Evaluation of oral supplementation of free and nanoencapsulated Minthostachys verticillata essential oil on immunological, biochemical and antioxidants parameters and gut microbiota in weaned piglets.

Early weaning is an important stressor that impairs the piglet´s health, and essential oils appear as promising candidates to improve it instead of antibiotics. The aim of this study was to evaluate the effect of oral supplementation of free and nanoencapsulated Minthostachys verticillata essential oil (EO and NEO, respectively) on immunological, biochemical and antioxidants parameters as well as on gut microbiota in weaned piglets. EO was extracted by hydrodistillation and nanoencapsulation was performed by high-energy method using Tween 80 and Span 60 as surfactants. EO and NEO were chemically analyzed by gas chromatography-mass spectrometry (GC-MS). The cytotoxic effects of both EO and NEO was evaluated on Caco-2 cell line. For in vivo assay, male weaned piglets (age: 28 days, mean initial body weight: 11.63 ± 0.37 kg) were randomly distributed in six groups of six animals each (n = 6) and received orally EO (10.0 mg/kg/day) or NEO (2.5, 5.0 and 10.0 mg/kg/day), named hereinafter as EO-10, NEO-2.5, NEO-5 and NEO-10, for 30 consecutive days. Animals not treated or treated with surfactants mixture were evaluated as control and vehicle control. Subsequently, histological, hematological and biochemical parameters, cytokines production, oxidative markers, CD4+/CD8+ T cells and gut microbiota were evaluated. GC-MS analysis was similar in both EO and NEO. The NEO was more toxic on Caco-2 cells than EO. Oral supplementation of EO-10 or NEO-10 improved growth performance compared to control group NEO-2.5 or NEO-5 (p < 0.05) groups. NEO-2.5, NEO-5 and NEO-10 did not alter the morpho-physiology of digestive organs and decreased malondialdehyde (MDA) levels in liver compared to control (p < 0.05) or EO-10 groups (p < 0.05, p < 0.01). In addition, NEO-10 showed an increase in CD4+/CD8+ T cells ratio (p < 0.001), and induced the highest serum levels of IL-10 (p < 0.01). Serum triglycerides levels were significantly lower in animals treated with EO-10 or NEO-2.5, NEO-5 and NEO-10 compared to control group (p < 0.001). Gut microbiota analysis showed that NEO-10 favor the development of beneficial intestinal microorganisms to improve parameters related to early weaning of piglets. In conclusion, EO and NEO improved parameters altered by early weaning in piglets however, NEO was safer and powerful. Therefore, NEO should be further studied to be applied in swine health.

Inorganic phosphate modifies stationary phase fitness and metabolic pathways in Lactiplantibacillus paraplantarum CRL 1905.

Inorganic phosphate (Pi) concentration modulates polyphosphate (polyP) levels in diverse bacteria, affecting their physiology and survival. Lactiplantibacillus paraplantarum CRL 1905 is a lactic acid bacterium isolated from quinoa sourdough with biotechnological potential as starter, for initiating fermentation processes in food, and as antimicrobial-producing organism. The aim of this work was to evaluate the influence of the environmental Pi concentration on different physiological and molecular aspects of the CRL 1905 strain. Cells grown in a chemically defined medium containing high Pi (CDM + P) maintained elevated polyP levels up to late stationary phase and showed an enhanced bacterial survival and tolerance to oxidative stress. In Pi sufficiency condition (CDM-P), cells were ~ 25% longer than those grown in CDM + P, presented membrane vesicles and a ~ 3-fold higher capacity to form biofilm. Proteomic analysis indicated that proteins involved in the "carbohydrate transport and metabolism" and "energy production and conversion" categories were up-regulated in high Pi stationary phase cells, implying an active metabolism in this condition. On the other hand, stress-related chaperones and enzymes involved in cell surface modification were up-regulated in the CDM-P medium. Our results provide new insights to understand the CRL 1905 adaptations in response to differential Pi conditions. The adjustment of environmental Pi concentration constitutes a simple strategy to improve the cellular fitness of L. paraplantarum CRL 1905, which would benefit its potential as a microbial cell factory.

Neuroprotective effects associated with immune modulation by selected lactic acid bacteria in a Parkinson's disease model.

