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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.

Chemotherapy is the most common treatment for breast cancer and its metastasis; however, it affects the patients' quality of life. Previously, it was demonstrated that milk fermented by Lactobacillus casei CRL431 (probiotic fermented milk (PFM)) exerted benefits against breast cancer metastasis by modulating the immune response in a mouse model. The aim of this work was to evaluate PFM administration on the side effects of capecitabine and on its anti-tumour/anti-metastatic effects. In vitro, 4T1 breast cancer cells were treated with capecitabine in the presence of immune cells' conditioned media from mice administered with PFM. Cell viability was evaluated by MTT assay. In vivo, BALB/c mice (healthy, bearing breast cancer or with potential metastasis) were treated or not with capecitabine and administered with PFM. Blood cell counts, intestinal damages, lung histology and serum cytokines were evaluated. Results showed that capecitabine's toxicity on 4T1 cells was improved by the immune cells from mice that received PFM when the lower dose of capecitabine was evaluated. PFM reduced capecitabine side effects in all the mouse models and decreased intestinal mucositis and mortality. PFM administration to mice under chemotherapy maintained the anti-cancer/anti-metastasis effect of capecitabine with similar or decreased values for serum IL-10 and TNF-α and decreased IL-6, a cytokine related to poor prognosis in advanced cancer patients. In addition, PFM by itself reduced metastasis without side effects and improved the host's immune response. PFM has a potential to be administered as an immune adjuvant in patients under chemotherapy without affecting the treatment. KEY POINTS: • Milk fermented by L. casei CRL431 (PFM) diminished capecitabine side effects. • Capecitabine's toxicity on 4T1 cells was improved by the PFM-stimulated immune cells. • PFM maintained anti-cancer/anti-metastasis effect of capecitabine in mouse models. Graphical abstract.

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

Aims: To evaluate a mixture of selected lactic acid bacteria (LAB) (a riboflavin-producer, a folate-producer and an immunomodulatory strain) as co-adjuvant for 5-fluorouracil (5-FU) chemotherapy in cell culture and using a 4T1 cell animal model of breast cancer. Methods and results: The viability of Caco-2 cells exposed to 5-FU and/or LAB was analysed. Mice bearing breast tumour were treated with 5-FU and/or LAB. Tumour growth was measured. Intestinal mucositis (IM) was evaluated in small intestine; haematological parameters and plasma cytokines were determined. The bacterial mixture did not negatively affect the cytotoxic activity of 5-FU on Caco-2 cells. The LAB mixture attenuated the IM and prevented blood cell decreases associated with 5-FU treatment. Mice that received 5-FU and LAB mixture decreased tumour growth and showed modulation of systemic cytokines modified by both tumour growth and 5-FU treatment. The LAB mixture by itself delayed tumour growth. Conclusions: The mixture of selected LAB was able to reduce the side-effects associated with chemotherapy without affecting its primary anti-tumour activity. Significance and Impact of the Study: This bacterial mixture could prevent the interruption of conventional oncologic therapies by reducing undesirable side-effects. In addition, this blend would provide essential nutrients (vitamins) to oncology patients. 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

Breast cancer is one of the leading causes of death worldwide. It is recognised that immune system influences its promotion, progression, and metastasis, as well as their responsiveness to therapies. Previously, it was reported that milk fermented by Lactobacillus casei CRL431 decreased tumour growth and metastasis in a mouse breast cancer model, through the modulation of the host immune response. The aim of the present work was to analyse the systemic immune response induced by the administration of probiotic fermented milk (PFM) at different stages of cancer development, evaluating cytokines produced by splenocytes stimulated in vitro with 4T1 tumour cells, or its conditioned medium (CM). Groups of healthy mice and mice bearing 4T1 tumour or suffering metastasis after tumour surgery were studied. Results showed that at the early stages, PFM maintained pro-inflammatory response associated to the delay or the inhibition of tumour growth. PFM administration to mice bearing tumour maintained an important inflammatory response; however, in contrast to the milk group, this response was regulated to avoid exacerbation of inflammation. In the metastasis model, the benefits of PFM were associated to avoid the immunosuppression associated to high interleukin-10 levels. In conclusion, as cancer cells induce modifications of the immune response to favour their own growth at each stage of cancer development, PFM administration stimulated different profile of cytokines to respond to these modifications and fight against cancer cells. 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; 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

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

Probiotics represents an alternative to replace antibiotics as growth promoters in animal feed and are able to control enteric bacterial diseases and to improve gut immunity. Saccharomyces cerevisiae RC016 showed previously inhibition/ coagregation of pathogens) and mycotoxins adsorbent ability (aflatoxin B1, ochratoxin A and zearalenone). The aim of this work was to evaluate beneficial properties of S. cerevisiae RC016 in a non-inflammatory in vivo model in weaned piglets and in an intestinal inflammation ex vivo model induced by the mycotoxin deoxynivalenol (DON). Secretory immunoglobulin A (s-IgA) levels, intestinal cytokines, goblet cells and production parameters were evaluated in a pig model. For the in vivo assays, twelve pigs were weaned at 21 days and assigned to two groups: Control (n=6) and Yeast (n=6). Animals received yeast strain for three weeks. After 22 days the small intestine was recovered for determination of goblet cells and s-IgA. For the ex vivo assay, jejunal explants were obtained from 5 weeks old crossbred piglets and treated as follow: (1) control; (2) treated for 3 h with 10 μM DON used as an inflammatory stressor; (3) incubated with 107 cfu/ml yeast strain; (4) pre-incubated 1 h with 107 cfu/ml yeast strain and then treated for 3 h with 10 μM DON. CCL20, interleukin (IL)-1β, IL-8 and IL-22 gene expression was determined by qPCR. Oral administration of S. cerevisiae RC016 increased s-IgA, the number of goblet cells in small intestine and all the growth parameters measured. In the ex vivo model, the cytokine profile studied showed a potential anti-inflammatory effect of the administration of the yeast. In conclusion, S. cerevisiae RC016 is a promising candidate for feed additives formulation to improve animal growth and gut immune system. This yeast strain could be able to improve the gut health through counteracting the weaning-associated intestinal inflammation in piglets. Fil: García, Gisela Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Universidad Nacional de Río Cuarto; Argentina Fil: Dogi, Cecilia Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Universidad Nacional de Río Cuarto; Argentina Fil: Poloni, Valeria Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Universidad Nacional de Río Cuarto; Argentina Fil: Fochesato, Analía Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Universidad Nacional de Río Cuarto; 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: Cossalter, Anne Marie. Institut National de la Recherche Agronomique; Francia. Université de Toulouse; Francia Fil: Payros, Delphine. Institut National de la Recherche Agronomique; Francia. Université de Toulouse; Francia Fil: Oswald, Isabelle P.. Institut National de la Recherche Agronomique; Francia. Université de Toulouse; Francia Fil: Cavaglieri, Lilia Reneé. Universidad Nacional de Río Cuarto; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; 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.

International audience; Maternal immune activation (MIA) and poor maternal nutritional habits are risk factors for the occurrence of neurodevelopmental disorders (NDD). Human studies show the deleterious impact of prenatal inflammation and low n-3 polyunsaturated fatty acid (PUFA) intake on neurodevelopment with long-lasting consequences on behavior. However, the mechanisms linking maternal nutritional status to MIA are still unclear, despite their relevance to the etiology of NDD. We demonstrate here that low maternal n-3 PUFA intake worsens MIA-induced early gut dysfunction, including modification of gut microbiota composition and higher local inflammatory reactivity. These deficits correlate with alterations of microglia-neuron crosstalk pathways and have long-lasting effects, both at transcriptional and behavioral levels. This work highlights the perinatal period as a critical time window, especially regarding the role of the gut-brain axis in neurodevelopment, elucidating the link between MIA, poor nutritional habits, and NDD. Fig. 1 EFFECT OF N-3 PUFA DEFICIENCY ON MIA-INDUCED BEHAVIORAL DEFICITS IN NEONATES AND IN ADULT OFFSPRING.: All graphs show Means ± SEM. a Experimental setup. b Average time spent by pups to achieve the Fox battery tests (negative geotaxis and righting reflex; 3 trials per day from PND4 to PND6). N = 14-19. Two-way ANOVA: MIA effect, F(1,62) = 11.67, p = 0.0011. c Average vocalization time (15-min sessions at PND7-8). N = 14-19. Kruskal-Wallis test followed by Mann-Whitney comparison; n-3 sufficient-Saline vs n-3 sufficient-LPS, **p

