Gastrointestinal Microbiome Signatures of Pediatric Patients With Irritable Bowel Syndrome

Abstract

BACKGROUND AND AIMS The intestinal microbiomes of healthy children and pediatric patients with irritable bowel syndrome (IBS) are not well defined. Studies in adults have indicated that the gastrointestinal microbiota could be involved in IBS. METHODS We analyzed 71 samples from 22 children with IBS (pediatric Rome III criteria) and 22 healthy children, ages 7–12 years, by 16S rRNA gene sequencing, with an average of 54,287 reads/stool sample (average 454 read length = 503 bases). Data were analyzed using phylogenetic-based clustering (Unifrac), or an operational taxonomic unit (OTU) approach using a supervised machine learning tool (randomForest). Most samples were also hybridized to a microarray that can detect 8,741 bacterial taxa (16S rRNA PhyloChip). RESULTS Microbiomes associated with pediatric IBS were characterized by a significantly greater percentage of the class Gammaproteobacteria (0.07% vs 0.89% of total bacteria; P <.05); one prominent component of this group was Haemophilus parainfluenzae. Differences highlighted by 454 sequencing were confirmed by high-resolution PhyloChip analysis. Using supervised learning techniques, we were able to classify different subtypes of IBS with a success rate of 98.5%, using limited sets of discriminant bacterial species. A novel Ruminococcus-like microbe was associated with IBS, indicating the potential utility of microbe discovery for gastrointestinal disorders. A greater frequency of pain correlated with an increased abundance of several bacterial taxa from the genus Alistipes. CONCLUSIONS Using16S metagenomics by Phylochip DNA hybridization and deep 454 pyrosequencing, we associated specific microbiome signatures with pediatric IBS. These findings indicate the important association between gastrointestinal microbes and IBS in children; these approaches might be used in diagnosis of functional bowel disorders in pediatric patients.

Secretory antibodies in breast milk promote long-term intestinal homeostasis by regulating the gut microbiota and host gene expression

“…We observed certain parallels between the altered microbiota of mice that did not receive passive SIgA in breast milk and the microbiota of IBD patients. Our finding of increased abundance of bacterial taxa in the families Pasteurellaceae (phylum Proteobacteria) and Lachnospiraceae (phylum Firmicutes) in weanling mice deprived of passive SIgA is not unlike the increase in taxa from these families observed in the gut microbiota of pediatric IBD patients (32). Our finding of a striking increase of unique bacterial taxa in the family Comamonadaceae (phylum Proteobacteria) in weanling mice deprived of passive SIgA may be significant in light of the report documenting increased numbers of Comamonadaceae in the microbiota of IBD patients with chronic pouchitis (33).…”

Patterned progression of bacterial populations in the premature infant gut

“…Second, the overall bacterial composition is largely limited to three classes, and their distribution contrasts markedly with gut bacterial composition in older children and adults. Specifically, Bacilli, Gammaproteobacteria, and Clostridia represent 1-5%, <1%, and 45-80%, of all classes, respectively (21,22), in later life compared with the corresponding proportions (19.3%, 54.0%, and 18.5%, respectively) in study infants. Third, maturation of the gut bacterial population structure is punctuated by abrupt shifts in microbial composition.…”

The role of early life nutrition in the establishment of gastrointestinal microbial composition and function

“…4 The microbiota acquired in early life have longterm implications for host metabolism and gastrointestinal (GI), immune and neurological function. 5,6 Reduced diversity or dysbiosis are linked to childhood and later life disorders, including necrotizing enterocolitis, 7 eczema, 8 asthma, 9 inflammatory bowel diseases, 10 irritable bowel syndrome, 11 obesity, 12 diabetes 13 and autism. 14 Diet is one of the major determinants of GI microbial diversity.…”