ibd2012

Dysfunction of the Intestinal Microbiome in Inflammatory Bowel Disease and Treatment

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 in 16S data on 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.


 

If you find this data or analysis useful, please cite our paper:

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. "Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment." Genome Biology 2012 Apr 16;13(9):R79

* co-first authors

 

Study Metadata: osccar_prism_metadata.txt

454 V3-5 16S amplicon sequencing data
Run Barcodes
GLXK8YI01.sff.zip GLXK8YI01.txt
GLXK8YI02.sff.zip GLXK8YI02.txt
GNKV64B01.sff.zip GNKV64B01.txt

 

Illumina MiSeq shotgun metagenomic data
Subject (phenotype) Paired end 1 Paired end 2
7870 (Healthy) 1 2
7862 (Healthy) 1 2
7861 (Healthy) 1 2
7860 (Healthy) 1 2
7855 (Healthy) 1 2
7848 (Healthy) 1 2
7844 (Healthy) 1 2
100225 (CD) 1 2
100217 (CD) 1 2
100198 (CD) 1 2
100176 (CD) 1 2