Document Detail


NOD2-mediated dysbiosis predisposes mice to transmissible colitis and colorectal cancer.
MedLine Citation:
PMID:  23281400     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Instability in the composition of gut bacterial communities (dysbiosis) has been linked to common human intestinal disorders, such as Crohn's disease and colorectal cancer. Here, we show that dysbiosis caused by Nod2 deficiency gives rise to a reversible, communicable risk of colitis and colitis-associated carcinogenesis in mice. Loss of either Nod2 or RIP2 resulted in a proinflammatory microenvironment that enhanced epithelial dysplasia following chemically induced injury. The condition could be improved by treatment with antibiotics or an anti-interleukin-6 receptor-neutralizing antibody. Genotype-dependent disease risk was communicable via maternally transmitted microbiota in both Nod2-deficient and WT hosts. Furthermore, reciprocal microbiota transplantation reduced disease risk in Nod2-deficient mice and led to long-term changes in intestinal microbial communities. Conversely, disease risk was enhanced in WT hosts that were recolonized with dysbiotic fecal microbiota from Nod2-deficient mice. Thus, we demonstrated that licensing of dysbiotic microbiota is a critical component of disease risk. Our results demonstrate that NOD2 has an unexpected role in shaping a protective assembly of gut bacterial communities and suggest that manipulation of dysbiosis is a potential therapeutic approach in the treatment of human intestinal disorders.
Authors:
Aurélie Couturier-Maillard; Thomas Secher; Ateequr Rehman; Sylvain Normand; Adèle De Arcangelis; Robert Haesler; Ludovic Huot; Teddy Grandjean; Aude Bressenot; Anne Delanoye-Crespin; Olivier Gaillot; Stefan Schreiber; Yves Lemoine; Bernhard Ryffel; David Hot; Gabriel Nùñez; Grace Chen; Philip Rosenstiel; Mathias Chamaillard
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-01-02
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  123     ISSN:  1558-8238     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-04-19     Completed Date:  2013-05-13     Revised Date:  2014-05-16    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  700-11     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Colitis / etiology*,  metabolism,  microbiology,  pathology
Colorectal Neoplasms / etiology*,  metabolism,  microbiology,  pathology
Digestive System / metabolism,  microbiology,  pathology
Disease Models, Animal
Female
Humans
Male
Metagenome
Mice
Mice, Knockout
Nod2 Signaling Adaptor Protein / deficiency*,  genetics
Pregnancy
Receptor-Interacting Protein Serine-Threonine Kinases / deficiency,  genetics
Risk Factors
Grant Support
ID/Acronym/Agency:
P30 DK034933/DK/NIDDK NIH HHS; R01 DK061707/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Card15 protein, mouse; 0/Nod2 Signaling Adaptor Protein; EC 2.7.1.-/Ripk2 protein, mouse; EC 2.7.11.1/Receptor-Interacting Protein Serine-Threonine Kinases
Comments/Corrections
Comment In:
Gut Microbes. 2013 Jul-Aug;4(4):353-6   [PMID:  23778641 ]
Cancer Discov. 2013 Mar;3(3):OF17   [PMID:  23475887 ]

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