title: Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment.
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.
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Xochitl C
authors.initials: XC
authors.lastname: Morgan
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Tickle
authors.forename: Harry
authors.initials: H
authors.lastname: Sokol
authors.forename: Dirk
authors.initials: D
authors.lastname: Gevers
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Devaney
authors.forename: Doyle V
authors.initials: DV
authors.lastname: Ward
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Reyes
authors.forename: Samir A
authors.initials: SA
authors.lastname: Shah
authors.forename: Neal
authors.initials: N
authors.lastname: LeLeiko
authors.forename: Scott B
authors.initials: SB
authors.lastname: Snapper
authors.forename: Athos
authors.initials: A
authors.lastname: Bousvaros
authors.forename: Joshua
authors.initials: J
authors.lastname: Korzenik
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Sands
authors.forename: Ramnik J
authors.initials: RJ
authors.lastname: Xavier
authors.forename: Curtis
authors.initials: C
authors.lastname: Huttenhower
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D001419:Bacteria / Q000235:genetics* / Q000472:pathogenicity; D001692:Biological Transport; D050260:Carbohydrate Metabolism; D016022:Case-Control Studies; D020459:Genes, rRNA; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000382:microbiology*; D007422:Intestines / Q000382:microbiology*; D016014:Linear Models; D054892:Metagenome / Q000187:drug effects / Q000235:genetics*; D056186:Metagenomics; D015999:Multivariate Analysis; D018384:Oxidative Stress; D010802:Phylogeny; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D017422:Sequence Analysis, DNA
chemical_list: D000596:Amino Acids; D012336:RNA, Ribosomal, 16S