Year: 2012
Type: article
Study design: Observational Study
Abstract: BACKGROUND: The inflammatory bowel diseases (IBD) Crohn's disease and ulcerative colitis result from alterations in intestinal microbes and the immune system. However, the precise dysfunctions of microbial metabolism in the gastrointestinal microbiome during IBD remain unclear. We analyzed the microbiota of intestinal biopsies and stool samples from 231 IBD and healthy subjects by 16S gene pyrosequencing and followed up a subset using shotgun metagenomics. Gene and pathway composition were assessed, based on 16S data from phylogenetically-related reference genomes, and associated using sparse multivariate linear modeling with medications, environmental factors, and IBD status. RESULTS: Firmicutes and Enterobacteriaceae abundances were associated with disease status as expected, but also with treatment and subject characteristics. Microbial function, though, was more consistently perturbed than composition, with 12% of analyzed pathways changed compared with 2% of genera. We identified major shifts in oxidative stress pathways, as well as decreased carbohydrate metabolism and amino acid biosynthesis in favor of nutrient transport and uptake. The microbiome of ileal Crohn's disease was notable for increases in virulence and secretion pathways. CONCLUSIONS: This inferred functional metagenomic information provides the first insights into community-wide microbial processes and pathways that underpin IBD pathogenesis.
Source: Genome biology
Institutions: Harvard University, Broad Institute, Massachusetts Institute of Technology, Massachusetts General Hospital, Center for Computational and Integrative Biology, Massachusetts General Hospital, Brown University, Hasbro Children's Hospital, Brigham and Women's Hospital, Icahn School of Medicine at Mount Sinai
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,490
Funders: National Science Foundation, Crohn's and Colitis Foundation of America, Brigham and Women's Hospital, Massachusetts General Hospital, Brown University, Massachusetts Institute of Technology, Harvard University, Crohn's and Colitis Foundation, Broad Institute, Philippe Foundation, Fondation Bettencourt Schueller, National Institutes of Health, Centers for Disease Control and Prevention, National Human Genome Research Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, Division of Biological Infrastructure, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Army Research Office
Awards: G1491431696, G245281569, Autophagy genes and the microbiome in Crohn's Disease, G2656861133, Functional activity and inter-organismal interactions in the human microbiome, G4001477574, G4332275241, G4525611964, G5424192119, CAREER: Scalable Computational Models for Multicellular Systems Biology, G6274946069, G7452299184, Development of the Pediatric IBD Behavioral Health Registry, G862988727, Harvard Systems Biology Graduate Program, Center for the Study of Inflammatory Bowel Disease at Massachusetts General Hospital
OpenAlex ID: W2143777796