Search

Thiamine or vitamin B1, an essential micronutrient mainly involved in energy production, has a beneficial impact on the nervous system, and its deficiency can be associated with the development and progression of neurodegenerative diseases. The aim of this work was to select thiamine-producing lactic acid bacteria (LAB) and study their physiological effects using neuron cell cultures. In this study, 23 LAB able to produce thiamine were identified by growth in thiamine-free synthetic medium. Intra- and extracellular thiamine concentrations were determined using a microbiological method and results confirmed by HPLC techniques. A wide variation in vitamin production was found showing that this property was not only species specific but also a strain-dependent trait. Five of these strains were pre-selected for their capacity to produce higher concentrations of thiamine. Only the pre-treatment with the intracellular extract of Lactiplantibacillus (L.) plantarum CRL 1905 increased significantly neuronal survival in N2a cells' model of neurotoxicity (MPP+) with thiamine deficiency conditions (amprolium). Furthermore, amprolium-resistant variants of CRL 1905 were isolated by exposition of the strain to increasing concentrations of this toxic thiamine analogue. The variant A9 was able to increase more than 2 times the intracellular thiamine production of the original strain. A9 bacterial extract significantly prevented neuronal cell death and the increase of IL-6. The amprolium-resistant strain A9 showed a modulating and neuroprotective effect in an in vitro model of neurotoxicity constituting a potential bio-strategy to counteract thiamine deficiencies and thus prevent or treat neurodegenerative diseases. KEY POINTS: • LAB can produce thiamine in a species- and strain-dependant manner. • L. plantarum CRL 1905 significantly reduce MPP+-induced neurotoxicity in N2a cells. • Amprolium-resistant strain A9 has neuroprotective effect and prevents IL-6 increase.

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 vitaminproducing 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. Fil: Leblanc, Jean Guy Joseph. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Levit, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Savoy, Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; Argentina Fil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina

Mandatory fortification of foods with folic acid is being questioned by many scientists principally because of the potential adverse secondary effects associated with their excessive consumption. It has been shown that selected strains of lactic acid bacteria (LAB) are able to produce natural forms of folate and these could be included in foods to prevent deficiencies without causing adverse effects. The aim of this study was to evaluate folate production and fol gene expression by Streptococcus gallolyticus subsp. macedonicus (S. macedonicus) CRL415 under different growth conditions in vitro and to assess its potential probiotic application. Results showed that glucose as the principal carbon source, and incubation at 42 °C under controlled pH conditions (6.0) increased folate production, fol gene expression, and growth of S. macedonicus CRL415. This strain was able to produce elevated folate concentrations during milk fermentation without the need of prolonged incubation times and was able to resist conditions simulating the gastrointestinal tract. In addition, S. macedonicus was susceptible to all required antibiotics, and had a good adhesion level to intestinal cells in vitro, making it a promising candidate for biotechnological application as functional starter cultures in the dairy industry. Fil: Laiño, Jonathan Emiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Levit, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Savoy, Graciela. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Leblanc, Jean Guy Joseph. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina

Fibre content, phenolic content, antioxidant and anti-inflammatory activities were evaluated for water extracts of fruit by-products (passion fruit, orange, acerola, and mango). The impact of these extracts on microbial growth, folate production, and adhesion ability of Streptococcus thermophilus TH-4 and Lactobacillus rhamnosus LGG was investigated. Mango water extract (MWE) presented the highest phenolic content and antioxidant activity. Orange water extract (OWE) and MWE showed the best anti-inflammatory potential by decreasing the highest nitric oxide levels. When TH-4 and LGG were grown together, folate production was only stimulated by MWE. Passion fruit water extract and OWE increased the TH-4 adhesion whereas acerola water extracts and MWE improved LGG adhesion when strains were used individually. These results showed that fruit by-product water extracts (FWE), especially from mango, presented potential beneficial biological and functional properties. These FWE could be used to develop new functional antioxidant foods and natural pharmaceutical ingredients.

Fruit by-products are generated by the food industries and constitute an important environmental problem. Although these fruit residues are frequently treated as industrial waste and used mainly for animal feed, they can be good sources of nutrients and bioactive compounds. Among them, dietary fibers and phenolics are bioactive compounds that can stimulate the growth and activity (including the production of B vitamins) of beneficial microorganisms, especially lactic acid bacteria and other probiotics. Bioactive compounds have also been explored to improve the nutritional and functional properties of food products. Thus, these compounds from fruit by-products emerge as potential prebiotic ingredients. In addition to the influence on beneficial microorganisms, bioactive compounds from fruit by-products may act as natural antioxidants with an important role in preventing human health, especially in the gastrointestinal tract, from inflammatory conditions. This chapter discusses how fruit by-products can be used as prebiotics to stimulate the production of bioactive compounds by lactic acid bacteria in the gastrointestinal tract or as ingredients to promote health benefits caused by bacterial fermentation.

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. Fil: Pérez Visñuk, Daiana Emilce. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Savoy, Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; Argentina Fil: Leblanc, Jean Guy Joseph. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina

Objective: Intestinal mucositis (IM), a side effect commonly associated to cancer treatments, is a local inflammatory response that causes alterations of the intestinal structure that in turn affects nutrient absorption. Lactobacillus (L.) plantarum CRL 2130 is a riboflavin-overproducing strain that has previously been shown to provide anti-inflammatory properties. The objective of this study was to evaluate the effects of this riboflavin producing strain in a chemically induced murine mucositis model. Research Methods & Procedures: Mucositis was induced by daily injections of 5-fluororacil (5-FU) after which mice were either given L. plantarum CRL 2130, L. plantarum CRL 725 (the strain from which CRL 2130 was derived that does not overproduce riboflavin), or commercial riboflavin twice daily during the 6 days 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 anti-cancer activity. Results: Administration of L. plantarum CRL 2130 significantly attenuated the pathological changes induced by 5-FU in mice such as body weight loss, diarrhea, the shortening of villus height, increases in proinflammatory cytokine concentrations, and induced an elevated production of IL-10. In vitro assays using Caco-2 cells showed that the effectiveness of 5-FU was not affected by L. plantarum CRL 2130 and that this strain exerted an inhibitory mechanism against oxidative stress. Conclusion: These results indicate that the riboflavin-overproducing strain L. plantarum CRL 2130 could be useful to prevent mucositis during cancer treatments and would not affect the primary treatment. Fil: Levit, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Savoy, Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; Argentina Fil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Leblanc, Jean Guy Joseph. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina

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. Fil: Levit, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Savoy, Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Leblanc, Jean Guy Joseph. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina

The host immune system is an important factor to combat metastasis. In this work, it was evaluated the immunomodulation exerted by milk fermented with the probiotic strain Lactobacillus casei CRL431 (PFM) when was administered to mice in the metastatic stage of breast cancer. Mice received PFM were compared to animals given milk. PFM administration diminished metastasis in the lungs and increased the survival of the animals. Systemically, PFM administration decreased pro-inflammatory cytokines and locally in the lungs (metastatic organs) decreased F4/80+ cells, principally IL-10/F4/80+ cells. The highest percentages for CD4+ and CD4+CD8+ cells were observed in PFM group. Finally, immune cells from lungs of mice given PFM showed lower production of most cytokines evaluated when they were re-stimulated in vitro with tumour cells. The results obtained suggest that modulation of immune cells in the lungs by PFM could be a strategy to fight against tumour cells in the metastatic sites. Fil: Méndez Utz, Virginia Emilce. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Perdigon, Gabriela del Valle. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Microbiología. Cátedra de Inmunología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina

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.

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

Phallus atrovolvatus is a wild edible mushroom which is recently being cultivated in Thailand. It contains a remarkable amount of β-(1,3–1,6)-glucan, a compound known for its immune modulating properties. Crude mushroom polysaccharide (CMP) was obtained from the fruiting body of P. atrovolvatus using boiling water extraction, followed by overnight ethanol cold precipitation. CMP is composed of approximately 50% β-glucan, α-glucan, proteins, ash and other non-digestible polysaccharide. In this study, we evaluated the immune modulating activities of CMP using in vitro and in vivo models. In vitro, CMP was treated with the transfected NF-κB reporter-HEK 293 recombinant cell line, the results showed no cytotoxicity up to 500 μg/mL, and CMP treatments exhibited a higher % NF-κB luciferase expression. DiNitroBenzene Sulfonic acid (DNBS)-induced colitis mice model was used to elucidate the effects of CMP in vivo. Colitis severity was assessed using body weight trend, macroscopic scores and histological scores. Myeloperoxidase (MPO) activity and cytokine production were determined from the colon tissue and spleen, respectively. The results showed that oral consumption of 50 μg CMP/mouse/day could significantly decrease MPO activity and reduce the secretion of TNF-α, IL-6, IL-10, and IL-17A cytokines. To our knowledge, this study shows the first time the report of immune modulating activities of Phallus atrovolvatus Thai strain. The results lead to the conclusion that CMP provides two modes of actions: i) stimulating the NF-κB pathway and ii) acting as an anti-inflammatory that can protect mice against induced colitis.

This study aimed to evaluate the bioavailability and effects on the intestinal mucosa of a bioenriched fermented milk (BFM) prepared with folate-producing lactic acid bacteria, using a depletion/repletion BALB/c mice model. Five Streptococcus thermophilus strains were combined with Lactobacillus plantarum 16cv and the combination that resulted in the best folate production was used for preparation of BFM. The folate content in BFM, prepared under controlled conditions (pH 6.0, 42 °C, 70 rpm, 24 h), was 321.1 ± 14.1 ng/mL. Results for mice fed with BFM were compared to those fed with other diets. The BFM group presented an increase in hemoglobin, hematocrit and red blood cells, and the villi height/crypt depth ratio was similar to that of animals receiving milk supplemented with commercial folic acid. The strains were sensitive to most tested antibiotics and lacked virulence genes, indicating that consumption of BFM may be a promising alternative to increase intake of folate. Fil: Cucick, Ana Clara C.. Universidade de Sao Paulo; Brasil Fil: Gianni de Carvalho, Katia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Planta Piloto de Procesos Industriales Microbiológicos; Argentina Fil: Todorov, Svetoslav D.. Universidade de Sao Paulo; Brasil Fil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Leblanc, Jean Guy Joseph. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Franco, Bernadette D. G. M.. Universidade de Sao Paulo; Brasil

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 anti-inflammatory 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 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 anti-inflammatory 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. Fil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Levit, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Savoy, Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; Argentina Fil: Leblanc, Jean Guy Joseph. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina

Inflammatory bowel diseases (IBD), such as Crohn's disease and ulcerative colitis, is characterized by extensive inflammation due to dysregulation of the innate and adaptive immune system whose exact etiology is not yet completely understood. Currently there is no cure for IBD, thus the search for new molecules capable of controlling IBD and their delivery to the site of inflammation are the goal of many researchers. The aim of this work was to evaluate the anti-inflammatory effect of the administration of milks fermented by a Lactococcus (L.) lactis strain producing 15-lipoxygenase-1 (15-LOX-1) using a trinitrobenzenesulfonic acid-induced IBD mouse model. The results obtained demonstrated that 15-LOX-1 producing L. lactis was effective in the prevention of the intestinal damage associated to inflammatory bowel disease in a murine model. The work also confirmed previous studies showing that fermented milk is an effective form of administration of recombinant lactic acid bacteria expressing beneficial molecules. Fil: Saraiva, Tessália D. L.. Universidade Federal do Minas Gerais; Brasil Fil: Morais, Kátia. Universidade Federal do Minas Gerais; Brasil Fil: Pereira, Vanessa B.. Universidade Federal do Minas Gerais; Brasil Fil: de Azevedo, Marcela. Universidade Federal do Minas Gerais; Brasil Fil: Santos Rocha, Clarissa. Universidade Federal do Minas Gerais; Brasil Fil: Castro Prosperi, Camila. Universidade Federal do Minas Gerais; Brasil Fil: Gomes Santos, Ana C.. Universidade Federal do Minas Gerais; Brasil Fil: Bermudez Humaran, Luis. Institut National de la Recherche Agronomique; Francia Fil: Caetano Faria, Ana M.. Universidade Federal do Minas Gerais; Brasil Fil: Blottiere, Hervé M.. Institut National de la Recherche Agronomique; Francia Fil: Langella, Philippe. Institut National de la Recherche Agronomique; Francia Fil: Miyoshi, Anderson. Universidade Federal do Minas Gerais; Brasil Fil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Leblanc, Jean Guy Joseph. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Azevedo, Vasco. Universidade Federal do Minas Gerais; Brasil

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. Fil: del Carmen, Silvina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina Fil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina Fil: Levit, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina Fil: Azevedo, Vasco. Universidade Federal Do Minas Gerais; Fil: Langella, Philippe. Institut National de la Recherche Agronomique; Francia Fil: Bermúdez Humarán, Luis G.. Institut National de la Recherche Agronomique; Francia Fil: Leblanc, Jean Guy Joseph. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina

Objective: Obesity is associated with alterations in intestinal microbiota and immunity. The aim of this study was to determine the effect of probiotic Lactobacillus casei CRL 431 administration on intestinal and humoral immune response, clinical parameters, and gut microbiota was evaluated using a high-fat diet to induce obesity in a mouse model. Methods: Adult mice received a conventional balanced diet or a high-fat diet supplemented with milk, milk fermented by Lactobacillus casei (FM), L. casei as suspension, or water over 60d. Histology of liver and small intestine (SI), immunoglobulin A-positive cells and macrophages in SI, phagocytic activity of spleen and peritoneal macrophages, and humoral immune response to ovalbumin were studied. Clinical parameters in serum and gut microbiota were also analyzed. Results: FM was the most effective supplement for decreasing body weight and clinical parameters in serum. The histology of liver and SI was also improved in obese mice given FM. These animals had increased numbers of immunoglobulin A-positive cells and macrophages in SI. The gut microbiota showed that obese mice given probiotics had increased Bacteroides and bifidobacteria. Administration of FM or L. casei as suspension enhanced the phagocytic activity of macrophages. The anti-ovalbumin specific immune response was not increased by any supplement assayed. Conclusion: Administration of probiotics to obese hosts improved the gut microbiota and the mucosal immunity altered by obesity, down-regulated some biochemical parameters in blood associated with metabolic syndrome, and decreased liver steatosis. These results demonstrate the potential use of probiotics in obese individuals to decrease the body weight and to improve the biochemical and immunologic parameters altered by obesity. Fil: Novotny Núñez, Ivanna. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Maldonado Galdeano, María Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Microbiología; Argentina Fil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Perdigon, Gabriela del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Microbiología; Argentina

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 Fil: Aragón, Félix Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Carino, Silvia. Universidad Nacional de Tucumán. Facultad de Odontología; Argentina Fil: Perdigon, Gabriela del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; Argentina Fil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina

Protein–energy malnutrition (PEM) causes a significant impairment of the immune system, the thymus being one of the most affected organs. It has been demonstrated that the administration of probiotic fermented milk (PFM) recovered the intestinal barrier, histological alterations and mucosal and systemic immune functions in a non-severe malnutrition model using BALB/c mice. The aim of the present study was to evaluate, in the same model of malnutrition, the effect of a PFM added to a re-nutrition diet on the recovery of the thymus, analysing histological and functional alterations caused by malnutrition. Mice were undernourished and divided into three groups according to the dietary supplement received during re-nutrition: milk, PFM or its bacterial-free supernatant (BFS). They were compared with well-nourished and malnourished mice. PFM was the most effective re-nutrition supplement to improve the histology of the thymus, decreasing cellular apoptosis in this organ and recovering the percentage of CD4þ/CD82 single-positive thymocytes. Immature doublepositive thymocytes were increased in the malnourished control (MC). The production of different cytokines in the thymus was increased in mice given PFM, compared with the mice that received other dietary supplements and MC. Mice given the BFS presented an improvement in the thymus similar to those that received milk. We demonstrated the importance of the whole PFM supplementation on the histological and functional recovery of the thymus in a non-severe PEM model. Fil: Novotny Núñez, Ivanna. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia para Lactobacilos (i); Argentina; Fil: Maldonado Galdeano, María Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia para Lactobacilos (i); Argentina; Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Microbiología; Argentina; Fil: Carmuega, Esteban. Centro de Estudios en Nutrición Infantil; Argentina; Fil: Weill, Ricardo. DANONE. Departamento de investigación y Desarrollo; Argentina; Fil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia para Lactobacilos (i); Argentina; Fil: Perdigón, Gabriela del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia para Lactobacilos (i); Argentina; Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Microbiología; Argentina

Background: Immunotherapy by using non-specific vaccines has proven to be effective in experimental animal models and also in patients suffering cancer. In the present work, the effectiveness of this immunotherapy was evaluated using a murine breast cancer model and a polymicrobial vaccine. Methodology/Principal: Mice bearing injected with tumor cells from the spontaneous syngeneic mammary adeno carcinoma M3 were used as breast cancer model. The immune adjuvant effect of the vaccine was analyzed in comparison or in the presence of doxorubicin. Tumor volume was calculated. Tumor, spleen and lymph nodes were processed for histological observations and to determinate the percentage of CD11c (+) cells. Results: Mice treated with the vaccine or with doxorubicin decreased tumor growth, with less tumor cell invasion. Tumor tissues showed decreased necrosis and nuclear areas in mice that received any of the treatments under study, compared with the control group. The benefits of vaccination were associated to stimulation of the immune response. More hyperplasia of the red and white pulp, and increased marginal megakaryocytes were observed in the spleens from mice treated with the vaccine. CD11c (+) cells did not increase in tumor draining nodes by the immune stimulating effect of the vaccine; however, his treatment increased CD11c (+) cells in the spleen and tumor. Conclusions: A non-specific vaccine used as immunotherapy can be used to prolong an equilibrium phase in he tumor growth, similar to the doxorubicin treatment used in the model, although by different mechanisms. Non synergic effect was observed in the group treated with both vaccine and doxorubicin (low dose). Future studies should be necessary to evaluate the correct combination of vaccination and cytotoxic drug can be used for this purpose and to achieve increased activated dendritic cells in the tumor draining lymph nodes. Fil: de Gregorio, Vanessa Elizabeth. Universidad Nacional de Tucumán. Facultad de Odontología; Argentina Fil: Carino, Silvia. Universidad Nacional de Tucumán. Facultad de Odontología; Argentina Fil: Valdéz, Juan Carlos. Universidad Nacional de Tucuman. Facultad de Bioquimica, Quimica y Farmacia. Instituto de Microbiologia. Cátedra de Inmunología; Argentina Fil: Castillo, Silvio Eugenio. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; Argentina Fil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina

