Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment

• Published in: Genome Biology Vol. 13; no. 9; p. R79
• Main Authors: Morgan, Xochitl C, Tickle, Timothy L, Sokol, Harry, Gevers, Dirk, Devaney, Kathryn L, Ward, Doyle V, Reyes, Joshua A, Shah, Samir A, LeLeiko, Neal, Snapper, Scott B, Bousvaros, Athos, Korzenik, Joshua, Sands, Bruce E, Xavier, Ramnik J, Huttenhower, Curtis
• Format: Journal Article
• Language: English
• Published: England Springer-Verlag 26.09.2012; BioMed Central
• Subjects: amino acid metabolism; Amino Acids; Amino Acids - metabolism; Bacteria; Bacteria - genetics; Bacteria - pathogenicity; Biological Transport; biosynthesis; Carbohydrate Metabolism; Case-Control Studies; Chemical Sciences; colitis; Crohn disease; drug effects; drug therapy; Enterobacteriaceae; environmental factors; feces; Firmicutes; genes; Genes, rRNA; genetics; Humans; ileum; immune system; Inflammatory Bowel Diseases; Inflammatory Bowel Diseases - drug therapy; Inflammatory Bowel Diseases - microbiology; intestinal microorganisms; Intestines; Intestines - microbiology; Linear Models; metabolism; Metagenome; Metagenome - drug effects; Metagenome - genetics; Metagenomics; microbiology; Multivariate Analysis; nutrient transport; Organic chemistry; Oxidative Stress; pathogenesis; pathogenicity; Phylogeny; RNA, Ribosomal, 16S; RNA, Ribosomal, 16S - genetics; secretion; sequence analysis; Sequence Analysis, DNA; virulence
• ISSN: 1465-6906; 1474-760X; 1465-6914; 1474-760X
• DOI: 10.1186/gb-2012-13-9-r79

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.