Microbial Anti-Inflammatory Molecule (MAM) from Faecalibacterium prausnitzii Shows a Protective Effect on DNBS and DSS-Induced Colitis Model in Mice through Inhibition of NF-κB Pathway

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.

Faecalibacterium prausnitzii‐derived microbial anti‐inflammatory molecule regulates intestinal integrity in diabetes mellitus mice via modulating tight junction protein expression

“…Interestingly, the results indicated that F. prausnitzii supernatant potentially regulates cell‐cell adhesion and the tight junction pathway, which are key to the intestinal barrier integrity. MAM, a newly discovered protein product of F. prausnitzii , shows anti‐inflammatory effects in the intestine in IBD . We questioned whether MAM could act on the intestinal barrier.…”

“…MAM, a newly discovered protein product of F. prausnitzii, shows anti-inflammatory effects in the intestine in IBD. 22,39 We questioned whether MAM could act on the intestinal barrier. Our results suggest that MAM potentially modulates numerous biological processes and signaling pathways of the intestinal epithelium.…”

Intestinal Organoids as a Tool for Inflammatory Bowel Disease Research

“…Tregs are abundant in the intestinal mucosa and are also modulated directly by bacterial antigens. For example, Faecalibacterium prausnitzii and Bacteroides fragilis, both common gut commensals, induced Treg activation and differentiation via the surface proteins, microbial anti-inflammatory molecule (MAM) and polysaccharide A (PSA), respectively (14,15). Both F. prausnitzii and B. fragilis are often missing or present at low abundancy in patients with IBD (16).…”

Epithelial-microbial diplomacy: escalating border tensions drive inflammation in inflammatory bowel disease

“…92,93 In accordance with this, Quévrain et al 94 identified a 15 kDa anti-inflammatory protein was secreted by F. prausnitzii. Subsequently, a study by Breyner et al 95 demonstrated F. prausnitzii secreted peptides termed "microbial anti-inflammatory molecules" can inhibit nuclear factor (NF)-κB promoter activity and interleukin (IL)-6 production, leading to protection from experimental colitis in mice through alteration of T cell immune responses. Interestingly, co-culture studies have demonstrated F. prausnitzii does not enhance barrier function but can induce activation of NF-κB signaling downstream of IL-1β in Caco-2 cells.…”