Several studies have shown that specific probiotic strains are able to prevent the development of some diseases such as inflammatory bowel diseases (IBD) and certain types of cancer. Some of the proposed mechanisms of action that account for their beneficial effects include changes in the gut microbiota, stabilization of the intestine’s permeability barrier, regulation of the host immune responses, and reduction of the oxidative stress due to their antioxidant enzyme production. This chapter will examine some examples of studies using animal models and human clinical trials where probiotics were shown to be effective in the prevention or treatment of IBD and intestinal and nonintestinal cancers, and describe the current knowledge of their mechanisms of action. Probiotics could potentiate conventional treatments and reduce undesirable side effects and thus improve the general well-being of subjects that suffer from these diseases.

Background: Inflammatory bowel disease (IBD), such as Crohn’s disease and ulcerative colitis, are characterized by extensive inflammation due to dysregulation of the innate and adaptive immune system whose exact etiology is not yet completely understood. Currently there is no cure for IBD, thus the search for new molecules capable of controlling IBD and their delivery to the site of inflammation are the goal of many researchers. The aim of this work was to evaluate the anti-inflammatory effect of the oral administration of a Lactococcus (L.) lactis strain producing 15-lipoxygenase-1 (15-LOX-1) using a dextran sodium sulfate (DSS)-induced IBD mouse model. Methods: The anti-inflammatory strain L. lactislacti NCDO 2118 was modified to produce active 15-LOX-1 and tested in in a DSS induced IBD mouse model. Results: This 15-LOX-1 producing L. lactis was effective in the prevention of the intestinal damage associated to inflammatory bowel disease in a murine model and decreased pro-inflammatory cytokines such as IFN-γ and IL-4 while increasing the anti-inflammatory cytokine IL-10. L. lactis NCDO 2118 acts not just as a tool to delivery 15-LOX-1 in the inflamed gut mucosa but still retains its anti-inflammatory effects. Conclusions: This strain could be used in novel adjunct IBD treatment protocols. Fil: Carvalho, Rodrigo. Universidade Federal do Minas Gerais; Brasil Fil: Morais, Kátia. Universidade Federal do Minas Gerais; Brasil Fil: Bastos Pereira, Vanessa. Universidade Federal do Minas Gerais; Brasil Fil: Gomes Santos, Ana Cristina. Universidade Federal do Minas Gerais; Brasil Fil: Diniz Luerce, Tessalia. Universidade Federal do Minas Gerais; Brasil Fil: de Azevedo, Marcela. Universidade Federal do Minas Gerais; Brasil Fil: Santos Rochat, Clarissa. Universidade Federal do Minas Gerais; Brasil Fil: Severiano de Sousa, Cassiana. Universidade Federal do Minas Gerais; Brasil Fil: Prósperi, Camila. Universidade Federal do Minas Gerais; Brasil Fil: Carmona Cara, Denise. Universidade Federal do Minas Gerais; Brasil Fil: Caetano Faria, Ana María. Universidade Federal do Minas Gerais; Brasil Fil: Bermudez-Humaran, Luis. Institut National de la Recherche Agronomique; Francia Fil: Blottiere, Hervé. Institut National de la Recherche Agronomique; Francia Fil: Langella, Philippe. Institut National de la Recherche Agronomique; Francia Fil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina Fil: Pereira Figueiredo, Henrique Cesar. Universidade Federal do Minas Gerais; Brasil Fil: Leblanc, Jean Guy Joseph. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina Fil: Miyoshi, Anderson. Universidade Federal do Minas Gerais; Brasil Fil: Azevedo, Vasco. Universidade Federal do Minas Gerais; Brasil

Inflammatory bowel diseases (IBDs) affect the gastrointestinal tract and are characterized by recurrent inflammation that requires lifelong therapies. Probiotics such as lactic acid bacteria (LAB) have been proposed to complement current treatment protocols for these patients; however, their characteristics are strain dependent. In this regard, certain novel characteristics are only possible through the genetic modification of these beneficial micro-organisms. Different delivery systems, such as protein delivery of anti-oxidant enzymes and anti-inflammatory cytokines, have been shown to be effective in preventing and treating IBD in animal models. In this study, the safety of the recombinant LAB (recLAB) Streptococcus thermophilus CRL807: CAT, S. thermophilus CRL807: SOD, Lactococcus lactis NCDO2118 pXILCYT: IL-10, L. lactis MG1363 pValac: IL-10 and L. lactis MG1363 pGroESL: IL-10 with proven beneficial effects was compared to their progenitor strains S. thermophilus CRL807, L. lactis NCDO2118 or L. lactis MG1363. The prolonged administration of these genetically modified strains showed that they were just as safe as the native strains from which they derive, as demonstrated by normal animal growth and relative organ weights, absence of microbial translocation from the gastrointestinal tract, normal blood parameters and intestinal histology. The results show the potential use of these recLAB in future therapeutic formulations; however, the use of modern bio-containment systems is required for the future acceptance of these recLAB by the medical community and patients with IBD. Fil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina Fil: del Carmen, Silvina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina Fil: Chatel, Jean Marc. INRA and AgroParisTech; Francia Fil: Azevedo, Vasco. Universidade Federal do Minas Gerais; Brasil Fil: Langella, Philippe. INRA and AgroParisTech; Francia Fil: Bermudez Humaran, Luis. INRA and AgroParisTech; Francia Fil: Leblanc, Jean Guy Joseph. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina

Salmonella produces infections of different nature and severity depending of many factors including the Salmonella serovar involved, strain virulence, infective dose, host animal species, age and immune status of the host. The treatments against Salmonella infections rely on supportive and antibiotic therapy to eliminate the pathogen, but the development of resistance by Salmonella to the antimicrobials most commonly used limits its efficacy. Other disadvantages of antibiotic treatments are that they can lead to acute diarrhea (antimicrobials normally induce an imbalance of intestinal bacterial flora) and may produce chronic toxicity. Considering this undesired consequences of antibiotics and because at the present there are no effective oral vaccines which protect against salmonellosis, scientists have been searching for alternative methods to control enteric infections. In the present review, probiotics are proposed as an attractive possibility to attend this concern. Probiotic are live microorganisms, which when administered in adequate amounts confer a health benefit on the host. In vitro and in vivo studies showed the effectiveness of probiotic administration in the prevention or in the treatment against Salmonella infection. There are several mechanisms by which probiotic strains might exert their effects. They include non immune mechanisms (stabilization of the gut mucosal barrier, competition for adhesion, secretion of antimicrobial substances, etc.) and the modulation of the mucosal and systemic immune responses. These mechanisms are species and/or strain specific. There are also evidences that in some cases, a mix of probiotic strains can be more useful than each strain alone against this infection. In addition, the presence of one or more probiotic strains in a fermented product can improve the beneficial properties of the probiotic strains involved. It was also reviewed the security of probiotics administration after Salmonella infection in healthy host and in immunosuppressed or babies hosts. Although, the major part of the researches were performed in animal models through in vivo assays or by in vitro studies using human cell lines, some studies carried out in humans to verify the probiotic effects were also addressed in the present review. Nevertheless, is of critical importance to perform more clinical trials in humans to validate the results obtained with each specific probiotic strain or probiotic product.

Lactic acid bacteria (LAB) represent a heterogeneous group of microorganisms that are naturally present in many foods and possess a wide range of therapeutic properties. The aim of this paper is to present an overview of the current expanding knowledge of the mechanisms by which LAB and other probiotic microorganisms participate in the prevention and treatment of inflammatory bowel diseases. These include changes in the gut microbiota, stimulation of the host immune responses, and reduction of the oxidative stress due to their antioxidant properties. A brief overview of the uses of genetically engineered LAB that produce either antioxidant enzymes (such as catalase and superoxide dismutase) or anti-inflammatory cytokines (such as IL-10) will also be discussed. This paper will show that probiotics should be considered in treatment protocols of IBD since they provide many beneficial effects and can enhance the effectiveness of traditional used medicines. Fil: del Carmen, Silvina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Miyoshi, Anderson. Universidade Federal de Minas Gerais; Brasil Fil: Santos Rocha, Clarissa. Universidade Federal de Minas Gerais; Brasil Fil: Azevedo, Vasco. Universidade Federal de Minas Gerais; Brasil Fil: Leblanc, Jean Guy Joseph. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina

Reactive oxygen species are involved in various aspects of intestinal inflammation and tumor development. Decreasing their levels using antioxidant enzymes, such as catalase (CAT) or superoxide dismutase (SOD) could therefore be useful in the prevention of certain diseases. Lactic acid bacteria (LAB) are ideal candidates to deliver these enzymes in the gut. In this study, the anti-inflammatory effects of CAT or SOD producing Lwere evaluated using a trinitrobenzenesulfonic acid (TNBS) induced Crohn's disease murine model. Engineered Lactobacillus casei BL23 strains producing either CAT or SOD, or the native strain were given to mice before and after intrarectal administration of TNBS. Animal survival, live weight, intestinal morphology and histology, enzymatic activities, microbial translocation to the liver and cytokines released in the intestinal fluid were evaluated. The mice that received CAT or SOD-producing Lshowed a faster recovery of initial weight loss, increased enzymatic activities in the gut and lesser extent of intestinal inflammation compared to animals that received the wild-type strain or those that did not receive bacterial supplementation. Our findings suggest that genetically engineered Lthat produce antioxidant enzymes could be used to prevent or decrease the severity of certain intestinal pathologies. (C) 2010 Elsevier B.V. All rights reserved.

The prevention of pathogen infections is one of the most extensively studied effects of probiotics. L. casei CRL 431 is a probiotic bacterium and its effects on the gut immune cells have been extensively studied. The aim of the present study was to determine, using a mouse model, the preventive and therapeutic effect of L. casei CRL 431 to achieve protection against Salmonella enteritidis serovar Typhimurium infection. In both previous and continuous (previous and post-infection) probiotic administration, the mechanisms induced by this lactic acid bacteria on the first line of intestinal defense (non-specific barrier and the innate immune cells associated to the gut), as a way to understand some of the mechanisms involved in the protection against Salmonella enteritidis serovar Typhimurium, were analyzed. The results obtained demonstrated that 7 days L. casei CRL 431 administration before infection decreased the severity of the infection with Salmonella enteritidis serovar Typhimurium, demonstrating that the continuous administration (even after infection) had the best effect. This continuous administration diminished the counts of the pathogen in the intestine as well as its spread outside this organ. Several mechanisms and cells are involved in this protective effect against Salmonella enteritidis serovar Typhimurium. L. casei CRL 431 acted on cells of the innate and adaptive immune response. The probiotic administration decreased the neutrophil infiltration with the consequent diminution of intestinal inflammation; activated the macrophage phagocytic activity in different sites such as Peyer's patches, spleen and peritoneum; and increased the number of IgA + cells in the lamina propria of the small intestine which was correlated with increased release of s-IgA specific against the pathogen in the intestinal fluids. The mechanism of the inhibition of cellular apoptosis was not involved.

Lactic acid bacteria (LAB) are present in many foods such as yoghurt and are frequently used as probiotics to favour some biological functions in the host. Many investigators have evaluated the therapeutic effects of yoghurt and LAB commonly used in yoghurt production against diseases such as cancer, infection, and gastrointestinal disorders. The increase of immune cell activity in the prevention of cancer by LAB consumption has also been described. Another possible explanation for the preventive effect of probiotics on carcinogenesis is their effect on other bacteria in the intestine. Probiotics may suppress the growth of bacteria that convert procarcinogens into carcinogens, thereby reducing the amount of carcinogens in the intestine. The present review is focused on two types of cancer in which milk fermented by LAB may show a beneficial effect: colon cancer and breast cancer. Fil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Matar, Chantal. Université de Moncton; Francia Fil: Perdigon, Gabriela del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina

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.

The aim of this work was to develop a Streptococcus (S.) thermophilus strain with improved anti-inflammatory properties due to the incorporation of the therapeutic cDNA delivery plasmid pValac::il-10. To achieve this purpose, cells of S. thermophilus CRL807, previously selected as being an important anti-inflammatory strain, were electroporated with pValac::il-10 plasmid. In order to confirm the functionality of the developed strain, it was co-cultured with human epithelial cells Caco-2 and the production of IL-10 was evaluated by ELISA. Bacterial suspensions of S. thermophilus CRL807 containing pValac::il-10 plasmid or of the wild-type (WT) strain were administered in vivo using a murine model of intestinal inflammation. The animals treated with S. thermophilus CRL807 pValac::il-10 showed a lower body weight loss, microbial translocation to liver and damage scores in their intestines at macroscopical and microscopic levels. Furthermore, a significant increase was observed in the concentration of IL-10 in the intestinal contents of these mice compared to the rest of the experimental groups, accompanied by decreased levels of pro-inflammatory cytokines. The insertion of the therapeutic pValac::il-10 plasmid increased the intrinsic anti-inflammatory activity (synergetic effect) of S. thermophilus CRL807 which could be included in novel treatment protocols for inflammatory bowel diseases. Fil: del Carmen, Silvina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina Fil: Miyoshi, Anderson. Universidade Federal do Minas Gerais; Brasil Fil: Azevedo, Vasco. Universidade Federal do Minas Gerais; Brasil Fil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina Fil: Leblanc, Jean Guy Joseph. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina

Inflammatory Bowel Diseases (IBD) are disorders of the gastrointestinal tract characterized by recurrent inflammation that requires lifelong treatments. Probiotic microorganisms appear as an alternative for these patients; however, probiotic characteristics are strain dependent and each probiotic needs to be tested to understand the underlining mechanisms involved in their beneficial properties. Genetic modification of lactic acid bacteria (LAB) was also described as a tool for new IBD treatments.The first part of this review shows different genetically modified LAB (GM-LAB) described for IBD treatment since 2000.Then, the two principally studied strategies are discussed (i) GM-LAB producing antioxidant enzymes and (ii) GM-LAB producing the anti-inflammatory cytokine IL-10. Different delivery systems, including protein delivery and DNA delivery, will also be discussed. Studies show the efficacy of GM-LAB (using different expression systems) for the prevention and treatment of IBD, highlighting the importance of the bacterial strain selection (with anti-inflammatory innate properties) as a promising alternative. These microorganisms could be used in the near future for the development of therapeutic products with anti-inflammatory properties that can improve the quality of life of IBD patients. Fil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: del Carmen, Silvina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Chatel, Jean Marc. Institut National de la Recherche Agronomique; Francia Fil: Miyoshi, Anderson. Universidade Federal do Minas Gerais; Brasil Fil: Azevedo, Vasco. Universidade Federal do Minas Gerais; Brasil Fil: Langella, Philippe. Institut National de la Recherche Agronomique; Francia Fil: Bermudez Humaran, Luis G.. Institut National de la Recherche Agronomique; Francia Fil: Leblanc, Jean Guy Joseph. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina

INTRODUCTION: Antitumour activity is one of the health-promoting effects attributed to the lactic acid bacteria and their products of fermentation. Previous studies in mice demonstrated that bioactive compounds released in milk fermented by Lactobacillus helveticus R389 contribute to its immunoenhancing and antitumour properties. The aim of the present work was to study the effects of the consumption of milk fermented by L. helveticus R389 or its proteolytic-deficient variant, L. helveticus L89, on a murine hormone-dependent breast cancer model. METHODS: Mice were fed with milk fermented by L. helveticus R389 or L. helveticus L89, during 2 or 7 days. The tumour control group received no special feeding. At the end of the feeding period, the mice were challenged by a subcutaneous injection of tumour cells in the mammary gland. Four days post-injection, the mice received fermented milk on a cyclical basis. The rate of tumour development and the cytokines in serum, mammary gland tissue and tumour-isolated cells were monitored. Bcl-2-positive cells in mammary glands and cellular apoptosis in tumour tissue were also studied. RESULTS: Seven days of cyclical administration of milk fermented by either bacterial strain delayed or stopped the tumour development. Cytokines demonstrated that L. helveticus R389 modulated the immune response challenged by the tumour. IL-10 and IL-4 were increased in all the samples from this group. In comparison with the tumour control, all test groups showed a decrease of IL-6, a cytokine involved in oestrogen synthesis. Seven days of cyclical feeding with milk fermented by L. helveticus R389 produced an increase in the number of apoptotic cells, compared with all other groups. CONCLUSION: This study demonstrated that 7 days of cyclical administration of milk fermented by both strains of L. helveticus diminishes tumour growth, stimulating an antitumour immune response. Compounds released during milk fermentation with L. helveticus R389 would be implicated in its immunoregulatory capacity on the immune response in mammary glands and tumour, which were correlated with the cytokines found at the systemic level. The milk fermented by L. helveticus R389 was able to modulate the relationship between immune and endocrine systems (by IL-6 diminution), which is very important in oestrogen-dependent tumour and induced cellular apoptosis. Fil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; Argentina. Université de Moncton; Canadá Fil: Matar, Chantal. Université de Moncton; Canadá Fil: LeBlanc, Nicole. Université de Moncton; Canadá Fil: Perdigon, Gabriela del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; Argentina

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. Fil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina Fil: Leblanc, Jean Guy Joseph. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina

Inflammatory bowel diseases affect the quality of life of many people through the world. Previous studies demonstrated the anti-inflammatory potential of a yoghurt prepared with a pool of candidate probiotic strains of Lactobacillus (L.) delbrueckii subsp. bulgaricus and Streptococcus (S.) thermophilus from the CERELA Culture Collection. Considering that the probiotic effects are strain specific, the aim of this work was to select from this yoghurt, the LAB strains related to this anti-inflammatory effect and prove their potential in vitro and in vivo. M&M: L. delbrueckii subsp. bulgaricus (CRL861, 863, 864, 866, 869, 871, 872 and 887) and S. thermophilus (CRL806 and 807) were grown separately to obtain the fermented milks (FM). The in vitro anti-inflammatory capacity of each FM was studied in co-culture with mononuclear cells isolated from Peyer’s patches of healthy mice, by evaluating the cytokines IFNg and IL-10 in the supernatants. The in vitro selected FM were administered to healthy mice and to mice inoculated with TNBS (colitis model). Pro-inflammatory cytokines (IFNg, IL-17) and the regulatory cytokine IL-10 were evaluated in their intestines. Results: The in vitro studies demonstrated that the cocultures with FMs obtained with S. thermophilus CRL807 and L. bulgaricus 864 showed increased IL10/IFNγ ratios. This IL10/IFNγ ratio also increased in the intestinal fluids of healthy mice given these FMs. These mice also increased the ratio of IL10+ cells/IL17+ cells in their

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. Fil: Aragón, Félix Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina Fil: Perdigon, Gabriela del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Microbiología; Argentina Fil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina

Background: Oral treatment with Lactococcus (L.) lactis strains secreting the anti-inflammatory cytokine IL-10 has previously shown success as a therapy for inflammatory bowel diseases (IBD). Goals: Our aim was to compare the protective effects of IL-10, delivered by recombinant lactoccoci using two novel expression systems, in a murine colitis model mimicking the relapsing nature of IBD. The first system is based on a Stress-Inducible Controlled Expression (SICE) system for the production and delivery of heterologous proteins at mucosal surfaces and the second allows the delivery to the host cells of an il-10 cDNA cassette, harbored in a eukaryotic DNA expression vector (pValac). Study: Colitis was induced in female BALB/c mice by intrarectal injection of 2,4,6-trinitrobenzenesulphonic acid (TNBS). Mice that recovered received one of the bacteria treatments or saline solution orally during 14 days. Colitis was reactivated 25 days after the first TNBS injection with a second TNBS challenge. Three days after colitis reactivation, cytokine profiles and inflammation in colon samples were evaluated. Results: Animals (N=9) receiving L. lactis strains secreting IL-10 using SICE system or delivering pValac:il-10 plasmid showed lower weight loss (p

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.

Inflammatory bowel disease (IBD) is a term used to describe a group of intestinal disorders in which inflammation is a major feature. Although rare forms of IBD exist, these diseases normally pertain to ulcerative colitis (UC) (Head & Jurenka, 2003) and Crohn’s disease (CD) (Baumgart & Sandborn, 2007). There is evidence that these do not represent distinct conditions but rather are the same disease with shared etiological factors (Price, 1992); however, clinical manifestations (such as the exact location of the pathology or the affected individual’s immunological and constitutional endowment) are distinctive between both. Despite many years of study, the exact etiology and pathogenesis of these disorders remain unclear but great advances have been made using experimental animal models and have provided insights into the complex, multi-factorial processes and mechanisms that can result in chronic intestinal inflammation (Elson & Weaver, 2003). The aim of this chapter is to present an overview of the current expanding knowledge of the mechanisms by which lactic acid bacteria and other probiotic microorganisms participate in the prevention and treatment of IBD and how genetic engineering techniques can be used to improve their effectiveness or create novel therapeutic strains. In the following sections, the mechanisms by which these beneficial microorganisms exert their therapeutic effects, which include changes in the gut microbiota, stimulation of the host immune responses, enhancement of intestinal barrier function and reduction of the oxidative stress due to their antioxidant properties will be discussed. Fil: Leblanc, Jean Guy Joseph. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: del Carmen, Silvina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Alvarenga Lima, Fernanda. Universidade Federal de Minas Gerais; Brasil Fil: Zurita Turk, Meritxell. Universidade Federal de Minas Gerais; Brasil Fil: Miyoshi, Anderson. Universidade Federal de Minas Gerais; Brasil Fil: Azevedo, Vasco. Universidade Federal de Minas Gerais; Brasil Fil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina

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. Fil: Maldonado Galdeano, María Carolina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Novotny Núñez, Ivanna. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Carmuega, Esteban. Nutritia; Argentina Fil: Weill, Ricardo. DANONE. Departamento de Investigación y Desarrollo; Argentina Fil: Perdigon, Gabriela del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; Argentina

Crohn's disease and ulcerative colitis, two forms of inflammatory bowel disease, are important problems in industrialized countries. The complete etiology of these two diseases is still unknown but likely involves genetic, environmental, and immunological factors. The aim of the present work was to determine whether the anti-inflammatory effects reported for yoghurt in acute trinitrobenzene sulfonic acid-induced intestinal inflammation in mice also could prevent or attenuate the recurrent intestinal inflammation, thus maintaining remission. The innate response also was evaluated through participation of Toll-like receptors (TLRs) and the analysis of T-cell populations to determine the effects of yoghurt in an acute inflammatory bowel disease model. Yoghurt exerted a beneficial effect on acute intestinal inflammation by regulating T-cell expansion and modulating the expression of TLRs, with decrease of TLR4+ and increase of TLR9z cells. The anti-inflammatory effect of yoghurt also was demonstrated in a recurrent inflammation model. Yoghurt administration during the remission phase prevented the recurrence of inflammation without producing undesirable side effects. The yoghurt effect may be mediated by increased interleukin 10 production and changes in intestinal microbiota. Fil: Chaves, Analia Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Perdigon, Gabriela del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Universidad Nacional de Tucuman. Facultad de Bioquimica, Quimica y Farmacia. Instituto de Microbiologia. Cátedra de Inmunología; Argentina Fil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina

Background Diarrheal infections caused by Salmonella, are one of the major causes of childhood morbidity and mortality in developing countries. Salmonella causes various diseases that range from mild gastroenteritis to enteric fever, depending on the serovar involved, infective dose, species, age and immune status of the host. Probiotics are proposed as an attractive alternative possibility in the prevention against this pathogen infection. Previously we demonstrated that continuous Lactobacillus casei CRL 431 administration to BALB/c mice before and after challenge with Salmonella enterica serovar Typhimurium (S. Typhimurium) decreased the severity of Salmonella infection. The aim of the present work was to deep into the knowledge about how this probiotic bacterium exerts its effect, by assessing its impact on the expression and secretion of pro-inflammatory (TNFα, IFNγ) and anti-inflammatory (IL-10) cytokines in the inductor and effector sites of the gut immune response, and analyzing toll-like receptor (TLR2, TLR4, TLR5 and TLR9) expressions in both healthy and infected mice. Results Probiotic administration to healthy mice increased the expression of TLR2, TLR4 and TLR9 and improved the production and secretion of TNFα, IFNγ and IL-10 in the inductor sites of the gut immune response (Peyer's patches). Post infection, the continuous probiotic administration, before and after Salmonella challenge, protected the host by modulating the inflammatory response, mainly in the immune effector site of the gut, decreasing TNFα and increasing IFNγ, IL-6 and IL-10 production in the lamina propria of the small intestine. Conclusions The oral administration of L. casei CRL 431 induces variations in the cytokine profile and in the TLRs expression previous and also after the challenge with S. Typhimurium. These changes show some of the immune mechanisms implicated in the protective effect of this probiotic strain against S. Typhimurium, providing an alternative way to reduce the severity of the infection.

