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. This current paper 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 Th1and Th17 immune response while in DNBS model MAM reduced Th1, Th2 and Th17 immune response and increased TGFβ production.

Metabolic disorders are an increasing concern in the industrialized world. Current research has shown a direct link between the composition of the gut microbiota and the pathogenesis of obesity and diabetes. In only a few weeks, an obesity-inducing diet can lead to increased gut permeability and microbial dysbiosis, which contributes to chronic inflammation in the gut and adipose tissues, and to the development of insulin resistance. In this review, we examine the interplay between gut inflammation, insulin resistance, and the gut microbiota, and discuss how some probiotic species can be used to modulate gut homeostasis. We focus primarily on Faecalibacterium prausnitzii, a highly abundant butyrate-producing bacterium that has been proposed both as a biomarker for the development of different gut pathologies and as a potential treatment due to its production of anti-inflammatory metabolites.

Abundance of Faecalibacterium prausnitzii , a dominant bacterium of the human microbiota that exhibits antiinflammatory effects, is decreased in patients with inflammatory bowel diseases (IBD). In humans, colonic lamina propria contains IL-10–secreting, Foxp3 ^– Tregs characterized by a double expression of CD4 and CD8α (DP8α) and a specificity for F. prausnitzii . This Treg subset is decreased in IBD. The in vivo effect of DP8α cells has not been evaluated yet to our knowledge. Here, using a humanized model of a NSG immunodeficient mouse strain that expresses the HLA D–related allele HLA-DR*0401 but not murine class II (NSG-Ab° DR4) molecules, we demonstrated a protective effect of a HLA-DR*0401–restricted DP8α Treg clone combined with F. prausnitzii administration in a colitis model. In a cohort of patients with IBD, we showed an independent association between the frequency of circulating DP8α cells and disease activity. Finally, we pointed out a positive correlation between F. prausnitzii –specific DP8α Tregs and the amount of F. prausnitzii in fecal microbiota in healthy individuals and patients with ileal Crohn’s disease.

B-type oligomeric procyanidins in apples constitute an important source of polyphenols in the human diet. Their role in health is not known, although it is suggested that they generate beneficial bioactive compounds upon metabolization by the gut microbiota. During apple processing, procyanidins interact with cell-wall polysaccharides and form stable complexes. These interactions need to be taken into consideration in order to better assess the biological effects of fruit constituents. Our objectives were to evaluate the impact of these interactions on the microbial metabolization of cell walls and procyanidins, and to investigate the potential anti-inflammatory activity of the resulting metabolome, in addition to analyzing the taxonomical changes which the microbiota undergo. In vitro fermentation of three model apple matrices with microbiota from 4 healthy donors showed that the binding of procyanidins to cell-wall polysaccharides, whether covalently or non-covalently, substantially reduced procyanidin degradation. Although cell wall-unbound procyanidins negatively affected carbohydrate fermentation, they generated more hydroxyphenylvaleric acid than bound procyanidins, and increased the abundance of Adlercreutzia and Gordonibacter genera. The best results in terms of production of anti-inflammatory bioactive metabolites were observed from the apple matrix with no bonds between procyanidins and cell wall polysaccharides, although the matrix with non-covalent bonds was not far behind.

The commensal bacterium Faecalibacterium prausnitzii has unique anti-inflammatory properties, at least some of which have been attributed to its production of MAM, the Microbial Anti-inflammatory Molecule. Previous phylogenetic studies of F. prausnitzii strains have revealed the existence of various phylogroups. In this work, we address the question of whether MAMs from different phylogroups display distinct anti-inflammatory properties. We first performed wide-scale identification, classification, and phylogenetic analysis of MAM-like proteins encoded in different genomes of F. prausnitzii. When combined with a gene context analysis, this approach distinguished at least 10 distinct clusters of MAMs, providing evidence for functional diversity within this protein. We then selected 11 MAMs from various clusters and evaluated their anti-inflammatory capacities in vitro. A wide range of anti-inflammatory activity was detected. MAM from the M21/2 strain had the highest inhibitory effect (96% inhibition), while MAM from reference strain A2-165 demonstrated only 56% inhibition, and MAM from strain CNCM4541 was almost inactive. These results were confirmed in vivo in murine models of acute and chronic colitis. This study provides insights into the family of MAM proteins and generates clues regarding the choice of F. prausnitzii strains as probiotics for use in targeting chronic inflammatory diseases.

Every year, millions of people around the world benefit from radiation therapy to treat cancers localized in the pelvic area. Damage to healthy tissue in the radiation field can cause undesirable toxic effects leading to gastrointestinal complications called pelvic radiation disease. A change in the composition and/or function of the microbiota could contribute to radiation-induced gastrointestinal toxicity. In this study, we tested the prophylactic effect of a new generation of probiotic like Faecalibacterium prausnitzii (F. prausnitzii) on acute radiation-induced colonic lesions. Experiments were carried out in a preclinical model of pelvic radiation disease. Rats were locally irradiated at 29 Gray in the colon resulting in colonic epithelial barrier rupture. Three days before the irradiation and up to 3 d after the irradiation, the F. prausnitzii A2-165 strain was administered daily (intragastrically) to test its putative protective effects. Results showed that prophylactic F. prausnitzii treatment limits radiation-induced para-cellular hyperpermeability, as well as the infiltration of neutrophils (MPO+ cells) in the colonic mucosa. Moreover, F. prausnitzii treatment reduced the severity of the morphological change of crypts, but also preserved the pool of Sox-9+ stem/progenitor cells, the proliferating epithelial PCNA+ crypt cells and the Dclk1+/IL-25+ differentiated epithelial tuft cells. The benefit of F. prausnitzii was associated with increased production of IL-18 by colonic crypt epithelial cells. Thus, F. prausnitzii treatment protected the epithelial colonic barrier from colorectal irradiation. New-generation probiotics may be promising prophylactic treatments to reduce acute side effects in patients treated with radiation therapy and may improve their quality of life.