Autor: |
Jakob Begun, Rabina Giri, Khushi Shamsunnahar, Mark Morrison, Emily C. Hoedt, Páraic Ó Cuív, Robert J. Capon, Michael A. McGuckin |
Jazyk: |
angličtina |
Rok vydání: |
2019 |
Předmět: |
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DOI: |
10.1101/2019.12.16.861872 |
Popis: |
Evidence is emerging that microbiome–immune system crosstalk regulates the tenor of host intestinal immunity and predisposition to inflammatory bowel disease (IBD). We identified five NF-κB suppressive strains affiliated with Clostridium clusters IV, XIVa and XV that independently suppressed secretion of the chemokine IL-8 by peripheral blood mononuclear cells and gut epithelial organoids from healthy human subjects, as well as patients with the predominant IBD subtypes, Crohn’s disease and ulcerative colitis. The NF-κB suppressive Clostridium bolteae AHG0001, but not C. bolteae BAA-613, suppressed cytokine-driven inflammatory responses and endoplasmic reticulum stress in gut epithelial organoids derived from Winnie mice that develop spontaneous colitis. This predicted in vivo responses thereby validating a precision medicine approach to treat Winnie colitis and suggesting the microbiome may function as an extrinsic regulator of host immunity. Finally, we identified a novel molecule associated with NF-κB suppression indicating gut bacteria could be harnessed to develop new therapeutics. |
Databáze: |
OpenAIRE |
Externí odkaz: |
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