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

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

Probiotics as protective agents against Enterobacteria

Salmonella is one of the major causative agents of foodborne diseases, morbidity and mortality worldwide. Salmonella enterica serovar typhimurium(S. typhimurium) produces in mice an infection with similar pathogenesis and clinical manifestations than S. typhiin humans. Probiotics influence the innate and adaptive immunity and the activity of the intestinal microbiota. This knowledge allowed us to propose the use of probiotic bacteria against Salmonella infection. On this topic, the mechanisms mediating this protection are not yet established. We determine the effect of the oral administration of probiotic bacterium L. casei CRL-431 on the biological and immune mechanisms involved in the prevention and treatment of the S. Typhimurium infection, using BALB/c mice. Oral administration of probiotic to healthy mice, induced activation of gut immune cells in a regulated state. The continuous L. casei CRL-431 administration (previous and post-infection) protected mice challenged with S. Typhimurium. The mechanisms involved were: a) The modulation of innate immune response by increased TLR expression on epithelial and immune cells. b) Epithelial cell activation, evidenced by increases in secretion of IL-6 and MCP-1. c) Increased number of macrophages, dendritic cells and IgA (+) cells in lamina propria of the small intestine, and increased secretion of total S-IgA. d)Reduction of inflammation, with reduced TNF-alpha levels and myeloperoxidase activity, less PMN infiltration in lamina propria and regulation by IL-10. e)Increased phagocytic activity in macrophage isolated from Peyer’s patches, spleen and peritoneum, correlated with an increase of IFNgamma. The results showed that L. casei CRL-431 induces biological and immune mechanisms, which confer resistance to S. typhimuriuminfection, showing lesser severity of the infection. The safety of continuous administration of this probiotc strain, allows us to suggest its use as an adjuvant of the mucosal immune system in the prevention, and during Salmonella infection.Fil: Perdigon, Gabriela del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Tucumán. Centro de Referencia Para Lactobacilos (i); Argentina;Fil: Castillo, Natalia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Tucumán. Planta Piloto de Procesos Industriales Microbiológicos (i); Argentina;Fil: Maldonado Galdeano, María Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Tucumán. Centro de Referencia Para Lactobacilos (i); Argentina;Fil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Tucumán. Centro de Referencia Para Lactobacilos (i); Argentina

Modification in the diet can induce beneficial effects against breast cancer

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

Improved response of intestinal epithelial cells against Salmonella enterica serovar Typhimurium infection in mice fed with Lactobacillus casei CRL 431.

Lactobacillus casei CRL431 (Lc) protected against Salmonella enterica serovar Typhimurium (ST) infection modulating the immune cells in a mouse model. Intestinal epithelial cells (IECs) participate in the early response against ST. Our aim was to evaluate IEC response in mice received Lc and infected with ST, and using vitro assays. Lc7d-group received Lc during 7days (d), was challenged with ST and continued Lc administration 10d post-infection (PI). IECs were isolated from these mice and from untreated (UC) and infected (IC) controls. IECs from UC were also challenged with ST or Lc for in vitro tests. IL-6 and MCP-1 increased significantly in the IEC culture supernatants from Lc7d-group compared to UC (before infection) and to IC (24h PI). IC increased the release of IL-6 from IECs, 7 and 10d PI. In vitro, IECs challenged with Lc released higher levels of IL-6 than IECs challenged with ST. These results showed another font of IL-6, necessary for B-cell clonal expansion and specific anti-ST IgA-s production, both increased in mice from Lc7d-group. The participation of cells from innate response, such as macrophages, in Lc stimulation agrees with the results obtained for MCP-1. Instead, ST infection increased neutrophils influx and mieloperoxidase activity in the intestine, which decreased in Lc7d-group. Lc administration induced an earlier response against ST, increased IL-6 release and MCP-1 secretion for macrophage recruitment and limited the influx of neutrophils. Lc stimulates not only the intestinal immune cells, but also IECs, first step of this infection.Fil: Castillo, Natalia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Maldonado Galdeano, María Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: 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. Instituto de Microbiología. Cátedra de Inmunología; ArgentinaFil: Perdigon, Gabriela del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina15th International Congress of Mucosal ImmunologyParisFranciaUniversidad de París Descarte

