Integrated Metagenomics/Metaproteomics Reveals Human Host-Microbiota Signatures of Crohn's Disease

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...

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Vydáno v:	PloS one Ročník 7; číslo 11; s. e49138
Hlavní autoři:	Erickson, Alison R., Cantarel, Brandi L., Lamendella, Regina, Darzi, Youssef, Mongodin, Emmanuel F., Pan, Chongle, Shah, Manesh, Halfvarson, Jonas, Tysk, Curt, Henrissat, Bernard, Raes, Jeroen, Verberkmoes, Nathan C., Fraser, Claire M., Hettich, Robert L., Jansson, Janet K.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Public Library of Science 28.11.2012 Public Library of Science (PLoS)
Témata:	Acids Acquired immune deficiency syndrome AIDS Bacteria Bacteria - genetics Bacteria - metabolism Bioengineering Bioindicators Bioinformatics Biology Biomarkers Carbohydrate metabolism Carbohydrates Cluster Analysis Colon Crohn Disease - metabolism Crohn Disease - microbiology Crohn's Disease Crohns disease Development and progression Diagnostic systems Dysbacteriosis Earth science Etiology Female Gastroenterology Gastrointestinal diseases Gastrointestinal Tract - metabolism Gastrointestinal Tract - microbiology Genomes Humans Ileum Ileum - metabolism Ileum - microbiology Ileum - pathology Inflammation Inflammatory bowel disease Inflammatory bowel diseases Internal medicine Intestinal microflora Intestinal Mucosa - metabolism Intestinal Mucosa - microbiology Intestinal Mucosa - pathology Intestine Laboratories Male Mass spectrometry Medicin Medicine Metabolic Networks and Pathways Metabolism Metagenome Metagenomics Microbiota Microbiota (Symbiotic organisms) Proteins Proteome Proteomics Scientific imaging Shotguns Signatures Studies Target recognition Twins, Monozygotic California Belgium United States > US Maryland Tennessee Baltimore Maryland
ISSN:	1932-6203, 1932-6203
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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.
AbstractList	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.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. 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.
Audience	Academic
Author	Pan, Chongle Fraser, Claire M. Darzi, Youssef Mongodin, Emmanuel F. Erickson, Alison R. Lamendella, Regina Jansson, Janet K. Tysk, Curt Halfvarson, Jonas Henrissat, Bernard Cantarel, Brandi L. Verberkmoes, Nathan C. Hettich, Robert L. Shah, Manesh Raes, Jeroen
AuthorAffiliation	2 Graduate School of Genome Science and Technology, University of Tennessee, Knoxville, Tennessee, United States of America 5 Bioinformatics and Eco-Systems Biology lab, Department of Structural Biology, Vrije Universiteit Brussel, Brussels, Belgium 6 Research Group of Microbiology (MICR), Faculty of Sciences and Bioengineering Sciences, Vrije Universiteit Brussel, Brussels, Belgium 8 Architecture et Fonction des Macromolécules Biologiques, UMR6098, Centre national de la recherche scientifique, Universités Aix-Marseille I & II, Marseille, France University of Illinois, United States of America 3 Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, United States of America 4 Department of Ecology, Earth Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America 1 Chemical Science Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee, United States of America 7 Department of Internal Medicine, Divisio
AuthorAffiliation_xml	– name: 7 Department of Internal Medicine, Division of Gastroenterology, Örebro University Hospital and School of Health and Medical Sciences, Örebro University, Örebro, Sweden – name: University of Illinois, United States of America – name: 6 Research Group of Microbiology (MICR), Faculty of Sciences and Bioengineering Sciences, Vrije Universiteit Brussel, Brussels, Belgium – name: 1 Chemical Science Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee, United States of America – name: 8 Architecture et Fonction des Macromolécules Biologiques, UMR6098, Centre national de la recherche scientifique, Universités Aix-Marseille I & II, Marseille, France – name: 3 Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, United States of America – name: 4 Department of Ecology, Earth Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America – name: 2 Graduate School of Genome Science and Technology, University of Tennessee, Knoxville, Tennessee, United States of America – name: 5 Bioinformatics and Eco-Systems Biology lab, Department of Structural Biology, Vrije Universiteit Brussel, Brussels, Belgium
Author_xml	– sequence: 1 givenname: Alison R. surname: Erickson fullname: Erickson, Alison R. – sequence: 2 givenname: Brandi L. surname: Cantarel fullname: Cantarel, Brandi L. – sequence: 3 givenname: Regina surname: Lamendella fullname: Lamendella, Regina – sequence: 4 givenname: Youssef surname: Darzi fullname: Darzi, Youssef – sequence: 5 givenname: Emmanuel F. surname: Mongodin fullname: Mongodin, Emmanuel F. – sequence: 6 givenname: Chongle surname: Pan fullname: Pan, Chongle – sequence: 7 givenname: Manesh surname: Shah fullname: Shah, Manesh – sequence: 8 givenname: Jonas surname: Halfvarson fullname: Halfvarson, Jonas – sequence: 9 givenname: Curt surname: Tysk fullname: Tysk, Curt – sequence: 10 givenname: Bernard surname: Henrissat fullname: Henrissat, Bernard – sequence: 11 givenname: Jeroen surname: Raes fullname: Raes, Jeroen – sequence: 12 givenname: Nathan C. surname: Verberkmoes fullname: Verberkmoes, Nathan C. – sequence: 13 givenname: Claire M. surname: Fraser fullname: Fraser, Claire M. – sequence: 14 givenname: Robert L. surname: Hettich fullname: Hettich, Robert L. – sequence: 15 givenname: Janet K. surname: Jansson fullname: Jansson, Janet K.
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/23209564$$D View this record in MEDLINE/PubMed https://www.osti.gov/biblio/1092312$$D View this record in Osti.gov https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-27418$$DView record from Swedish Publication Index (Örebro universitet)
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CorporateAuthor	Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
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Snippet	Crohn's disease (CD) is an inflammatory bowel disease of complex etiology, although dysbiosis of the gut microbiota has been implicated in chronic...
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SubjectTerms	Acids Acquired immune deficiency syndrome AIDS Bacteria Bacteria - genetics Bacteria - metabolism Bioengineering Bioindicators Bioinformatics Biology Biomarkers Carbohydrate metabolism Carbohydrates Cluster Analysis Colon Crohn Disease - metabolism Crohn Disease - microbiology Crohn's Disease Crohns disease Development and progression Diagnostic systems Dysbacteriosis Earth science Etiology Female Gastroenterology Gastrointestinal diseases Gastrointestinal Tract - metabolism Gastrointestinal Tract - microbiology Genomes Humans Ileum Ileum - metabolism Ileum - microbiology Ileum - pathology Inflammation Inflammatory bowel disease Inflammatory bowel diseases Internal medicine Intestinal microflora Intestinal Mucosa - metabolism Intestinal Mucosa - microbiology Intestinal Mucosa - pathology Intestine Laboratories Male Mass spectrometry Medicin Medicine Metabolic Networks and Pathways Metabolism Metagenome Metagenomics Microbiota Microbiota (Symbiotic organisms) Proteins Proteome Proteomics Scientific imaging Shotguns Signatures Studies Target recognition Twins, Monozygotic
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Title	Integrated Metagenomics/Metaproteomics Reveals Human Host-Microbiota Signatures of Crohn's Disease
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