healthy children.
Saulnier et al. were able to use their technology to identify children with IBS and determine their specific subtype, with greater than 95% accuracy. Different subtypes of IBS (IBS with constipation, IBS with diarrhea, etc.) were associated with different bacterial populations, encompassing at least 50–75 different taxa, so this technology might be used in diagnosis.
The authors concluded that qualitative and quantitative differences in specific bacterial components of the gut microbiome are important features of IBS and its subtypes in children. They propose that the role of generic bacterial overgrowth and, more specifically, small intestinal bacterial overgrowth, be evaluated as mechanism of IBS. However, the total microbial load (the 16S rDNA copy number per gram of stool) did not differ significantly between healthy children and those with IBS.
There were some differences between findings of the 2 studies. For example, although Saulnier et al. reported differences in levels of Proteobacteria between children with IBS and controls, this difference was not observed in adults by Rajilić-Stojanović et al. Likewise, in pediatric patients with IBS, a greater frequency of pain was associated with an increase in the genus Alistipes, but in the adult study, levels of Alistipes were significantly higher in controls. These differences might result from the different patient populations analyzed (pediatric vs adult), geographic regions of the studies (Texas vs Finland), or platforms used (next-generation sequencing and Affymetrix arrays vs Agilent arrays).
In an accompanying editorial, Nicholas Tally and Anthony Fodor suggest that microbial niches in the colon and small intestine might exist—there could be specific differences in the mucosal-associated or the luminal microbiota that contribute to development of diseases such as IBS.
Nonetheless, Talley and Fodor concluded that the application of high-throughput technology to IBS is a first step toward identifying each person’s microbial community and individualizing therapy, perhaps with probiotics, prebiotics, and/or antibiotics.
Saulnier et al. propose that analyses of clinical features, dietary and medication history, and genetics will also help us better understand the genetic, metagenomic, and environmental factors that contribute to IBS and other intestinal disorders.
Read the articles online.
Saulnier DM, Riehle K, Mistret T-A, et al. Gastrointestinal microbiome signatures of pediatric patients with irritable bowel syndrome. Gastroenterology 2011;141:1782–1791.
Rajilić–Stojanović M, Biagi E, Heilig HGHJ, et al. Global and deep molecular analysis of microbiota signatures in fecal samples from patients with irritable bowel syndrome. Gastroenterology2011;141:1792–1801.
Read the accompanying editorial.
Talley NJ, Fodor AA. Bugs, stool, and the irritable bowel syndrome: too much is as bad as too little? Gastroenterology2011;141:1555–1559.