NOD2 Influences Trajectories of Intestinal Microbiota Recovery After Antibiotic PerturbationSummary
| Autor: | Simone Lipinski, Jacqueline Moltzau Anderson, Konrad Aden, Felix Sommer, John F. Baines, Wei-Hung Pan, Olivier Boulard, Robert Häsler, Sven Künzel, Philip Rosenstiel, Stephanie T. Stengel, Richa Bharti, Maren Falk-Paulsen, Ateequr Rehman, Mathias Chamaillard |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
medicine.drug_class Antibiotics IBD Nod2 Signaling Adaptor Protein PCoA principle coordinate analysis Gut flora Inflammatory bowel disease SPF specific pathogen free Bacterial cell structure NOD2 Microbiology 03 medical and health sciences 0302 clinical medicine GEE generalized estimating equation CXCL1 chemokine (C-X-C motif) ligand 1 Gene expression CD Crohn’s disease OTU operational taxonomic unit medicine lcsh:RC799-869 qPCR quantitative real-time polymerase chain reaction Feces Original Research KO knockout IBD inflammatory bowel disease Hepatology biology Microbiota Gastroenterology biology.organism_classification medicine.disease WT wild-type digestive system diseases Anti-Bacterial Agents Gastrointestinal Microbiome rRNA ribosomal RNA GF germ-free NOD2 nucleotide-binding oligomerization domain-containing protein 2 030104 developmental biology ITS internal transcribed spacer Microbial Resilience 030211 gastroenterology & hepatology lcsh:Diseases of the digestive system. Gastroenterology Bacteria Antibiotic Treatment |
| Zdroj: | Cellular and Molecular Gastroenterology and Hepatology, Vol 10, Iss 2, Pp 365-389 (2020) Cellular and Molecular Gastroenterology and Hepatology |
| Popis: | Background & Aims Loss-of-function variants in nucleotide-binding oligomerization domain-containing protein 2 (NOD2) impair the recognition of the bacterial cell wall component muramyl-dipeptide and are associated with an increased risk for developing Crohn’s disease. Likewise, exposure to antibiotics increases the individual risk for developing inflammatory bowel disease. Here, we studied the long-term impact of NOD2 on the ability of the gut bacterial and fungal microbiota to recover after antibiotic treatment. Methods Two cohorts of 20-week-old and 52-week-old wild-type (WT) C57BL/6J and NOD2 knockout (Nod2-KO) mice were treated with broad-spectrum antibiotics and fecal samples were collected to investigate temporal dynamics of the intestinal microbiota (bacteria and fungi) using 16S ribosomal RNA and internal transcribed spacer 1 sequencing. In addition, 2 sets of germ-free WT mice were colonized with either WT or Nod2-KO after antibiotic donor microbiota and the severity of intestinal inflammation was monitored in the colonized mice. Results Antibiotic exposure caused long-term shifts in the bacterial and fungal community composition. Genetic ablation of NOD2 was associated with delayed body weight gain after antibiotic treatment and an impaired recovery of the bacterial gut microbiota. Transfer of the postantibiotic fecal microbiota of Nod2-KO mice induced an intestinal inflammatory response in the colons of germ-free recipient mice compared with respective microbiota from WT controls based on histopathology and gene expression analyses. Conclusions Our data show that the bacterial sensor NOD2 contributes to intestinal microbial community composition after antibiotic treatment and may add to the explanation of how defects in the NOD2 signaling pathway are involved in the etiology of Crohn’s disease. Graphical abstract |
| Databáze: | OpenAIRE |
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