9 research outputs found

    Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases.

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    Inflammatory bowel diseases, which include Crohn's disease and ulcerative colitis, affect several million individuals worldwide. Crohn's disease and ulcerative colitis are complex diseases that are heterogeneous at the clinical, immunological, molecular, genetic, and microbial levels. Individual contributing factors have been the focus of extensive research. As part of the Integrative Human Microbiome Project (HMP2 or iHMP), we followed 132 subjects for one year each to generate integrated longitudinal molecular profiles of host and microbial activity during disease (up to 24 time points each; in total 2,965 stool, biopsy, and blood specimens). Here we present the results, which provide a comprehensive view of functional dysbiosis in the gut microbiome during inflammatory bowel disease activity. We demonstrate a characteristic increase in facultative anaerobes at the expense of obligate anaerobes, as well as molecular disruptions in microbial transcription (for example, among clostridia), metabolite pools (acylcarnitines, bile acids, and short-chain fatty acids), and levels of antibodies in host serum. Periods of disease activity were also marked by increases in temporal variability, with characteristic taxonomic, functional, and biochemical shifts. Finally, integrative analysis identified microbial, biochemical, and host factors central to this dysregulation. The study's infrastructure resources, results, and data, which are available through the Inflammatory Bowel Disease Multi'omics Database ( http://ibdmdb.org ), provide the most comprehensive description to date of host and microbial activities in inflammatory bowel diseases

    A novel Ruminococcus gnavus clade enriched in inflammatory bowel disease patients

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    Background: Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract that is associated with changes in the gut microbiome. Here, we sought to identify strain-specific functional correlates with IBD outcomes. Methods: We performed metagenomic sequencing of monthly stool samples from 20 IBD patients and 12 controls (266 total samples). These were taxonomically profiled with MetaPhlAn2 and functionally profiled using HUMAnN2. Differentially abundant species were identified using MaAsLin and strain-specific pangenome haplotypes were analyzed using PanPhlAn. Results: We found a significantly higher abundance in patients of facultative anaerobes that can tolerate the increased oxidative stress of the IBD gut. We also detected dramatic, yet transient, blooms of Ruminococcus gnavus in IBD patients, often co-occurring with increased disease activity. We identified two distinct clades of R. gnavus strains, one of which is enriched in IBD patients. To study functional differences between these two clades, we augmented the R. gnavus pangenome by sequencing nine isolates from IBD patients. We identified 199 IBD-specific, strain-specific genes involved in oxidative stress responses, adhesion, iron-acquisition, and mucus utilization, potentially conferring an adaptive advantage for this R. gnavus clade in the IBD gut. Conclusions: This study adds further evidence to the hypothesis that increased oxidative stress may be a major factor shaping the dysbiosis of the microbiome observed in IBD and suggests that R. gnavus may be an important member of the altered gut community in IBD. Electronic supplementary material The online version of this article (doi:10.1186/s13073-017-0490-5) contains supplementary material, which is available to authorized users

    Additional file 6: Figure S1. of A novel Ruminococcus gnavus clade enriched in inflammatory bowel disease patients

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    Pangenome analysis on two distinct clades of R. gnavus. Pangenome analysis of R. gnavus using PanPhlAn showing the presence or absence of every gene in the R. gnavus pangenome. The x-axis shows metagenomic samples as well as R. gnavus reference genomes; the y-axis shows gene clusters from the R. gnavus pangenome. Clustering the results reveals two clades of R. gnavus, which we call clade 1 and clade 2. Using metagenomic samples from LSS/Lewis/HMP cohorts, we found that R. gnavus strains from all healthy adult controls and some IBD samples were functionally similar to R. gnavus clade 1. On the other hand, only IBD samples had R. gnavus strains which were functionally similar to R. gnavus clade 2. The red transparent rectangle contains genes enriched in R. gnavus group IBD. The green transparent rectangle contains genes many genes missing from R. gnavus group IBD. (PDF 2396 kb
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