Secreted microbial metabolites modulate gut immunity and inflammatory tone

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:
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