OBJECTIVES: Parkinson's disease (PD) is a neurodegenerative process that affects the motor function and involves an inflammatory response and B vitamin deficiencies. The aim of this study was to evaluate the effect of B-group vitamin-producing and immunomodulatory lactic acid bacteria (LAB) in a murine model of PD. METHODS: The effect of Lactobacillus plantarum CRL 2130 (a riboflavin producer), Streptococcus thermophilus CRL 807 (an immunomodulatory strain), and Streptococcus thermophilus CRL 808 (a folate producer) were evaluated individually and as a mixture in mice injected with 1-methyl-4-fenil-1,2,3,6-tetrahidropiridina. Motor capacity, tyrosine hydrolase in the brain, and cytokine concentrations in serum and brain tissues were evaluated in 1-methyl-4-fenil-1,2,3,6-tetrahidropiridina-treated mice after bacterial supplementation. RESULTS: The mice receiving the selected LAB showed significantly improved motor skills compared with those that did not receive bacterial supplementation. When given the mixture of all 3 strains together, the animals had higher brain tyrosine hydrolase-positive cell counts, decreased inflammatory cytokines interleukin 6 and tumor necrosis factor alpha in serum, and increased antiinflammatory cytokine interleukin 10 in serum and brain tissues compared with animals that did not receive LAB supplementation. CONCLUSIONS: The results showed the potential of a selected LAB mixture to improve motor behavior and neuroinflammation in PD. This probiotic mixture could be used as an adjunct treatment in the control of PD.

Retraction Note to: Lactobacillus casei BL23 regulates Treg and Th17 T-cell populations and reduces DMH-associated colorectal cancer.

This article has been retracted. Please see the retraction notice for more detail: https://doi.org/10.1007/s00535-015-1158-9 .

Application of vitamin-producing lactic acid bacteria to treat intestinal inflammatory diseases.

Recent studies have shown that inflammatory diseases are becoming more frequent throughout the world. The causes of these disorders are multifactorial and include genetic, immunological, and environmental factors, and intestinal microbiota dysbiosis. The use of beneficial microorganisms has shown to be useful in the prevention and treatment of disorders such as colitis, mucositis, and even colon cancer by their immune-stimulating properties. It has also been shown that certain vitamins, especially riboflavin and folate derivatives, have proven to be helpful in the treatment of these diseases. The application of vitamin-producing lactic acid bacteria, especially strains that produce folate and riboflavin together with immune-stimulating strains, could be used as adjunct treatments in patients suffering from a wide range of inflammatory diseases since they could improve treatment efficiency and prevent undesirable side effects in addition to their nutrition values. In this review, the most up to date information on the current knowledge and uses of vitamin-producing lactic acid bacteria is discussed in order to stimulate further studies in this field.

Beneficial effect of a mixture of vitamin-producing and immune-modulating lactic acid bacteria as adjuvant for therapy in a recurrent mouse colitis model.

Inflammatory bowel diseases are chronic and relapsing-remitting disorders that affect the gastrointestinal tract. Previously, the administration of folate and riboflavin-producing lactic acid bacteria (LAB) or an immune-modulating strain showed beneficial effects as they were able to reduce the acute inflammation in mouse models. The aim of this work was to evaluate a mixture of vitamin-producing and immune-modulating LAB administering together with an anti-inflammatory drug during the remission period of a mouse model of recurrent colitis. BALB/c mice were intrarectally instilled with trinitrobenzene sulfonic acid (TNBS) and those who recovered from this acute challenge were given the LAB mixture, mesalazine, or the combination of both (mesalazine + LAB) during 21 days, followed by a second challenge with TNBS. Control mice instilled with ethanol (vehicle of TNBS) and receiving the different treatments were also evaluated in order to study the effect of chronic anti-inflammatory therapy. The combination of mesalazine and LAB mixture was the most effective to decrease the intestinal damage at macroscopic and histological levels and to reduce pro-inflammatory cytokines (IL-6 and TNF-α) in intestinal fluids. In animals instilled with ethanol, mesalazine produced a loss of body weight and intestinal damages with increased IL-6. These side effects were prevented by the co-administration of mesalazine and the LAB mixture. The LAB blend did not affect the primary anti-inflammatory treatment, was able to improve it, and also prevented the side effects of this therapy.

