Colonic Bacteria Express an Ulcerative Colitis pANCA-Related Protein Epitope

Cohavy, Offer; Bruckner, David A.; Gordon, Lynn K.; Misra, Rajeev; Wei, Bo; Eggena, Mark; Targan, Stephan R.; Braun, Jonathan

doi:10.1128/iai.68.3.1542-1548.2000

Cited by 184 publications

(110 citation statements)

References 53 publications

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“…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]. This difference in the antigens associated with CD vs. UC may relate in part to biomolecules made and presented by the gut flora.…”

Section: Accurate Metagenome Annotation Clarifies Community Functionamentioning

confidence: 99%

Automated and accurate estimation of gene family abundance from shotgun metagenomes

Nayfach

Bradley

Wyman

et al. 2015

Preprint

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Shotgun metagenomic DNA sequencing is a widely applicable tool for characterizing the functions that are encoded by microbial communities. Several bioinformatic tools can be used to functionally annotate metagenomes, allowing researchers to draw inferences about the functional potential of the community and to identify putative functional biomarkers. However, little is known about how decisions made during annotation affect the reliability of the results. Here, we use statistical simulations to rigorously assess how to optimize annotation accuracy and speed, given parameters of the input data like read length and library size. We identify best practices in metagenome annotation and use them to guide the development of the Shotgun Metagenome Annotation Pipeline (ShotMAP). ShotMAP is an analytically flexible, end-to-end annotation pipeline that can be implemented either on a local computer or a cloud compute cluster. We use ShotMAP to assess how different annotation databases impact the interpretation of how marine metagenome and metatranscriptome functional capacity changes across seasons. We also apply ShotMAP to data obtained from a clinical microbiome investigation of inflammatory bowel disease. This analysis finds that gut microbiota collected from Crohn's disease patients are functionally distinct from gut microbiota collected from either ulcerative colitis patients or healthy controls, with differential abundance of metabolic pathways related to host-microbiome interactions that may serve as putative biomarkers of disease. Author SummaryMicrobial communities perform a wide variety of functions, from marine photosynthesis to aiding digestion in the human gut. Shotgun "metagenomic" sequencing can be used to sample millions of short DNA sequences from such communities directly, without needing to first culture its constituents in the laboratory. Using these data, researchers can survey which functions are encoded by mapping these short sequences to known protein families and pathways. Several tools for this annotation already exist. But, annotation is a multi-step process that includes identification of genes in a metagenome and determination of the type of protein each gene encodes. We currently know little about how different choices of parameters during annotation influences the final results. In this work, we systematically test how several key decisions affect the accuracy and speed of annotation, and based on these results, develop new software for annotation, which we named ShotMAP. We then use ShotMAP to functionally characterize marine communities and gut communities in a clinical cohort of inflammatory bowel disease. We find several functions are differentially represented in the gut microbiome of Crohn's disease patients, which could be candidates for biomarkers and could also offer insight into the pathophysiology of Crohn's. ShotMAP is freely available (https://github.com/sharpton/shotmap).

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Section: Accurate Metagenome Annotation Clarifies Community Functionamentioning

confidence: 99%

Automated and accurate estimation of gene family abundance from shotgun metagenomes

Nayfach

Bradley

Wyman

et al. 2015

Preprint

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“…22, 23 While serum pANCA and ASCA are the best studied serologic markers for IBD, antibodies against the outer membrane porin C (anti-OmpC) of Escherichia coli and anti-CBir1 are also found in about 50 percent of patients with CD and to a lesser degree in UC patients. 24,25 The value of these disease markers in predicting CD development after IPAA has not been defined.…”

Section: Serologic Immune Markers Have Been Associated With Inflammatmentioning

confidence: 99%

Family History and Serology Predict Crohn's Disease after Ileal Pouch-Anal Anastomosis for Ulcerative Colitis

Melmed¹,

Fleshner²,

Bardakcioglu³

et al. 2008

Diseases of the Colon &Amp; Rectum

110

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Purpose-About 5 to 10 percent of patients undergoing ileal pouch-anal anastomosis with a diagnosis of ulcerative colitis are subsequently diagnosed with Crohn's disease. Preoperative predictors for Crohn's disease post-ileal pouch anal-anastomosis have not been prospectively defined.Methods-Two hundred thirty-eight consecutive patients with ulcerative colitis or indeterminate colitis undergoing ileal pouch anal-anastomosis were prospectively enrolled into a longitudinal database. Clinical factors were assessed perioperatively. Serum drawn pre-operatively was assayed for anti-Saccharomyces-cerevisiae, anti-outer membrane porin-C, anti-CBir1, and perinuclear antineutrophil cytoplasmic antibody using enzyme-linked immunosorbent assay. Crohn's disease was defined by small-bowel inflammation proximal to the ileal pouch or a perianal fistula identified at least 3 months after ileostomy closure. Predictors were assessed in a multivariate Cox proportional hazards model to predict the rate of Crohn's disease after ileostomy closure.

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“…The pANCA (perinuclear antineutrophil cytoplasmic antibody) autoantibody, which is di-rected against neutrophil proteins, cross-reacted with a microbial antigen epitope in E. coli and Bacteroides (64). In E. coli, the epitope was located on the OmpC protein, one of the well-characterized porin proteins.…”

Section: Infections In Adultsmentioning

confidence: 99%

Bacteroides: the Good, the Bad, and the Nitty-Gritty

2007

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SUMMARY Summary: Bacteroides species are significant clinical pathogens and are found in most anaerobic infections, with an associated mortality of more than 19%. The bacteria maintain a complex and generally beneficial relationship with the host when retained in the gut, but when they escape this environment they can cause significant pathology, including bacteremia and abscess formation in multiple body sites. Genomic and proteomic analyses have vastly added to our understanding of the manner in which Bacteroides species adapt to, and thrive in, the human gut. A few examples are (i) complex systems to sense and adapt to nutrient availability, (ii) multiple pump systems to expel toxic substances, and (iii) the ability to influence the host immune system so that it controls other (competing) pathogens. B. fragilis, which accounts for only 0.5% of the human colonic flora, is the most commonly isolated anaerobic pathogen due, in part, to its potent virulence factors. Species of the genus Bacteroides have the most antibiotic resistance mechanisms and the highest resistance rates of all anaerobic pathogens. Clinically, Bacteroides species have exhibited increasing resistance to many antibiotics, including cefoxitin, clindamycin, metronidazole, carbapenems, and fluoroquinolones (e.g., gatifloxacin, levofloxacin, and moxifloxacin).

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Colonic Bacteria Express an Ulcerative Colitis pANCA-Related Protein Epitope

Cited by 184 publications

References 53 publications

Automated and accurate estimation of gene family abundance from shotgun metagenomes

Automated and accurate estimation of gene family abundance from shotgun metagenomes

Family History and Serology Predict Crohn's Disease after Ileal Pouch-Anal Anastomosis for Ulcerative Colitis

Bacteroides: the Good, the Bad, and the Nitty-Gritty

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