Accession Number : ADA606924


Title :   Dysfunction of the Intestinal Microbiome in Inflammatory Bowel Disease and Treatment


Descriptive Note : Journal article


Corporate Author : HARVARD SCHOOL OF PUBLIC HEALTH BOSTON MA


Personal Author(s) : Morgan, Xochitl C ; Tickle, Timothy L ; Sokol, Harry ; Gevers, Dirk ; Debaney, Kathryn L ; Ward, Doyle V ; Reyes, Jashua A ; Shah, Samir A ; LeLeiko, Neal ; Snapper, Scott B


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a606924.pdf


Report Date : Jan 2012


Pagination or Media Count : 21


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.


Descriptors :   *GASTROINTESTINAL DISEASES , *INFLAMMATION , AMINO ACIDS , BIOPSY , BIOSYNTHESIS , CARBOHYDRATE METABOLISM , COLITIS , CULTURES(BIOLOGY) , DYSFUNCTION , ENTEROBACTERIACEAE , FECES , GENES , ILEUM , METABOLISM , MICROORGANISMS , NUTRIENTS , REPRINTS , SECRETION , VIRULENCE


Subject Categories : Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE