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Mucosal Immunol. 2019 May;12(3):720-732. doi: 10.1038/s41385-018-0128-y. Epub 2019 Jan 16.

Nod2 influences microbial resilience and susceptibility to colitis following antibiotic exposure.

Author information

1
Department of Immunology, University of Toronto, Toronto, ON, M5S 1A8, Canada.
2
Zane Cohen Centre for Digestive Diseases, The Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, M5T 3L9, Canada.
3
Department of Medicine, University of Toronto, Toronto, ON, M5S 1A8, Canada.
4
St. Michael's Hospital, Toronto, ON, M5B 1W8, Canada.
5
Department of Immunology, University of Toronto, Toronto, ON, M5S 1A8, Canada. ken.croitoru@sinaihealthsystem.ca.
6
Zane Cohen Centre for Digestive Diseases, The Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, M5T 3L9, Canada. ken.croitoru@sinaihealthsystem.ca.
7
Department of Medicine, University of Toronto, Toronto, ON, M5S 1A8, Canada. ken.croitoru@sinaihealthsystem.ca.
8
Division of Gastroenterology, Mount Sinai Hospital, Toronto, ON, M5G 1X5, Canada. ken.croitoru@sinaihealthsystem.ca.

Abstract

Inflammatory bowel disease (IBD) etiology involves genetic susceptibility, environmental triggers, and the gut microbiome. Antibiotic exposure is associated with IBD, both in early life and adulthood. Here, we investigated whether Nod2-deficiency influenced response of the gut microbiota to antibiotics and subsequent colitis susceptibility. Wild-type and Nod2-/- littermate mice were treated with amoxicillin as adults or neonates, and fecal samples were collected for 16S rRNA sequencing. Five weeks after antibiotic exposure, dextran sulfate sodium (DSS) colitis was induced. Antibiotic treatment altered the microbiota of adult WT and Nod2-/- mice, but recovery was delayed in Nod2-/- mice. Neonatal antibiotic treatment significantly changed the microbiota at weaning in WT and Nod2-/- littermates; however, Nod2-/- mice maintained reduced microbial diversity 14 days after cessation of antibiotics. Although treatment of adult mice did not influence susceptibility to colitis, neonatally treated Nod2-/- mice developed a more severe colitis. Moreover, the colitis phenotype was transferable through fecal transplantation into germ-free Nod2-/- recipients, and was associated with changes in intestinal T cells and the cytokine milieu following inflammation. These data demonstrate that neonatal antibiotic exposure has long-lasting influence on the microbiota and mucosal immunity, and may explain how NOD2 contributes to the risk of intestinal inflammation.

PMID:
30651577
DOI:
10.1038/s41385-018-0128-y
[Indexed for MEDLINE]

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