Protective effect of the riboflavin-overproducing strain Lactobacillus plantarum CRL2130 on intestinal mucositis in mice.

OBJECTIVES: Intestinal mucositis (IM) is a local inflammatory response that causes alterations of the intestinal structure that in turn affect nutrient absorption and a side effect that is commonly associated with cancer treatments. Lactobacillus plantarum CRL2130 is a riboflavin-overproducing strain that has previously been shown to provide antiinflammatory properties. The objective of this study was to evaluate the effects of this riboflavin-producing strain in a chemically induced murine mucositis model. METHODS: Mucositis was induced by daily injections of 5-fluororacil (5-FU) after which mice were either given L. plantarum CRL2130, CRL725 (strain from which CRL2130 was derived that does not overproduce riboflavin), or commercial riboflavin twice daily during 6 d of chemotherapy agent injections. The effect of the strains and riboflavin was also evaluated in vitro using Caco-2 intestinal cancer cell cultures to determine if they interfere with 5-FU's anticancer activity. RESULTS: The administration of L. plantarum CRL2130 significantly attenuated the pathologic changes induced by 5-FU in mice such as body weight loss, diarrhea, shortening of villus height, increases in proinflammatory cytokine concentrations, and elevated production of interleukin 10. In vitro assays using Caco-2 cells showed that the effectiveness of 5-FU was not affected by L. plantarum CRL2130 and that this strain exerted an inhibitory mechanism against oxidative stress. CONCLUSIONS: These results indicate that the riboflavin-overproducing strain L. plantarum CRL2130 could be useful to prevent mucositis during cancer treatments and would not affect the primary treatment.

Vitamin Producing Lactic Acid Bacteria as Complementary Treatments for Intestinal Inflammation.

BACKGROUND: Current therapies for against inflammatory bowel disease (IBD) are sometimes limited by high costs, high toxicities and/or undesirable side effects, reasons for which new treatments are constantly being developed and studied. In this regards, an increasing mass of data has demonstrated that fecal transplantations and probiotic supplementations have shown promising effects and could be considered as adjunct IBD treatments to decrease some of the unwanted side effects caused by primary treatments. Furthermore, there is also mounting evidence that suggests that certain vitamins could provide antiinflammatory effects and it has been shown that certain strains of lactic acid bacteria (LAB), the most commonly used probiotic microorganisms, can produce biologically active forms of certain vitamins. OBJECTIVE: To discuss the potential role of the vitamin-producing LAB on intestinal inflammatory diseases. METHOD: A thorough search of bibliographic databases for peer-reviewed research on the effect of vitamins produced by LAB on inflammatory processes was performed. RESULTS: There is mounting research that vitamin producing LAB could provide antiinflammatory effects. CONCLUSION: The potential role of vitamin producing LAB was discussed not only because they could be used to decrease inflammation but also because they could provide the host with essential nutrients that are normally deficient in IBD patients due to altered intestinal morphologies.

Anti-cancer effect of lactic acid bacteria expressing antioxidant enzymes or IL-10 in a colorectal cancer mouse model.

The association between inflammatory bowel diseases and colorectal cancer is well documented. The genetic modification of lactic acid bacteria as a tool to increase the anti-inflammatory potential of these microorganisms has also been demonstrated. Thus the aim of the present work was to evaluate the anti-cancer potential of different genetically modified lactic acid bacteria (GM-LAB) producing antioxidant enzymes (catalase or superoxide dismutase) or the anti-inflammatory cytokine IL-10 (protein or DNA delivery) using a chemical induced colon cancer murine model. Dimethilhydrazine was used to induce colorectal cancer in mice. The animals received GM-LAB producing anti-oxidant enzymes, IL-10 or a mixture of different GM-LAB. Intestinal damage, enzyme activities and cytokines were evaluated and compared to the results obtained from mice that received the wild type strains from which derived the GM-LAB. All the GM-LAB assayed showed beneficial effects against colon cancer even though they exerted different mechanisms of action. The importance to select LAB with innate beneficial properties as the progenitor strain was demonstrated with the GM-LAB producing anti-oxidant enzymes. In addition, the best effects for the mixtures GM-LAB that combine different anti-inflammatory mechanism. Results indicate that mixtures of selected LAB and GM-LAB could be used as an adjunct treatment to decrease the inflammatory harmful environment associated to colorectal cancer, especially for patients with chronic intestinal inflammation who have an increased risk to develop colorectal cancer.

Lactobacillus casei BL23 regulates Treg and Th17 T-cell populations and reduces DMH-associated colorectal cancer.

BACKGROUND: Chronic intestinal inflammation alters host physiology and could lead to colorectal cancer (CRC). We have previously reported beneficial effects of the probiotic strain of Lactobacillus casei BL23 in different murine models of intestinal inflammation. In addition, there is an emerging interest on the potential beneficial effects of probiotics to treat CRC. We thus explored whether L. casei BL23 displays protective effects on CRC. METHODS: Mice were subcutaneously injected with 1,2-dimethylhydrazine (DMH) weekly during 10 weeks and orally administered with L. casei BL23 in the drinking water until the 10th week. Multiple plaque lesions in the large intestine were observed macroscopically and counted and intestinal tissues were also histologically analyzed. Finally, T-cell populations and cytokine production were evaluated after co-incubation of L. casei BL23 with spleen cells from non-treated mice to determine the immuno-modulatory effects of this bacterium. RESULTS: Our results show that oral treatment with this probiotic bacterium modulates host immune responses and significantly protect mice against DMH-induced CRC. This protection may be associated with the modulation of regulatory T-cells towards a Th17-biased immune response accompanied by the expression of regulatory cytokines (IL-6, IL-17, IL-10 and TGF-ß), as demonstrated in L. casei BL23-treated splenocytes, but also with the colonic expression of IL-22 observed in vivo on L. casei BL23-treated mice; suggesting the induction of a fine-tune Th17-biased response. CONCLUSIONS: Altogether our results reveal the high potential of L. casei BL23 to treat CRC and opens new frontiers for the study of immunomodulatory functions of probiotics.

Las leches fermentadas potencialmente probióticas frente a la inflamación intestinal y el cáncer / Potential of probiotic fermented milks in intestinal inflammation and cancer

Mediante modelos con animales se demostró que el consumo de leches fermentadas con microorganismos potencialmente probióticos puede modular la respuesta inmunitaria del hospedador, manteniéndolo en estado de vigilancia, lo que le ayudaría a enfrentar enfermedades como la inflamación intestinal y algunos tipos de cáncer, mejorando su calidad de vida...

Lactobacillus casei CRL 431 administration decreases inflammatory cytokines in a diet-induced obese mouse model.

OBJECTIVES: Obesity is a chronic disease associated with an inflammatory process in which cytokines play an important role. Probiotic microorganisms have been associated with modulation of the host immune system. The aim of this study was to evaluate the influence of the probiotic bacterium Lactobacillus casei CRL 431 on the cytokine response in a model of mice under high-fat diet (HFD) conditions. METHODS: BALB/c mice received a conventional balanced diet or an HFD. The test groups received milk, milk fermented by L. casei (FM), or L. casei as suspension in the drinking water. Proinflammatory and regulatory cytokine producer cells were evaluated in the small intestine and liver; the cytokine levels in the intestinal fluids were also evaluated. The percentages of immune cells as macrophages (F4/80), NKT, CD4+, CD8+ populations were determined in the liver. Adipocytes were also isolated and cultured to evaluate cytokines and the chemokine monocyte chemoattractant protein (MCP)-1 produced by them. RESULTS: The administration of probiotic L. casei CRL 431 exerted an anti-inflammatory response in mice fed an HFD, evidenced mainly by decreasing proinflammatory cytokines, such as interleukin (IL)-6, IL-17, and tumor necrosis factor-α. Probiotic administration also was associated with fewer immune-infiltrating cells in the liver of mice that received the HFD and decreased secretion of MCP-1 by the adipocytes. This last observation could be associated with less macrophage accumulation in the adipose tissues, which is characteristic in the obese host and contributes to maintaining the inflammatory response in this organ. The results obtained show an anti-inflammatory effect of L. casei CRL 431 when it is administered as a supplement of the HFD in a mouse model.

Inhibition of Growth and Metastasis of Breast Cancer in Mice by Milk Fermented With Lactobacillus casei CRL 431.

Breast cancer is the second cause of death in women, who are especially related to uncontrolled metastasis. It was previously demonstrated that the administration of milk fermented by Lactobacillus casei CRL 431 [fermented milk (FM)] delayed the tumor growth in a murine breast cancer model. In this work we evaluated if the administration of FM to mice, starting when the tumor was measurable, can affect not only the tumor growth, but also the extravasation of tumor cells and the lung metastasis. The evaluation of immune cells-infiltrating tumors and lungs was also performed. Tumor volume was calculated. Whole blood, lungs, and liver were processed to count the number of colonies formed by tumor cells. Blood serum was obtained for monocyte chemoattractant protein-1, interleukin (IL)-10, and IL-6 determination, lung tissues for histologic observations, and tumor tissues for angiogenesis determination. Mice that received FM were compared with animals given milk or to the controls without any especial supplementation. The results showed that FM administration to mice decreased or suppressed tumor growth, with less tumor vascularity, extravasation of tumor cells, and lung metastasis. These benefits were associated to modulation of the immune response by decreasing the infiltration of macrophages in both the tumor and the lungs. FM administration maintained an increased antitumor response associated to CD8 lymphocytes, and also increased CD4 lymphocytes that can be involved in the modulation of the immune response. The future evaluation of cytokine profiles will allow knowing more about subpopulation of macrophages and lymphocytes associated to the beneficial effect of this probiotic in the breast cancer model.

Role of probiotics and functional foods in health: gut immune stimulation by two probiotic strains and a potential probiotic yoghurt.

There are numerous reports that show the benefits on the health attributed to the probiotic consumptions. Most of the studies were performed using animal models and only some of them were validated in controlled human trials. The present review is divided in two sections. In the first section we describe how the probiotic microorganisms can interact with the intestinal epithelial cells that are the first line of cell in the mucosal site, focusing in the studies of two probiotic strains: Lactobacillus casei DN-114001 (actually Lactobacillus paracasei CNCMI-1518) and Lactobacillus casei CRL 431. Then we describe same beneficial effects attributed to probiotic administration and the administration of fermented milks containing these microorganisms or potential probiotic yoghurt, principally on the immune system and on the intestinal barrier in different experimental mouse models like enteropathogenic infection, malnutrition, cancer and intestinal inflammation.

Effect of probiotic administration on the intestinal microbiota, current knowledge and potential applications.

Although it is now known that the human body is colonized by a wide variety of microbial populations in different parts (such as the mouth, pharynx and respiratory system, the skin, the gastro- and urogenital tracts), many effects of the complex interactions between the human host and microbial symbionts are still not completely understood. The dysbiosis of the gastrointestinal tract microbiota is considered to be one of the most important contributing factors in the development of many gastrointestinal diseases such as inflammatory bowel disease, irritable bowel syndrome and colorectal cancer, as well as systemic diseases like obesity, diabetes, atherosclerosis and non-alcoholic fatty liver disease. Fecal microbial transplantations appear to be promising therapies for dysbiosis-associated diseases; however, probiotic microorganisms have been growing in popularity due to increasing numbers of studies proving that certain strains present health promoting properties, among them the beneficial balance of the intestinal microbiota. Inflammatory bowel diseases and obesity are the pathologies in which there are more studies showing this beneficial association using animal models and even in human clinical trials. In this review, the association of the human gut microbiota and human health will be discussed along with the benefits that probiotics can confer on this symbiotic activity and on the prevention or treatment of associated diseases.

Correlation between fibronectin binding protein A expression level at the surface of recombinant lactococcus lactis and plasmid transfer in vitro and in vivo.

BACKGROUND: Fibronectin Binding Protein A (FnBPA) is an invasin from Staphylococcus aureus that allows this pathogen to internalize into eukaryote cells. It was previously demonstrated that recombinant Lactococcus lactis expressing FnBPA were invasive and able to transfer a plasmid to eukaryotic cells in vitro and in vivo. In this study, the invasivity of recombinant strains of Lactococcus lactis that express FnBPA under the control of its constitutive promoter or driven by the strong nisin inducible expression system (NICE) were studied. RESULTS: It was demonstrated that the nisA promoter allows an increase of FnBPA expression on the surface of Lactococcus lactis surface, as shown by flow cytometry, which subsequently enhanced internalization and plasmid transfer properties in vitro in Caco2 cells and Bone Marrow Dendritic Cells. In vivo, the use of nisA promoter increase the plasmid transfer in cells of both the small and large intestine of mice. CONCLUSION: FnBPA expression at the surface of recombinant L. lactis is positively correlated to internalization and DNA transfer properties. The recombinant strains of L. lactis that expresses FnBPA under the control of the nisin inducible expression system could thus be considered as an improved tool in the field of DNA transfer.