Effect of riboflavin-producing bacteria against chemically induced colitis in mice

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

Recent update on lactic acid bacteria producing riboflavin and folates: application for food fortification and treatment of intestinal inflammation

Lactic acid bacteria (LAB), widely used as starter cultures for the fermentation of a large variety of food, can improve the safety, shelf life, nutritional value and overall quality of the fermented products. In this regard, the selection of strains delivering health-promoting compounds is now the main objective of many researchers. Although most LAB are auxotrophic for several vitamins, it is known that certain strains have the capability to synthesize B-group vitamins. This is an important property since humans cannot synthesize most vitamins, and these could be obtained by consuming LAB fermented foods. This review discusses the use of LAB as an alternative to fortification by the chemical synthesis to increase riboflavin and folate concentrations in food. Moreover, it provides an overview of the recent applications of vitamin-producing LAB with anti-inflammatory/antioxidant activities against gastrointestinal tract inflammation. This review shows the potential uses of riboflavin and folates producing LAB for the biofortification of food, as therapeutics against intestinal pathologies and to complement anti-inflammatory/anti-neoplastic treatments.Fil: Levit, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: 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; ArgentinaFil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Leblanc, Jean Guy Joseph. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentin

Evaluation of vitamin-producing and immunomodulatory lactic acid bacteria as a potential co-adjuvant for cancer therapy in a mouse model

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; ArgentinaFil: 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; ArgentinaFil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Leblanc, Jean Guy Joseph. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentin

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

Objectives: Parkinson's disease (PD) is a neurodegenerative process that affects the motor function and involves an inflammatory response and B vitamin deficiencies. The aim of this study was to evaluate the effect of B-group vitamin-producing and immunomodulatory lactic acid bacteria (LAB) in a murine model of PD. Methods: The effect of Lactobacillus plantarum CRL 2130 (a riboflavin producer), Streptococcus thermophilus CRL 807 (an immunomodulatory strain), and Streptococcus thermophilus CRL 808 (a folate producer) were evaluated individually and as a mixture in mice injected with 1-methyl-4-fenil-1,2,3,6-tetrahidropiridina. Motor capacity, tyrosine hydrolase in the brain, and cytokine concentrations in serum and brain tissues were evaluated in 1-methyl-4-fenil-1,2,3,6-tetrahidropiridina-treated mice after bacterial supplementation. Results: The mice receiving the selected LAB showed significantly improved motor skills compared with those that did not receive bacterial supplementation. When given the mixture of all 3 strains together, the animals had higher brain tyrosine hydrolase-positive cell counts, decreased inflammatory cytokines interleukin 6 and tumor necrosis factor alpha in serum, and increased antiinflammatory cytokine interleukin 10 in serum and brain tissues compared with animals that did not receive LAB supplementation. Conclusions: The results showed the potential of a selected LAB mixture to improve motor behavior and neuroinflammation in PD. This probiotic mixture could be used as an adjunct treatment in the control of PD.Fil: Pérez Visñuk, Daiana Emilce. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: 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; ArgentinaFil: Leblanc, Jean Guy Joseph. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentin

Non-specific vaccination exerts anti-tumor effect through CD11c (+) cells stimulation in a breast cancer model

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

Current review of genetically modified lactic acid bacteria for the prevention and treatment of colitis using murine models

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; ArgentinaFil: del Carmen, Silvina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Chatel, Jean Marc. Institut National de la Recherche Agronomique; FranciaFil: Miyoshi, Anderson. Universidade Federal do Minas Gerais; BrasilFil: Azevedo, Vasco. Universidade Federal do Minas Gerais; BrasilFil: Langella, Philippe. Institut National de la Recherche Agronomique; FranciaFil: Bermudez Humaran, Luis G.. Institut National de la Recherche Agronomique; FranciaFil: Leblanc, Jean Guy Joseph. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentin