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Bioactives produced by gut bacteria to modulate immune response

Presented by
R. Giri, University of Queensland, Australia
ECCO 2020
An anaerobic culturing and NF-κB reporter assay system allowed for the rapid identification of bacteria producing immunomodulatory bioactives. The investigators think this may lead to the development of novel therapeutics [1].

NF-κB is a protein complex that controls transcription of DNA, cytokine production, and cell survival. In the study, the NF-κB suppressive effects of culture supernatants from 23 different isolates were tested on colonic epithelial cell lines. Suppressive culture supernatants were also tested on human-derived colonic organoids from inflammatory bowel disease (IBD) patients and healthy controls, and IL-8 expression was measured. Furthermore, culture supernatants from one specific NF-κB-suppressive Clostridium strain (AHG0001) was also tested in a spontaneous colitis mouse model in vivo.

Culture supernatants from 5 of 23 screened isolates significantly suppressed NF-κB activation. The selected culture supernatants also suppressed IL-8 secretion in peripheral blood mononuclear cells and gut organoids from both UC and CD patients, as well as healthy controls, with notable individual variation. Culture supernatants from AHG0001 reduced disease activity, improved histologic inflammation, and reduced the pro-inflammatory gene expression in the colitis mouse model. The authors concluded that their in vivo and ex vivo testing using a spontaneous colitis model and patient-derived organoids demonstrates the potential of bacterial-based therapeutics.

    1. Giri R, et al. ECCO-IBD 2020, OP36.

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