Modification in the diet can induce beneficial effects against breast cancer.

The population tends to consume foods that in addition to their nutritional values can offer some benefits to their health. There are many epidemiological evidences and research studies in animal models suggesting that diet plays an important role in breast cancer prevention or progression. This review summarized some of the relevant researches about nutrition and cancer during the last years, especially in breast cancer. The analysis of probiotics and fermented products containing lactic acid bacteria in cancer prevention and/or treatment was especially discussed. It was observed that a balance of fatty acids similar to those of traditional Mediterranean diet, the consumption of fruits and vegetables, dietary fiber intake, vitamin supplementation are, along with the intake of probiotic products, the most extensively studied by the negative association to breast cancer risk. The consumption of probiotics and fermented products containing lactic acid bacteria was associated to reduce breast cancer risk in some epidemiological studies. The use of animal models showed the modulation of the host's immune response as one of the important effects associated to the benefices observed with most probiotics. However; future assays in human are very important before the medical community can accept the addition of probiotic or fermented milks containing lactic acid bacteria as supplements for cancer patients.

The administration of milk fermented by the probiotic Lactobacillus casei CRL 431 exerts an immunomodulatory effect against a breast tumour in a mouse model.

Antitumour activity is one of the health-promoting effects attributed to probiotics specially analysed from preclinical models, mostly murine. Here, the effect of milk fermented by the probiotic bacterium Lactobacillus casei CRL 431, on a murine breast cancer model was analysed. Mice were fed with milk fermented by Lactobacillus casei or unfermented milk before and after tumour injection. Rate of tumour development, cytokines in serum, IgA, CD4, CD8, F4/80 and cytokines positive cells in mammary glands were determined. Microvasculature in the tumour tissues was monitored. The effect of fermented milk administration after tumour injection was also evaluated. It was observed that probiotic administration delayed or blocked tumour development. This effect was associated to modulation of the immune response triggered by the tumour. The area occupied by blood vessels decreased in the tumours from mice given fermented milk which agrees with their small tumours, and fewer side effects. Finally, it was observed that probiotic administration after tumour detection was also beneficial to delay the tumour growth. In conclusion, we showed in this study the potential of milk fermented by the probiotic Lactobacillus casei CRL431 to stimulate the immune response against this breast tumour, avoiding or delaying its growth when it was preventively administrated and also when the administration started after tumour cells injection.

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.

BACKGROUND: Malnutrition 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. METHODS: Mice 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. RESULTS: Probiotic 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. CONCLUSIONS: The 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.

Evaluation of the anti-inflammatory effect of milk fermented by a strain of IL-10-producing Lactococcus lactis using a murine model of Crohn's disease.

Interleukin-10 (IL-10) is the most important anti-inflammatory cytokine at intestinal level, and its absence is involved in inflammatory bowel diseases. However, oral treatment with IL-10 is difficult because of its low survival in the gastrointestinal tract and systemic treatments lead to undesirable side effects. The aim of this paper was to evaluate the anti-inflammatory effect of the administration of milks fermented by Lactococcus lactis strains that produce IL-10 under the control of the xylose-inducible expression system using a trinitrobenzenesulfonic acid-induced colitis murine model. Mice that received milks fermented by L. lactis strains producing IL-10 in the cytoplasm (Cyt strain) or secreted to the product (Sec strain) showed lower damage scores in their large intestines, decreased IFN-γ levels in their intestinal fluids and lower microbial translocation to liver, compared to mice receiving milk fermented by the wild-type strain or those not receiving any treatment. The results obtained in this study show that the employment of fermented milks as a new form of administration of IL-10-producing L. lactisis effective in the prevention of inflammatory bowel disease in a murine model.