Lactic acid bacteria (LAB) represent a heterogeneous group of microorganisms that are naturally present in many foods and possess a wide range of therapeutic properties. The aim of this paper is to present an overview of the current expanding knowledge of one of the mechanisms by which LAB and other probiotic microorganisms participate in the prevention and treatment of gastrointestinal inflammatory disease through their immune-modulating properties. A special emphasis will be placed on the critical role of the anti-inflammatory cytokine IL-10, and a brief overview of the uses of genetically engineered LAB that produce this important immune response mediator will also be discussed. Thus, this paper will demonstrate the critical role that IL-10 plays in gastrointestinal inflammatory diseases and how probiotics could be used in their treatment. Fil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: del Carmen, Silvina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Zurita Turk, Meritxell. Universidade Federal de Minas Gerais; Brasil Fil: Santos Rocha, Clarissa. Universidade Federal de Minas Gerais; Brasil Fil: van de Guchte, Maarten. Institut National de la Recherche Agronomique; Francia Fil: Azevedo, Vasco. Universidade Federal de Minas Gerais; Brasil Fil: Miyoshi, Anderson. Universidade Federal de Minas Gerais; Brasil Fil: Leblanc, Jean Guy Joseph. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina

Lactic acid bacteria (LAB) represent a heterogeneous group of microorganisms that are naturally present in many foods. Some selected strains are frequently added as probiotics in order to confer specific benefits to consumers. Many studies have shown that LAB possess therapeutic properties since they are able to prevent the development of some diseases, as shown mostly on animal models for cancer, infections and gastrointestinal disorders such as intestinal inflammation. They have been shown to regulate mucosal immune responses by modulating the production and liberation of regulatory agents such as cytokines by the host. Some of these cytokines, such as the anti-inflammatory interleukin-10 (IL-10), modulate the inflammatory immune response, thus immunomodulation is a mechanism by which LAB can prevent certain inflammatory bowel diseases (IBD). Since oxidative stress participates to the inflammatory processes and to the appearance of damages in pathologies of the gastrointestinal tract of humans such as IBD, LAB could also prevent inflammation by eliminating reactive oxygen species (ROS) through the activity of antioxidant enzymes. Engineering LAB to produce either antioxidant enzymes (such as catalases and superoxide dismutases) or anti-inflammatory cytokines (such as IL-10) is a strategy currently exploited by several groups. These novel strains have successfully been used to prevent inflammatory bowel diseases in animal models and could be evaluated in human clinical trials. Here, we present an overview of the current knowledge of the mechanisms by which LAB can be used to prevent undesired intestinal inflammatory responses. Fil: Leblanc, Jean Guy Joseph. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Perdigon, Gabriela del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; Argentina Fil: Miyoshi, Anderson. Universidade Federal de Minas Gerais; Brasil Fil: Rochat, Tatiana. Institut National de la Recherche Agronomique; Francia Fil: Bermudez Humaran, Luis. Institut National de la Recherche Agronomique; Francia Fil: Langella, Philippe. Institut National de la Recherche Agronomique; Francia Fil: Sesma, Fernando Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Azevedo, Vasco. Universidade Federal de Minas Gerais; Brasil

Reactive oxygen species, such as hydrogen peroxide (H2O 2), are involved in various aspects of tumour development. Decreasing their levels can therefore be a promising approach for colon cancer prevention. The objective of this study was to evaluate the effect of catalase-producing Lactococcus lactis on the prevention of an experimental murine 1,2-dimethylhydrazine (DMH)-induced colon cancer. DMH-treated BALB/c mice received either a catalase-producing L. lactis strain or the isogenic non-catalase-producing strain as a control, whereas other untreated mice did not receive bacterial supplementation. Catalase activity and H2O 2 levels in intestinal fluids and blood samples were measured, and changes in the histology of the large intestines during tumour progression were evaluated. The catalase-producing L. lactis strain used in this study was able to slightly increase catalase activities in DMH-treated mice (1.19 ± 0.08 U ml-1) and reduce H2O2 levels (3.4 ± 1.1 μM) compared to (i) animals that received the non-catalase-producing strain (1.00 ± 0.09 U ml-1, 9.0 ± 0.8 μM), and (ii) those that did not receive bacterial supplementation (1.06 ± 0.07 U ml-1, 10.0 ± 1.1 μM). Using the histopathological grading scale of chemically induced colorectal cancer, animals that received the catalase-producing L. lactis had a significantly lesser extent of colonic damage and inflammation (2.0 ± 0.4) compared to animals that received the non-catalase-producing L. lactis (4.0 ± 0.3) or those that did not receive bacterial supplementation (4.7 ± 0.5). The catalase-producing L. lactis strain used in this study was able to prevent tumour appearance in an experimental DMH-induced colon cancer model. Fil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Leblanc, Jean Guy Joseph. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Perdigon, Gabriela del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; Argentina Fil: Miyoshi, Anderson. Universidade Federal de Minas Gerais; Brasil Fil: Langella, Philippe. Institut National de la Recherche Agronomique; Francia Fil: Azevedo, Vaso. Universidade Federal de Minas Gerais; Brasil Fil: Sesma, Fernando Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina

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. Fil: de Moreno, Maria Alejandra. Université de Moncton; Canadá. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Matar, Chantal. Université de Moncton; Canadá Fil: Thériault, Catherine. Université de Moncton; Canadá Fil: Perdigon, Gabriela del Valle. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina