Gut microbiome structure and metabolic activity in inflammatory bowel disease.

Autor: Franzosa EA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA., Sirota-Madi A; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Avila-Pacheco J; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Fornelos N; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Haiser HJ; Novartis Institute for Biomedical Research Inc., Cambridge, MA, USA., Reinker S; Novartis Institute for Biomedical Research Inc., Cambridge, MA, USA., Vatanen T; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Hall AB; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Mallick H; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA., McIver LJ; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA., Sauk JS; Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Wilson RG; Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Stevens BW; Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Scott JM; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Pierce K; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Deik AA; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Bullock K; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Imhann F; Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.; Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands., Porter JA; Novartis Institute for Biomedical Research Inc., Basel, Switzerland., Zhernakova A; Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands., Fu J; Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.; Department of Pediatrics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands., Weersma RK; Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands., Wijmenga C; Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.; Department of Immunology, K.G. Jebsen Coeliac Disease Research Centre, University of Oslo, Oslo, Norway., Clish CB; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Vlamakis H; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Huttenhower C; Broad Institute of MIT and Harvard, Cambridge, MA, USA. chuttenh@hsph.harvard.edu.; Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA. chuttenh@hsph.harvard.edu., Xavier RJ; Broad Institute of MIT and Harvard, Cambridge, MA, USA. xavier@molbio.mgh.harvard.edu.; Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. xavier@molbio.mgh.harvard.edu.; Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, MA, USA. xavier@molbio.mgh.harvard.edu.
Jazyk: angličtina
Zdroj: Nature microbiology [Nat Microbiol] 2019 Feb; Vol. 4 (2), pp. 293-305. Date of Electronic Publication: 2018 Dec 10.
DOI: 10.1038/s41564-018-0306-4
Abstrakt: The inflammatory bowel diseases (IBDs), 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 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 patients. Metabolomic and metagenomic profiles were broadly correlated with faecal calprotectin levels (a measure of gut inflammation). Across >8,000 measured metabolite features, we identified chemicals and chemical classes that were differentially abundant in IBD, including enrichments for sphingolipids and bile acids, and depletions for triacylglycerols and tetrapyrroles. While > 50% of differentially abundant metabolite features were uncharacterized, many could be assigned putative roles through metabolomic 'guilt by association' (covariation with known metabolites). Differentially abundant 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 differentially abundant species and well-characterized differentially abundant 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.
Databáze: MEDLINE
Externí odkaz: