title: Integrated metagenomics/metaproteomics reveals human host-microbiota signatures of Crohn's disease.
abstract: Crohn's disease (CD) is an inflammatory bowel disease of complex etiology, although dysbiosis of the gut microbiota has been implicated in chronic immune-mediated inflammation associated with CD. Here we combined shotgun metagenomic and metaproteomic approaches to identify potential functional signatures of CD in stool samples from six twin pairs that were either healthy, or that had CD in the ileum (ICD) or colon (CCD). Integration of these omics approaches revealed several genes, proteins, and pathways that primarily differentiated ICD from healthy subjects, including depletion of many proteins in ICD. In addition, the ICD phenotype was associated with alterations in bacterial carbohydrate metabolism, bacterial-host interactions, as well as human host-secreted enzymes. This eco-systems biology approach underscores the link between the gut microbiota and functional alterations in the pathophysiology of Crohn's disease and aids in identification of novel diagnostic targets and disease specific biomarkers.
authors.affiliation: Chemical Science Division, Oak Ridge National Laboratory, Oak Ridge, TN, USA.
authors.forename: Alison R
authors.initials: AR
authors.lastname: Erickson
authors.forename: Brandi L
authors.initials: BL
authors.lastname: Cantarel
authors.forename: Regina
authors.initials: R
authors.lastname: Lamendella
authors.forename: Youssef
authors.initials: Y
authors.lastname: Darzi
authors.forename: Emmanuel F
authors.initials: EF
authors.lastname: Mongodin
authors.forename: Chongle
authors.initials: C
authors.lastname: Pan
authors.forename: Manesh
authors.initials: M
authors.lastname: Shah
authors.forename: Jonas
authors.initials: J
authors.lastname: Halfvarson
authors.forename: Curt
authors.initials: C
authors.lastname: Tysk
authors.forename: Bernard
authors.initials: B
authors.lastname: Henrissat
authors.forename: Jeroen
authors.initials: J
authors.lastname: Raes
authors.forename: Nathan C
authors.initials: NC
authors.lastname: Verberkmoes
authors.forename: Claire M
authors.initials: CM
authors.lastname: Fraser
authors.forename: Robert L
authors.initials: RL
authors.lastname: Hettich
authors.forename: Janet K
authors.initials: JK
authors.lastname: Jansson
mesh_terms: D001419:Bacteria / Q000235:genetics / Q000378:metabolism; D016000:Cluster Analysis; D003424:Crohn Disease / Q000378:metabolism* / Q000382:microbiology*; D005260:Female; D041981:Gastrointestinal Tract / Q000378:metabolism / Q000382:microbiology; D006801:Humans; D007082:Ileum / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D007413:Intestinal Mucosa / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D008297:Male; D053858:Metabolic Networks and Pathways; D054892:Metagenome; D056186:Metagenomics; D020543:Proteome; D040901:Proteomics; D014430:Twins, Monozygotic
chemical_list: D020543:Proteome