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

Aim: To evaluate two folate-producing strains, Streptococcus (Strep.) thermophilus CRL 808 and Strep. thermophilus CRL 415, against chemically induced mucositis in mice. Methods and Results: In vitro assays with Caco-2 cells were performed to evaluate the effect of the bacteria in the presence of 5-fluorouracil (5-FU). For in vivo studies, mice were daily injected with 5-FU to induce intestinal mucositis (IM) and orally administered with folate-producing strains during 6 days. Clinical symptoms, histological parameters and cytokine profiles were assessed. The results showed that Strep. thermophilus CRL 808 increased the cytotoxicity of 5-FU against Caco-2 cells. Administration of this strain in mice with chemically induced IM resulted in a reduction in diarrhoea score and restoration of the intestinal architecture. Cytokine analysis showed that the anti-inflammatory effect by the bacterium is not associated with an immune mechanism. Regarding Strep. thermophilus CRL 415, no improvements were observed in any of the parameters evaluated. Conclusion: The administration of the folate-producing Strep. thermophilus CRL 808 has the potential to prevent IM induced by 5-FU in mice. Significance and Impact of the Study: Folate-producing LAB could be used in chemotherapy patients to reduce the symptoms of IM, improve their nutritional status and increase the effectiveness of 5-FU. 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

Aim: To assess the anti-inflammatory effect associated with individual probiotic suspensions of riboflavin-producing lactic acid bacteria (LAB) in a colitis murine model. Methods and Results: Mice intrarectally inoculated with trinitrobenzene sulfonic acid (TNBS) were orally administered with individual suspensions of riboflavin-producing strains: Lactobacillus (Lact.) plantarum CRL2130, Lact. paracasei CRL76, Lact. bulgaricus CRL871 and Streptococcus thermophilus CRL803; and a nonriboflavin-producing strain or commercial riboflavin. The extent of colonic damage and inflammation and microbial translocation to liver were evaluated. iNOs enzyme was analysed in the intestinal tissues and cytokine concentrations in the intestinal fluids. Animals given either one of the four riboflavin-producing strains showed lower macroscopic and histologic damage scores, lower microbial translocation to liver, significant decreases of iNOs+ cells in their large intestines and decreased proinflammatory cytokines, compared with mice without treatment. The administration of pure riboflavin showed similar benefits. Lact. paracasei CRL76 accompanied its anti-inflammatory effect with increased IL-10 levels demonstrating other beneficial properties in addition to the vitamin production. Conclusion: Administration of riboflavin-producing strains prevented the intestinal damage induced by TNBS in mice. Significance and Impact of the Study: Riboflavin-producing phenotype in LAB represents a potent tool to select them for preventing/treating IBD. Fil: Levit, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina Fil: Savoy, Graciela. 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; 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: 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 idiopathic diseases of the gastrointestinal tract characterised by recurrent inflammation that require lifelong treatments. It has been shown that certain strains of lactic acid bacteria (LAB) can produce specific health-promoting compounds in foods or in the gastrointestinal tract that can in turn prevent and/or treat IBD. This study was designed to evaluate the possible therapeutic potential of soymilk fermented by the riboflavin-producing strain Lactobacillus plantarum CRL 2130 in a trinitrobenzene sulfonic induced colitis mouse model. Mice that received soymilk fermented by L. plantarum CRL 2130 showed a decrease in weight loss, lower damage scores in their large intestines, lower microbial translocation to liver and decreased cytokines levels in their intestinal fluids compared to animals that received unfermented soymilk or soymilk fermented by a nonriboflavin- producing L. plantarum strain. This is the first report that demonstrates that a riboflavin-producing LAB was able to prevent experimental colitis in a murine model. 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

