Impact of a probiotic fermented milk in the gut ecosystem and in the systemic immunity using a non-severe protein-energy-malnutrition model in mice

Abstract

BackgroundMalnutrition affects the immune response, causing a decrease of defence mechanisms and making the host more susceptible to infections. Probiotics can reconstitute the intestinal mucosa and stimulate local and systemic immunity. The aim of this work was evaluate the effects of a probiotic fermented milk as a complement of a re-nutrition diet, on the recovery of the intestinal barrier, and mucosal and systemic immune functions in a murine model of non-severe protein-energy-malnutrition. Its potential protection against Salmonella enterica serovar Typhimurium (S. Typhimurium) infection was also analyzed.MethodsMice were undernourished and divided into 3 groups according to the dietary supplement received during re-nutrition (milk, probiotic fermented milk or its bacterial free supernatant) and compared to well-nourished and malnourished mice. They were sacrificed previous to the re-nutrition and 5 days post re-nutrition. The phagocytic activity of macrophages from spleen and peritoneum and the changes in the intestinal histology and microbiota were evaluated. Different immune cell populations and cytokine productions were analyzed in the small intestine tissues. The effect of the re-nutrition supplements on the systemic immunity using OVA antigen and against an infection with S. Typhimurium was also studied.ResultsProbiotic fermented milk was the most effective re-nutrition diet that improved the intestinal microbiota. Its administration also increased the number of IgA+ cells, macrophages and dendritic cells. The production of different cytokine (IFN-γ, TNF-α, IL-12) by these cells and the phagocytic activity in peritoneum and spleen was also increased. This re-nutrition diet also stimulated the systemic immune response against OVA antigen which was diminished after the malnutrition period and also improved the host response against S. Typhimurium, decreasing the spread of pathogenic bacteria to the liver and the spleen. The importance of the metabolites released during milk fermentation was also demonstrated through the analysis of the bacterial free supernatant obtained from the probiotic fermented milk, but the whole product showed the best effects in the parameters evaluated in this study.ConclusionsThe administration of probiotic fermented milk as a dietary supplement during the re-nutrition process in a murine immunodeficiency model by malnutrition could be a good adjuvant diet to improve the gut and systemic immune response for the protection against Salmonella infection.

Cross-talk between probiotic lactobacilli and host immune system

“…casei DN‐114‐001 (10 8 CFU ml −1 ) in nonsevere protein‐energy‐malnutrition mice model, all the test groups showed similar values for goblet cells without significant differences compared with both control groups (malnourished and well‐nourished) (Galdeano et al . ). The intestinal villi of malnourished control group were short and their numbers were lower than in the well‐nourished and Lact.…”

“…casei DN‐114‐001 (10 8 CFU ml −1 ), presented the increase in phagocytic activity of macrophages isolated from peritoneum and spleen (Galdeano et al . ).…”

“…casei DN‐114‐001 on translocation of Salmonella typhimurium to spleen, liver and large intestine was prominent in mice and illustrated by a significant decrease in Salmonella counts (Galdeano et al . ). In a similar study, the level of IgA and IgG in serum and S‐IgA was increased only in co‐infection group of the probiotic Lactobacillus sp.…”

“…Although strong pro-inflammatory responses after TLRs stimulation may be beneficial, TLR signalling needs to be fine-tuned to achieve an effective response against dangerous exogenous and endogenous factors, limiting a pathological reaction and restoring the immune balance. Therefore, several mechanisms have evolved which negatively regulate TLR-induced cellular responses at multiple levels of the signalling cascade (Gomariz et al 2010). These mechanisms act at different levels: as extracellular regulators (soluble TLR2 and TLR4), as transmembrane protein regulators (RP105, ST2L, single immunoglobulin interleukin-1-related receptor (SIGGIR), TNF-related apoptosis-inducing ligand receptor (TRAILR)), as negative regulators of adapter molecules (soluble MyD88 (MyD88s), sterile a and heat-armadillo motifs (SARM), suppressor of cytokine signalling 1 (SOCS1)), as factors affecting effector proteins (interleukin-1 receptor-associated kinase M (IRAK-M), IRAK2, TNF receptor-associated factor 4 (TRAF4), toll-interacting protein (TOLLIP), A20, b-arrestins 1 and 2, LIND, FLN29, CYLD, SHIP-2) and finally as molecules affecting transcription factors (Pin-2, phosphatidylinositol 3-kinase (PI3K), ATF-3, Bcl3) (Liew et al 2006).…”

Gut microbiota imbalance and chaperoning system malfunction are central to ulcerative colitis pathogenesis and can be counteracted with specifically designed probiotics: a working hypothesis

“…Thirdly, probiotics stimulate the mucosal immune system in the patient's intestinal tract to secrete protective immunoglobulins (Ig) such as secretory IgA and protective defensins, and they produce bacteriocins into the lumen [82]. It has also been shown that Lactobacillus brevis and Streptococcus thermophilus selectively stimulate apoptosis of mucosal immune cells counteracting the excessive accumulation of these cells in the gut [83].…”