Summary of project PR000677
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000677. The data can be accessed directly via it's Project DOI: 10.21228/M85H44 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR000677 |
| Project DOI: | doi: 10.21228/M85H44 |
| Project Title: | Gut microbiome structure and metabolic activity in inflammatory bowel disease |
| Project Summary: | The inflammatory bowel diseases (IBD), which include Crohn’s disease (CD) and ulcerative colitis (UC), are multifactorial, chronic conditions of the gastrointestinal tract. While IBD has been associated with dramatic changes in the gut microbiota, changes in the gut metabolome -- the molecular interface between host and microbiota -- are less-well understood. To address this gap, we performed untargeted LC-MS metabolomic and shotgun metagenomic profiling of cross-sectional stool samples from discovery (n=155) and validation (n=65) cohorts of CD, UC, and non-IBD control subjects. Metabolomic and metagenomic profiles were broadly correlated with fecal calprotectin levels (a measure of gut inflammation). Across >8,000 measured metabolite features, we identified chemicals and chemical classes that were differentially abundant (DA) in IBD, including enrichments for sphingolipids and bile acids, and depletions for triacylglycerols and tetrapyrroles. While >50% of DA metabolite features were uncharacterized, many could be assigned putative roles through metabolomic “guilt-by-association” (covariation with known metabolites). DA species and functions from the metagenomic profiles reflected adaptation to oxidative stress in the IBD gut, and were individually consistent with previous findings. Integrating these data, however, we identified 122 robust associations between DA species and well-characterized DA metabolites, indicating possible mechanistic relationships that are perturbed in IBD. Finally, we found that metabolome- and metagenome-based classifiers of IBD status were highly accurate and, like the vast majority of individual trends, generalized well to the independent validation cohort. Our findings thus provide an improved understanding of perturbations of the microbiome-metabolome interface in IBD, including identification of many potential diagnostic and therapeutic targets. |
| Institute: | Broad Institute of MIT and Harvard |
| Department: | Metabolomics Platform |
| Last Name: | Avila-Pacheco |
| First Name: | Julian |
| Address: | 415 Main Street, Cambridge MA |
| Email: | jravilap@broadinstitute.org |
| Phone: | 617-714-8264 |
| Contributors: | Eric A. Franzosa, Alexandra Sirota-Madi, Julian Avila-Pacheco, Nadine Fornelos, Henry J. Haiser, Stefan Reinker, Tommi Vatanen, A. Brantley Hall, Himel Mallick, Lauren J. McIver, Jenny S. Sauk, Robin G. Wilson, Betsy W. Stevens, Justin M. Scott, Kerry Pierce, Amy A. Deik, Kevin Bullock, Floris Imhann, Jeffrey Porter, Alexandra Zhernakova, Jingyuan Fu,7, Rinse K. Weersma, Cisca Wijmenga, Clary B. Clish, Hera Vlamakis, Curtis Huttenhower, Ramnik J. Xavier |
Summary of all studies in project PR000677
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST001000 | Gut microbiome structure and metabolic activity in inflammatory bowel disease | Homo sapiens | Broad Institute of MIT and Harvard | MS* | 2019-04-17 | 1 | 220 | Uploaded data (105.3G)* |