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

Lactobacillus rhamnosus RC007 is a potential probiotic bacterium that can exert beneficial effects as supplement for animal feed, by improving the immune status in healthy host, and by providing therapeutic benefits to infected/inflamed animals. The aim of the present work was to evaluate in vivo the beneficial properties of L. rhamnosus RC007, intended for animal feed, when administered to healthy and trinitro-benzene-sulfonic-acid (TNBS) colitis induced BALB/c mice. The administration of L. rhamnosus RC007 to healthy mice during 10 days increased the phagocytic activity of peritoneal macrophages and the number of immunoglobulin A+ cells in the lamina proper of the small intestine. Significant increases of monocyte chemotactic protein 1, interleukin (IL)-10 and tumour necrosis factor alpha (TNF-α) concentrations, and in the ratio between anti- and pro-inflammatory cytokines (IL-10/TNF-α) were observed in intestinal fluids after administration of bacteria. In the inflammation model, less body weight loss, macroscopic and histological damages in the large intestine were accompanied by increased IL-10/TNF-α ratio in the intestinal fluids of mice from the L. rhamnosus-TNBS group when compared to the TNBS group. In a healthy host, the oral administration of L. rhamnosus RC007 kept the gut immune system stimulated allowing a faster response to noxious stimulus. Mice that received L. rhamnosus RC007 also decreased the severity of the intestinal inflammation. Fil: Dogi, Cecilia Ana. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Microbiología e Inmunología; Argentina Fil: García, Gisela Romina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Microbiología e Inmunología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; 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: Greco, Cecilia Rosa. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Microbiología e Inmunología; Argentina Fil: Cavaglieri, Lilia Reneé. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Microbiología e Inmunología. Cátedra de Micología; Argentina

Aims: To evaluate the beneficial properties of a potentially probiotic yoghurt obtained by the fermentation of two selected anti-inflammatory bacterial strains using in vivo mouse models of intestinal inflammation and colon carcinogenesis. Methods and Results: Yoghurt was administered to mice suffering chemically induced intestinal inflammation or colon carcinogenesis. It was shown that this novel yoghurt was able to prevent local inflammation in the intestines of mice through a regulation of the immune response, prevent macroscopic and histological damages, and prevent colon carcinogenesis through an anti-inflammatory response. Conclusions: The developed yoghurt showed in vivo anti-inflammatory properties by modulation of the host immune response for the prevention of colon inflammation and carcinogenesis. Significance and Impact of the Study: This new yoghurt could thus be considered a probiotic food and be useful as a complement to current treatment protocols for inflammatory bowel diseases and colon cancer, a first since there are no current functional foods specifically oriented for these patients. 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: Leblanc, Jean Guy Joseph. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. 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 disease (IBD), including Crohn's disease and ulcerative colitis, are important problems in industrialized countries. The complete aetiology of both diseases is still unknown but likely involves genetic, environmental and immunological factors. The aim of this work is to study the anti-inflammatory mechanisms reported for yoghurt in a colon cancer model in order to evaluate its usefulness in the treatment of intestinal inflammation such as Crohn's disease. A trinitrobenzenesulfonic acid (TNBS)-induced colitis model was used. The influence of yoghurt feeding was studied before and after TNBS inoculation. The effect on the intestinal microbiota and on the host immune response was evaluated. IgA-producing cells and cells positive for specific cytokines (IL-12, IL-17, IFNγ and IL-10) were analyzed. Yoghurt administration diminished the severity of inflammation in the TNBS-inoculated mice. This effect occurred mainly through IL-10, which was increased in the intestinal tissues throughout the study, and by the decrease observed in IL-17 and IL-12 levels. In addition to this immunomodulatory capacity, another mechanism by which yoghurt could exert the anti-inflammatory activity observed in our model would be through beneficial changes in the intestinal microbiota (increases in the bifidobacteria and lactobacilli populations). These changes in the intestinal microbiota could also be considered one of the causes of the intestinal inflammation reduction. These results show that yoghurt administration modulated the immune response, inducing down regulation of the inflammatory cytokines produced by the immune cells involved in the inflammatory process. The protective effect. Fil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Chaves, Analia Silvina. 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: 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

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

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

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

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

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

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.

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

Administration of kefir and a kefir cell-free fraction (KF) to mice injected with breast tumor cells produced, locally in the mammary gland, different profiles of cells secreting cytokines. Here, the immune cell populations in mammary glands affected by the cyclic consumption of kefir or KF for 2 or 7 d were evaluated using a breast tumor model. Apoptosis was also assayed as another mechanism involved in tumor growth delay. The rate development of tumor cells, IgA(+) cells, and CD4+ and CD8+ T lymphocytes was monitored in mammary gland tissues. The number of Bcl-2(+) cells in the mammary gland was compared with the apoptosis observed in the tumor. Two-day cyclical administration of both products delayed tumor growth and increased the number of IgA(+) cells in the mammary gland. Changes in the balance between CD4+ and CD8+ cells in the mammary gland were observed in mice from the group fed KF cyclically for 2 d, such that the number of CD4+ cells increased when the number of CD8+ cells remained constant. Mice that received 2-d cyclic administration of KF showed significant increases in the number of apoptotic cells and decreases in Bcl-2(+) cells in the mammary gland, compared with the tumor control group. The present study allows a better understanding of the mechanisms (immune and nonimmune) involved in the antitumor effect observed in mice administered kefir or KF. The importance of nonmicrobial components released during milk fermentation to obtain the beneficial antitumor effects is also reported. Fil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Université de Moncton; Canadá. Universidad Nacional de Tucumán; Argentina Fil: Matar, Chantal. Université de Moncton; Canadá Fil: Farnworth, Edward. Food Research and Development Centre. Agriculture and Agri-Food; 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

The aim of this work was to study the long-lasting consequences of different weaning age on physiological, immunological and microbiological parameters of weaned piglets. Piglets were weaned at 14 days (14W) or 21 days (21W). Blood samples were taken for IgG and cortisol determination on preweaning day and at 4; 20 and 40 post-weaning days. Three animals of each group were sacrificed. Small intestines for morphometric studies and secretory-IgA determination in fluid were taken. The cecum was obtained for enterobacteria, lactobacilli and total anaerobes enumeration. A significant decrease in piglet's plasma IgG concentrations was observed immediately after weaning and no differences were found between 14W and 21W. An increase in intestinal S-IgA was observed according to piglet's age. This increase was significantly higher in piglets 14W compared to piglets 21W. Animals from 14W group showed a decrease in villus length and in the number of goblet cells and intraepithelial lymphocytes. Other parameters were not affected by the weaning age. A short-term increase in cortisol was observed after weaning in both experimental groups. Enterobacteria decreased significantly after weaning in both groups, reaching values of weaning after 40 days. Lactobacilli counts decreased in both groups after weaning; however their counts were always higher than those obtained for enterobacteria. No differences were observed between 14W and 21W with regards to counts of anaerobes. The shortening of breast feeding time would favor an early synthesis of intestinal S-IgA after weaning. The changes observed in the microbiota could decrease postweaning enteric infections. However, early weaning induced negative effects on the cells of gut innate immunity and villi atrophy. This work provides knowledge about advantages and disadvantages at different weaning and long-lasting consequences on pig health. It is critical that swine producers become aware of the biological impacts of weaning age, so as to be able to decide the appropriate management strategies according to their facilities and rearing environment. Fil: García, Gisela Romina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Microbiología e Inmunología; Argentina Fil: Dogi, Cecilia Ana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Microbiología e Inmunología; Argentina Fil: Ashworth, Guillermo Edgardo. Universidad Nacional de Río Cuarto; Argentina Fil: Berardo, D.. Universidad Nacional de Río Cuarto; Argentina Fil: Godoy, G.. Universidad Nacional de Río Cuarto; Argentina Fil: Cavaglieri, Lilia Reneé. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Microbiología e Inmunología; 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: Greco, Cecilia Rosa. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Microbiología e Inmunología; 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

