The Cheese Matrix Modulates the Immunomodulatory Properties of Propionibacterium freudenreichii CIRM-BIA 129 in Healthy Piglets

Abstract

Propionibacterium freudenreichii is a beneficial bacterium, used as a cheese starter, which presents versatile probiotic properties. These properties are strain-dependent. We hypothesized they may also be delivery vehicle-dependent. In this study, we thus explored in healthy piglets how the cheese matrix affects the immunomodulatory properties of P. freudenreichii. During 2 weeks, three groups of weaned piglets consumed, respectively, P. freudenreichii as a liquid culture (PF-culture), P. freudenreichii under the form of a cheese (PF-cheese), or a control sterile cheese matrix (Cheese-matrix). The in vivo metabolic activity of P. freudenreichii was assessed by determining short chain fatty acids (SCFA) concentration and bifidobacteria population in feces. Whatever the delivery vehicle, P. freudenreichii was metabolically active in piglets’ colon and enhanced both bifidobacteria and SCFA in feces. P. freudenreichii consumption decreased the secretion of TNFα and of IL-10 by peripheral blood mononuclear cells (PBMC). It did not alter IL-10, IFNγ, IL-17, and TNFα secretion in mesenteric lymph node immune cells (MLNC). PF-cheese enhanced significantly Treg phenotype, while PF-culture decreased significantly Th17 phenotype in PBMC and MLNC. Remarkably, only PF-cheese induced an increase of Th2 phenotype in PBMC and MLNC. Ex vivo stimulation of PBMC and MLNC by Lipopolysaccharides and Concanavalin A emphasized the difference in the immunomodulatory responses between PF-culture and PF-cheese group, as well as between PBMC and MLNC. This study shows the importance to consider the delivery vehicle for probiotic administration. It confirms the anti-inflammatory potential of P. freudenreichii. It opens new perspectives for the use propionibacteria-fermented products as preventive agents for inflammatory bowel diseases and intestinal infectious diseases.

Extracellular Vesicles Produced by the Probiotic Propionibacterium freudenreichii CIRM-BIA 129 Mitigate Inflammation by Modulating the NF-κB Pathway

“…The predicted interactions mapped to several immunology-related KEGG terms, such as signal transduction, infectious diseases and the immune system, thus shedding light on a possible immunomodulatory role for P. freudenreichii EVs. These predictions corroborate some previous findings which associated the P. freudenreichii bacterium with immunomodulatory roles ( Foligne et al, 2010 ; Deutsch et al, 2017 ; Do Carmo et al, 2017 ; Frohnmeyer et al, 2018 ; Rabah et al, 2018a ). Interestingly, the predicted data also suggested that this immunomodulation could involve the NF-κB pathway, since the nuclear factor NF-κB p105 subunit (NFKB1, P19838) was the most frequent interacting human protein according to the intersppi predictions and also the interactions shared between the two methods.…”

“…As well as metabolism-related proteins, other proteins packed into EVs are also related to interactions between P. freudenreichii and the host: SlpB (PFCIRM129_00700) and SlpE (PFCIRM129_05460) surface-layer proteins, the BopA solute binding protein (PFCIRM129_08120), internaline A (InlA, PFCIRM129_12235), the hypothetical protein PFCIRM129_10785 and the GroL2 chaperonin (PFCIRM129_10100) ( Le Maréchal et al, 2015 ; Deutsch et al, 2017 ; Do Carmo et al, 2017 ). It has been shown that SlpB mediates the adhesion of P. freudenreichii CIRM-BIA 129 to intestinal epithelial HT29 cells ( Do Carmo et al, 2017 ), reduces LPS-induced IL-8 expression in HT-29 cells ( Do Carmo et al, 2019 ) and participates in the induction of anti-inflammatory cytokines such as IL-10 in human peripheral blood mononuclear cells, mesenteric lymph nodes cells and epithelial HT29 cells ( Foligne et al, 2010 ; Le Maréchal et al, 2015 ; Deutsch et al, 2017 ; Rabah et al, 2018a ). Also, inactivation of the gene encoding SlpE suppresses IL-10 induction by P. freudenreichii CIRM-BIA 129 ( Deutsch et al, 2017 ).…”

“…Propionibacterium freudenreichii has also been regarded consistently as a probiotic species, mainly because of its immunomodulatory properties and protective effects against experimentally induced inflammation in vivo ( Lan et al, 2007a , 2008 ; Foligne et al, 2010 ; Cousin et al, 2012 ; Rabah et al, 2018a ; Do Carmo et al, 2019 ). P. freudenreichii is a Gram-positive, pleiomorphic, microaerophilic dairy bacterium that is generally recognized as safe (GRAS) and has a qualified presumption of safety (QPS) status ( Loux et al, 2015 ; Deutsch et al, 2017 ; Rabah et al, 2017 ).…”

Beneficial Propionibacteria within a Probiotic Emmental Cheese: Impact on Dextran Sodium Sulphate-Induced Colitis in Mice

“…L. delbrueckii subsp. lactis CNRZ327, as well P. freudenreichii CIRM-BIA 129, were previously shown to increase, in animal models, the subset of Treg FOXP3+ cells, which produce a high amount of IL-10 [18,23,47]. Similarly, TGFβ is an anti-inflammatory mediator which is highly produced by mononuclear cells of UC patients [50].…”

“…This anti-inflammatory effect is mediated by specific surface proteins, found only at the surface of specific strains of P. freudenreichii [15,16]. A dairy food matrix was shown to protect such immunomodulatory surface proteins from digestive proteolysis [17,18]. Furthermore, consumption of experimental cheese fermented by P. freudenreichii, alone or with Lactobacillus delbrueckii subsp.…”