Abstract
Faecalibacterium prausnitzii and its supernatant showed protective effects in different chemically-induced colitis models in mice. Recently, we described 7 peptides found in the F. prausnitzii supernatant, all belonging to a protein called Microbial Anti-inflammatory Molecule (MAM). These peptides were able to inhibit NF-κB pathway in vitro and showed anti-inflammatory properties in vivo in a DiNitroBenzene Sulfate (DNBS)-induced colitis model. In this current proof we tested MAM effect on NF-κB pathway in vivo, using a transgenic model of mice producing luciferase under the control of NF-κB promoter. Moreover, we tested this protein on Dextran Sodium Sulfate (DSS)-induced colitis in mice. To study the effect of MAM we orally administered to the mice a Lactococcus lactis strain carrying a plasmid containing the cDNA of MAM under the control of a eukaryotic promoter. L. lactis delivered plasmids in epithelial cells of the intestinal membrane allowing thus the production of MAM directly by host. We showed that MAM administration inhibits NF-κB pathway in vivo. We confirmed the anti-inflammatory properties of MAM in DNBS-induced colitis but also in DSS model. In DSS model MAM was able to inhibit Th1 and Th17 immune response while in DNBS model MAM reduced Th1, Th2, and Th17 immune response and increased TGFβ production.
Highlights
Intestinal microbiota homeostasis contributes to the protective mechanism of intestinal mucosa against the development of chronic inflammation
Colitis was induced in NF-κB-luciferase mice treated or not with LL-pILMAM or LL-pILEMPTY
At D4, the luminescence was lower in DiNitroBenzene Sulfate (DNBS)- induced colitis mice treated with LL-pILMAM than in LL-pILEMPTY or control mice (PBS)
Summary
Intestinal microbiota homeostasis contributes to the protective mechanism of intestinal mucosa against the development of chronic inflammation. Decreased gut levels of F. prausnitzii can result in reduced capacity of self-defense against inflammatory reactions This protective mechanism may involve the inhibition of proinflammatory cytokines and stimulation of anti-inflammatory cytokines secretion by active molecules (Zhang et al, 2014; Quévrain et al, 2016a). PSA, which can be found at the surface of vesicles secreted by B. fragilis, induce the conversion of CD4 (+) T cells into Foxp (+) Treg cells reducing the intestinal inflammation (Round and Mazmanian, 2017). These findings highlighted that the searching for such bioactive molecules remains challenging scientifically but could open the door to innovative therapeutic strategies
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