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| Status |
Public on Jan 02, 2013 |
| Title |
NOD2-dependent licensing of the microbiota predispose to transmissible inflammation and tumorigenesis in the colon. |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
Instability in the composition of gut bacterial communities, referred as dysbiosis, has been associated with important human intestinal disorders such as Crohn’s disease and colorectal cancer. Here, we show that dysbiosis coupled to Nod2 or Rip2 deficiency suffices to cause an increased risk for intestinal inflammation and colitis-associated carcinogenesis in mice. Aggravated epithelial lesions and dysplasia upon chemical-induced injury associated with loss of Nod2 or Rip2 can be prevented by antibiotics or anti-IL6R treatment. Nod2-mediated risk for intestinal inflammation and colitis-associated tumorigenesis is communicable through maternally-transmitted microbiota even to wild-type hosts. Disease progression was identified to drive complex NOD2-dependent changes of the colonic-associated microbiota. Reciprocal microbiota transplantation rescues the vulnerability of Nod2-deficient mice to colonic injury. Altogether, our results unveil an unexpected function for NOD2 in shaping a protective assembly of gut microbial communities, providing a rationale for intentional manipulation of genotype-dependent dysbiosis as a causative therapeutic principle in chronic intestinal inflammation.
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| Overall design |
Analysis used RNA extracted from colonic mucosa of untreated, antibiotics-treated or metronidazole-treated C57Bl/6J and Nod2-deficient mice in CAC model. Direct comparisons were performed as follow: C57Bl/6J untreated mice vs Nod2-deficient untreated mice, C57Bl/6J antibiotics-treated mice vs Nod2-deficient antibiotics-treated mice, C57Bl/6J metronidazole-treated mice vs Nod2-deficient metronidazole-treated mice, C57Bl/6J untreated mice vs C57Bl/6J antibiotics-treated mice, C57Bl/6J untreated mice vs C57Bl/6J metronidazole-treated mice, Nod2-deficient untreated mice vs Nod2-deficient antibiotics-treated mice, Nod2-deficient untreated mice vs Nod2-deficient metronidazole-treated mice. Indirect comparisons with control data were made across multiple arrays with raw data pulled from different channels for data analysis.
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| Contributor(s) |
Couturier A, Chamaillard M, Hot D, Huot L |
| Citation(s) |
23281400, 35917251 |
| |
| Submission date |
Sep 27, 2011 |
| Last update date |
Aug 11, 2022 |
| Contact name |
David Hot |
| E-mail(s) |
[email protected]
|
| Organization name |
Institut Pasteur de Lille
|
| Department |
Center for Infection and Immunity of Lille
|
| Lab |
Transcriptomics and Applied Genomics
|
| Street address |
1 rue du professeur Calmette
|
| City |
Lille |
| ZIP/Postal code |
59000 |
| Country |
France |
| |
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| Platforms (1) |
| GPL7202 |
Agilent-014868 Whole Mouse Genome Microarray 4x44K G4122F (Probe Name version) |
|
| Samples (8)
|
| GSM802413 |
B6_repl1_No_treatment_vs_NOD2_repl1_No_treatment |
| GSM802414 |
B6_repl2_No_treatment_vs_NOD2_repl2_No_treatment |
| GSM802415 |
B6_ATB_treatment_vs_NOD2_ATB_treatment |
| GSM802416 |
B6_Metronidazole_treatment_vs_NOD2_Metronidazole_treatment |
| GSM802417 |
B6_No_treatment_vs_B6_ATB_treatment |
| GSM802418 |
B6_No_treatment_vs_B6_Metronidazole_treatment |
| GSM802419 |
NOD2_No_treatment_vs_NOD2_ATB_treatment |
| GSM802420 |
NOD2_No_treatment_vs_NOD2_Metronidazole_treatment |
|
| Relations |
| BioProject |
PRJNA147907 |
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