A Pyrosequencing Study in Twins Shows That Gastrointestinal Microbial Profiles Vary With Inflammatory Bowel Disease Phenotypes

Willing, Ben; Dicksved, Johan; Halfvarson, Jonas; Andersson, Anders F.; Lucio, Marianna; Zheng, Zongli; Järnerot, Gunnar; Tysk, Curt; Jansson, Janet; Engstrand, Lars

doi:10.1053/j.gastro.2010.08.049

Cited by 913 publications

(837 citation statements)

References 42 publications

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“…Perhaps of most interest, we demonstrated a signifi cant increase in F. prausnitzii in CD at diagnosis, in marked contrast with previous reports of a reduction in the species in adult CD ( 29,34,35 ).…”

Section: Microbiota Of Pediatric Ibd By Pyrosequencingcontrasting

confidence: 92%

“…Furthermore, the organisms least likely to be aff ected would be those with adherent properties, of most interest in the mucosal disease of IBD. In support of our approach, other investigators have demonstrated diff erences in the IBD microbiota despite prior bowel preparation ( 10,29 ). Finally, a study design where children undergo diagnostic colonoscopy under general anesthetic without adequate preparation would be ethically unacceptable.…”

Section: Discussionmentioning

confidence: 56%

“…Our data using more robust methodology are the fi rst to demonstrate an increase in this bacterium at CD diagnosis, which suggests a more complex and integral role for F. prausnitzii in CD pathogenesis. Interestingly, the data of Willing et al ( 29 ), derived from pyrosequencing of fecal samples in established disease, demonstrated an increase in Faecalibacterium in colonic, but a reduction in ileal CD although the former was not elaborated fully on within the paper.…”

Section: Microbiota Of Pediatric Ibd By Pyrosequencingmentioning

confidence: 95%

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

Hansen

Russell

Reiff³

et al. 2012

American Journal of Gastroenterology

248

180

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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

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Section: Microbiota Of Pediatric Ibd By Pyrosequencingcontrasting

confidence: 92%

Section: Discussionmentioning

confidence: 56%

Section: Microbiota Of Pediatric Ibd By Pyrosequencingmentioning

confidence: 95%

See 1 more Smart Citation

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

Hansen

Russell

Reiff³

et al. 2012

American Journal of Gastroenterology

248

180

View full text Add to dashboard Cite

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“…Moreover, by locally excreting antimicrobials or competing with pathogens, mucosal microbes more effectively limit pathogen translocation. Besides host immune effectors (Lievin-Le Moal and Servin, 2006), microbial properties, such as mucus adhesion (Roos and Jonsson, 2002) or the ability to degrade host-derived glycans (Derrien et al, 2004), also impact the distinct surface-attached microbial composition, generally characterized by an enrichment of Firmicutes (especially Clostridium cluster XIVa) over Bacteroidetes (Eckburg et al, 2005;Frank et al, 2007;Hill et al, 2009;Shen et al, 2010;Willing et al, 2010;Hong et al, 2011;Nava et al, 2011). Moreover, the mucus layer is persistently colonized by all types of hydrogenotrophs: methanogenic archaea, sulphate-reducing bacteria and acetogenic bacteria (Nava et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Butyrate-producing Clostridium cluster XIVa species specifically colonize mucins in an in vitro gut model

et al. 2012

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The human gut is colonized by a complex microbiota with multiple benefits. Although the surfaceattached, mucosal microbiota has a unique composition and potential to influence human health, it remains difficult to study in vivo. Therefore, we performed an in-depth microbial characterization (human intestinal tract chip (HITChip)) of a recently developed dynamic in vitro gut model, which simulates both luminal and mucosal gut microbes (mucosal-simulator of human intestinal microbial ecosystem (M-SHIME)). Inter-individual differences among human subjects were confirmed and microbial patterns unique for each individual were preserved in vitro. Furthermore, in correspondence with in vivo studies, Bacteroidetes and Proteobacteria were enriched in the luminal content while Firmicutes rather colonized the mucin layer, with Clostridium cluster XIVa accounting for almost 60% of the mucin-adhered microbiota. Of the many acetate and/or lactate-converting butyrate producers within this cluster, Roseburia intestinalis and Eubacterium rectale most specifically colonized mucins. These 16S rRNA gene-based results were confirmed at a functional level as butyryl-CoA:acetate-CoA transferase gene sequences belonged to different species in the luminal as opposed to the mucin-adhered microbiota, with Roseburia species governing the mucosal butyrate production. Correspondingly, the simulated mucosal environment induced a shift from acetate towards butyrate. As not only inter-individual differences were preserved but also because compared with conventional models, washout of relevant mucin-adhered microbes was avoided, simulating the mucosal gut microbiota represents a breakthrough in modeling and mechanistically studying the human intestinal microbiome in health and disease. Finally, as mucosal butyrate producers produce butyrate close to the epithelium, they may enhance butyrate bioavailability, which could be useful in treating diseases, such as inflammatory bowel disease.

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“…These supervised selection methods provide a way to integrate metadata or sample labels collected during a study's first stage and to use that stage's data to more specifically target its second stage. Such stratification has been used in case-control studies investigating conditions such as inflammatory bowel disease (Frank et al, 2007;Willing et al, 2010;Morgan et al, 2012), age and geographic origin (Yatsunenko et al, 2012), or simply different body site habitats (The Human Microbiome Project Consortium, 2012b). Any of the unsupervised methods can be applied within multiple such strata.…”

Section: Resultsmentioning

confidence: 99%

Two-stage microbial community experimental design

et al. 2013

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Microbial community samples can be efficiently surveyed in high throughput by sequencing markers such as the 16S ribosomal RNA gene. Often, a collection of samples is then selected for subsequent metagenomic, metabolomic or other follow-up. Two-stage study design has long been used in ecology but has not yet been studied in-depth for high-throughput microbial community investigations. To avoid ad hoc sample selection, we developed and validated several purposive sample selection methods for two-stage studies (that is, biological criteria) targeting differing types of microbial communities. These methods select follow-up samples from large community surveys, with criteria including samples typical of the initially surveyed population, targeting specific microbial clades or rare species, maximizing diversity, representing extreme or deviant communities, or identifying communities distinct or discriminating among environment or host phenotypes. The accuracies of each sampling technique and their influences on the characteristics of the resulting selected microbial community were evaluated using both simulated and experimental data. Specifically, all criteria were able to identify samples whose properties were accurately retained in 318 paired 16S amplicon and whole-community metagenomic (follow-up) samples from the Human Microbiome Project. Some selection criteria resulted in follow-up samples that were strongly non-representative of the original survey population; diversity maximization particularly undersampled community configurations. Only selection of intentionally representative samples minimized differences in the selected sample set from the original microbial survey. An implementation is provided as the microPITA (Microbiomes: Picking Interesting Taxa for Analysis) software for two-stage study design of microbial communities.

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A Pyrosequencing Study in Twins Shows That Gastrointestinal Microbial Profiles Vary With Inflammatory Bowel Disease Phenotypes

Cited by 913 publications

References 42 publications

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

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

Butyrate-producing Clostridium cluster XIVa species specifically colonize mucins in an in vitro gut model

Two-stage microbial community experimental design

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