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PMID: 23013615 Published · epublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment.

Genome biology ·Vol. 13 ·No. 9 ·2012-04-16 ·Pages R79

Morgan XC, Tickle TL, Sokol H, Gevers D, Devaney KL, Ward DV, Reyes JA, Shah SA, LeLeiko N, Snapper SB, Bousvaros A, Korzenik J, Sands BE, Xavier RJ, Huttenhower C

Abstract

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. 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. This inferred functional metagenomic information provides the first insights into community-wide microbial processes and pathways that underpin IBD pathogenesis.

MeSH Terms
Amino Acids/metabolism Bacteria/genetics,pathogenicity Biological Transport Carbohydrate Metabolism Case-Control Studies Genes, rRNA Humans Inflammatory Bowel Diseases/drug therapy,microbiology Intestines/microbiology Linear Models Metagenome/drug effects,genetics Metagenomics Multivariate Analysis Oxidative Stress Phylogeny RNA, Ribosomal, 16S/genetics Sequence Analysis, DNA
Chemicals
Amino Acids RNA, Ribosomal, 16S
Authors & Affiliations
15 authors, click to expand affiliations / ORCID
Morgan Xochitl C
Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA.
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
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Article Info
Journal
Genome biology
Abbr.
Genome Biol
ISSN
1474-760X
DOI
10.1186/gb-2012-13-9-r79
Published
2012-04-16
Epub
2012-00-16
Pages
R79
Language
English
Region
England
NLM ID
100960660
PMCID
PMC3506950
Subset
IM
Grants
NHGRI NIH HHS · U54HG004969 · United States
NIDDK NIH HHS · P30 DK043351 · United States
NIDDK NIH HHS · R01 DK092405 · United States
NIGMS NIH HHS · T32 GM080177 · United States
NHGRI NIH HHS · 1R01HG005969 · United States
NICHD NIH HHS · 1R21HD058828-01A1 · United States
Corrections
CommentIn
PMID: 23013527
External Links
PubMed source DOI: 10.1186/gb-2012-13-9-r79 PMC Full Text View journal details
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