Microbiota of De-Novo Pediatric IBD: Increased Faecalibacterium Prausnitzii and Reduced Bacterial Diversity in Crohn's But Not in Ulcerative Colitis

Abstract

The gastrointestinal microbiota is considered important in infl ammatory bowel disease (IBD) pathogenesis. Discoveries from established disease cohorts report reduced bacterial diversity, changes in bacterial composition, and a protective role for Faecalibacterium prausnitzii in Crohn ' s disease (CD). The majority of studies to date are however potentially confounded by the effect of treatment and a reliance on established rather than de-novo disease. METHODS:Microbial changes at diagnosis were examined by biopsying the colonic mucosa of 37 children: 25 with newly presenting, untreated IBD with active colitis (13 CD and 12 ulcerative colitis (UC)), and 12 pediatric controls with a macroscopically and microscopically normal colon. We utilized a dual-methodology approach with pyrosequencing (threshold >10,000 reads) and confi rmatory real-time PCR (RT-PCR). RESULTS:Threshold pyrosequencing output was obtained on 34 subjects (11 CD, 11 UC, 12 controls). No signifi cant changes were noted at phylum level among the Bacteroidetes, Firmicutes, or Proteobacteria. A signifi cant reduction in bacterial α -diversity was noted in CD vs. controls by three methods (Shannon, Simpson, and phylogenetic diversity) but not in UC vs. controls. An increase in Faecalibacterium was observed in CD compared with controls by pyrosequencing (mean 16.7 % vs. 9.1 % of reads, P = 0.02) and replicated by specifi c F. prausnitzii RT-PCR (36.0 % vs. 19.0 % of total bacteria, P = 0.02). No disease-specifi c clustering was evident on principal components analysis. CONCLUSIONS: Our results offer a comprehensive examination of the IBD mucosal microbiota at diagnosis, unaffected by therapeutic confounders or changes over time. Our results challenge the current model of a protective role for F. prausnitzii in CD, suggesting a more dynamic role for this organism than previously described.SUPPLEMENTARY MATERIAL is linked to the online version of the paper at

Impact of short-chain galactooligosaccharides on the gut microbiome of lactose-intolerant individuals

“…Given their widespread association with a variety of different environments, including dairy, meat, vegetable, and grain-fermented foods and as commensals in the gastrointestinal tract, this genus has been widely consumed and also has been used in dietary supplements to promote general health and well-being (21)(22)(23). Recent human microbiome studies have identified Faecalibacterium prausnitzii as an organism with antiinflammatory properties and have reported it to be an indicator microbial population that was lowered in subjects with Crohn's disease and ulcerative colitis (10,24). In addition to GOS, reported herein, Faecalibacterium also has been shown to be stimulated by the fructooligosaccharide inulin, and specific strains are reported to grow in host-derived substrates such as N-acetylglucosamine (25).…”

“…Genera in cluster I, interpreted as taxa suppressed by GOS and dairy, included genera in Enterobacteriaceae, Streptococcus, Clostridium, Lachnospira, Anaerotruncus, Ruminococcus, and others. Cluster II, interpreted as taxa enhanced in the long term by GOS, included the health-promoting genera Lactobacillus and Faecalibacterium; the latter was found at lower population levels in individuals with inflammatory bowel diseases (9,10). Also enhanced in population were Christensenellaceae (Christensenellaceae_other), a poorly defined family enriched in individuals with a low body mass index (BMI).…”

Automated and accurate estimation of gene family abundance from shotgun metagenomes

“…A permutational multivariate analysis of variance (adonis) quantified the reported p-values for the null hypothesis that the PCA axes are not different by group based on 1e4 permutations. These trends are also observed in an independent analysis of the MetaHIT cohort (S11 Fig). research on separate cohorts also found that the community structure of biopsy-associated microbiomes [46][47][48] differed substantially between UC and CD patients, with UC appearing more like controls in the latter two; one study also saw similar trends in functional annotation from shallow shotgun sequencing [46]. UC and CD can also be differentiated serologically, with UC tending to be characterized more by autoantibodies directed at host neutrophils [49] [50], though these may arise through cross-reactivity with microbial proteins like OmpC [51], and CD being characterized more by antibodies against cell-surface glycans [52], Saccharomyces cerevisiae [50], and proteins such as flagellin [53].…”

Functional metagenomic discovery of bacterial effectors in the human microbiome and isolation of commendamide, a GPCR G2A/132 agonist

“…To ensure we capture the greatest diversity of bacterial species and their encoded effector functions in our metagenomic library collection, we created metagenomic libraries using DNA isolated from the stool of a healthy patient, a patient with Crohn's disease, and a patient with ulcerative colitis. Crohn's disease and ulcerative colitis are collectively known as inflammatory bowel disease (IBD), and bacterial populations in each of these diseases are unique relative to each other and to patients without IBD (12,(27)(28)(29).…”