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bioRxiv · 10.1101/2019.12.16.861872

Secreted microbial metabolites modulate gut immunity and inflammatory tone

Giri, R.·Hoedt, E. C.·Shamsunnahar, K.·McGuckin, M. A.·Morrison, M.·Capon, R. J.·Begun, J.·Cuiv, P. O.
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Abstract

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-{kappa}B 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, Crohns disease and ulcerative colitis. The NF-{kappa}B 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-{kappa}B suppression indicating gut bacteria could be harnessed to develop new therapeutics.

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Giri, R., Hoedt, E. C., Shamsunnahar, K., McGuckin, M. A., Morrison, M., Capon, R. J., Begun, J., Cuiv, P. O.. 2019-12-16. Secreted microbial metabolites modulate gut immunity and inflammatory tone. https://doi.org/10.1101/2019.12.16.861872

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