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Bacterial infections in the gastrointestinal tract represent a major global health problem, even in the presence of normally effective mucosal immune mechanisms. Milk fermented by Lactobacillus helveticus R389 (FM) or its non-bacterial fraction obtained by milk fermentation at controlled pH 6 (NBF) are able to activate the small intestine mucosal immune response according to previous studies. In this work we aimed at comparing their protection capacity against an infection by Salmonella enteritidis serovar Typhimurium and at studying the mechanisms involved. In a completely randomized design, BALB/c mice received FM or NBF for 2, 5 or 7 consecutive days, followed by a single oral challenge with S. Typhimurium (10(7) cells/mouse). The increase in the number of IgA+ cells in the lamina propria of the small intestine, after the feeding periods, was accompanied by an increase in the luminal content of total S-IgA. However, no antibodies were produced against the NBF. In mice given the FM or the NBF for 7 consecutive days, lower levels of liver colonization on day 7 post-challenge with S. Typhimurium, higher luminal contents of specific anti-Salmonella S-IgA, higher percentages of survival to infection and lower numbers of MIP-1alpha+ cells in the lamina propria were observed. In this work we observed that in both the FM or the NBF there are active principles that confer enhanced protection against S. Typhimurium infection. However, the mechanisms underlying mucosal immunomodulation and protection are different. In those mechanisms, the mucosal immune response would seem to be more involved than the competitive or exclusion mechanisms between L. helveticus R389 and S. enteritidis serovar Typhimurium.

Dietary proteins harbour bioactive peptides that can be released by a fermentation process. Fish proteins are a valuable and little-exploited source of potentially active biopeptides. The aim of this research was to evaluate the effects of a commercially available fermented fish protein concentrate (Seacure) (FPC) derived from a fermentation process, on the mucosal immune response in a murine model. BALB/c mice received the FPC or the non-fermented powder at different concentrations (0.20, 0.25 or 0.30mg/ml) for 2, 5 or 7 consecutive days. At the end of each feeding period, histological studies of the gut were carried out and the phagocytic activity of peritoneal macrophages, the number of IgA+ cells in the small intestine lamina propria and bronchial tissue and the number of IL-4+, IL-6+, IL-10+, IFNgamma+ and TNFalpha+ cells in the small intestine lamina propria were determined. Different accumulative doses of FPC did not induce any inflammatory immune response and the normal morphology of the small intestine was not affected. Phagocytic activity of peritoneal macrophages was enhanced following FPC administration at 0.3mg/ml for 7 consecutive days. The number of IgA+ cells increased in the small intestine lamina propria but not in the bronchial tissue. IL-4, IL-6 and IL-10 were all significantly increased in the lamina propria of the small intestine of animals that received FPC. At the same time, some pro-inflammatory cytokines such as IFNgamma and TNFalpha also increased, but the intestinal homoeostasis was maintained and no tissue damage was observed. We conclude that FPC is an immunomodulating food with a demonstrated capacity to enhance non-specific host defense mechanisms.

Innate immunity that protects against pathogens in the tissues and circulation is the first line of defense in the immune reaction, where macrophages have a critical role in directing the fate of the infection. We recently demonstrated that kefir modulates the immune response in mice, increasing the number of IgA+ cells in the intestinal and bronchial mucosa and the phagocytic activity of peritoneal and pulmonary macrophages. The aim of this study was to further characterize the immunomodulating capacity of the two fractions of kefir (F1: solids including bacteria and F2: liquid supernatant), by studying the cytokines produced by cells from the innate immune system: peritoneal macrophages and the adherent cells from Peyer's patches. BALB/c mice were fed either kefir solid fraction (F1) or kefir supernatant (F2) for 2, 5 or 7 consecutive days. The number of cytokine (IL-1alpha, IFNgamma, TNFalpha, IL-6 and IL-10) producing cells was determined on peritoneal macrophages and adherent cells from Peyer's patches. Both kefir fractions (F1 and F2) induced similar cytokine profiles on peritoneal macrophages (only TNFalpha and IL-6 were up-regulated). All cytokines studied on adherent cells from Peyer's patches were enhanced after F1 and F2 feeding, except for IFNgamma after F2 administration. Moreover, the percentage of IL-10+cells induced by fraction F2 on adherent cells from Peyer's patches was significantly higher than the one induced by fraction F1. Different components of kefir have an in vivo role as oral biotherapeutic substances capable of stimulating immune cells of the innate immune system, to down-regulate the Th2 immune phenotype or to promote cell-mediated immune responses against tumours and also against intracellular pathogenic infections.

Antitumour activity is an effect attributed to probiotics and fermented foods. Here, the immune cells in mammary glands and cytokine concentration in serum were analyzed using mice fed with milk fermented by Lactobacillus helveticus R389 or L89 (proteolytic-deficient variant), injected or not with breast tumour cells. Mice were fed 7 days with fermented milk, injected with breast tumour cells and 4 days post-injection, they received fermented milk. IgA, CD4, CD8, cytokines and Bcl-2 positive cells in mammary glands and cytokine in serum were determined. Mice fed with L. helveticus R389 fermented milk and injected with tumour cells increased IgA and CD4 positive cells in mammary glands (tumour control increased CD8 + cells). Mice from fermented milk control groups (without tumour cell injection) did not show changes in immune cell or cytokine positive cell numbers. IL-10 increases and IL-6 decreases were more pronounced in mice fed with milk fermented by L. helveticus R389 than in the other groups. This study demonstrated the immunoregulatory capacity of milk fermented by L. helveticus R389 on the immune response in mammary glands in presence of a local pathology (breast tumour). Orally administered fermented products could be used to modify the immune cell activation in distant mucosal sites and maintain these cells alert, but local stimulus was necessary to produce the activation of a local immune response in mammary glands, which could modulate the immune-endocrine relationship in these glands.