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Integrated Metagenomics/Metaproteomics Reveals Human Host-Microbiota Signatures of Crohn's Disease
Authors:Alison R. Erickson  Brandi L. Cantarel  Regina Lamendella  Youssef Darzi  Emmanuel F. Mongodin  Chongle Pan  Manesh Shah  Jonas Halfvarson  Curt Tysk  Bernard Henrissat  Jeroen Raes  Nathan C. Verberkmoes  Claire M. Fraser  Robert L. Hettich  Janet K. Jansson
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.
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