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

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

Lactic acid bacteria (LAB) found in numerous fermented products can interact with the gut associated lymphoid tissue increasing antibody (principally secretory IgA) production. IgA secreting cells can repopulate not only the lamina propria but also they can go to other distant sites such as bronchus, urogenital tract and mammary glands a phenomenon known as the IgA cycle. Later studies have shown that both B cells of other isotypes and T cells from Peyer's patches also exhibit gut-seeking properties. The aim of this study was to study the effect of different feeding periods of L. casei CRL 431 on the interaction with the immune cells in Peyer's patches studying the migration of not only the IgA+ cells, but also other immune cells (T lymphocytes) to other mucosal sites such as bronchus and mammary glands. BALB/c mice were fed with L. casei CRL 431 during 2, 5 or 7 days. At the end of the feeding period, the mice were killed and the small intestine, the lung and the mammary glands were removed. IgA+ cells and CD4+ and CD8+ T lymphocytes were counted in tissue slices using direct immunofluorescence. IgA+ cells increased in the intestine samples taken after 7 days of LAB feeding. In mammary gland and lung tissues, IgA+ cells increased after five days of feeding. CD4+ and CD8+ T lymphocytes were not able to migrate to sites distant from the intestine and their number did not increase in the lamina propria of the small intestine. L. casei CRL 431 was able to stimulate the IgA cycle without proliferation of T population. These results allow us to suggest that this LAB could be used as oral adjuvant to protect mucosal surfaces from intestinal and respiratory diseases, and would also be useful as an adjuvant to protect against mammary glands pathologies such as cancer.

Lactic acid bacteria (LAB) are the most commonly used microorganisms in probiotic products and it is known that these LAB enhanced the immune response and increase resistance to neoplasia and infections. In previous studies using an experimental model of BALB/c mice it was demonstrated that a cyclical diet of yoghurt given to animals previously injected with the carcinogen 1,2 dimethylhydrazine (DMH) inhibited the development of colorectal carcinoma. The animals showed an inflammatory response prior to the development of the tumour, which was diminished with the yoghurt feeding. We examined the immunoregulatory and antiinflammatory mechanisms involved in the inhibition of tumour growth by yoghurt and compared with the mechanisms of a non-steroidal antiinflammatory drug (Indomethacin). Five experimental groups (BALB/c mice) were used in this study: 1) DMH group, injected with 1,2 dimethylhydrazine weekly for 10 weeks. 2) DMH-yoghurt group, yoghurt was supplemented 10 days followed by inoculation with DMH. After tumour induction yoghurt was given every 10 days for six months. 3) Only yoghurt given during six months following the same schedule (yoghurt control. 4) DMH-indomethacin group. After tumour induction, animals were treated with indomethacin, injected cyclically. 5) Non-treatment control group fed with a conventional balanced diet. We studied IgA secreting cells and CD4+ and CD8+ T cells in the large intestine of mice fed long term with yoghurt and others treated with indomethacin. TNFα, INFγ cytokines, Bcl2 protein and iNOS enzyme production was also measured We observed an increase in the number of IgA-secreting cells but not in the CD4+ and CD8+ cells in the mice fed long term with yoghurt. Indomethacin treated mice showed high values of all these cellular populations. Mice injected with indomethacin did not show increased levels of the proinflammatory cytokine TNFα and INFγ. These cytokines were increased in DMH and DMH plus yoghurt groups. iNOS enzyme determinations were increased in DMH and DMH plus indomethacin group. These results coincided with the inflammatory response observed in the histological findings. Bcl-2 protein was increased in mice fed long term with yoghurt. We suggest that the immune mechanisms by which yoghurt operates would be different to those induced with the antiinflammatory drug indomethacin. Yoghurt activated the production of cytokines that could exert a regulation of the immune response by apoptosis induced by TNFα. We conclude that yoghurt down modulate the immune response and exert its antitumour activity by its antiinflammatory activity, a mechanism that is different with that of the antiinflammatory indomethacin.

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

Probiotic microorganisms and fermented foods containing lactic acid bacteria have been growing in popularity due to increasing numbers of studies proving that certain strains present health promoting properties, among them the prevention or treatment in the early stages of some types of cancers. There are many reports about the anticarcinogenic effect ofprobiotic strains and fermented products against intestinal and non intestinal tumors. Different mechanisms of action can be involved in these beneficial effects, being the modulation of the host?s immunity one of the most important properties reported using in vitro assays and also in animal models. However, there are few human trials in which the application of probiotics as biotherapeutics against cancer were tested. These assays are very important before the medical community can accept the addition of probiotic or fermented milks as supplements for cancer patients. This review summarizes some of the relevant research with probiotics and fermented products containing lactic acid bacteria in cancer prevention and / or treatment with emphasis on the possible mechanisms involved. Colon cancer is one of the types of cancer for which there are more researches and will be discussed separately from the non intestinal tumours. Fil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia para Lactobacilos (i); Argentina