The role of microbiota and immunobiotics in granulopoiesis of immunocompromised hosts

The number of granulocytes is maintained by a regulated balance between granulopoiesis in the bone marrow and clearance and destruction in peripheral tissues. Granulopoiesis plays a fundamental role in the innate immune response. Therefore, factors affecting the normal granulopoiesis lead to alterations in innate defenses and reduce the resistance against infections. In this study, we give a description on recent advances regarding the molecular and cellular events that regulate steady-state and emergency granulopoiesis, which are crucial processes for the generation of protective innate immune responses. Particular attention will be given to emergency granulopoiesis alterations in immunosuppression states caused by malnutrition and chemotherapy. The role of microbiota in maintaining a steady-state granulopoiesis and the immunological mechanisms involved are also discussed. Moreover, we describe the findings of our laboratory demonstrating that the dietary supplementation with immunobiotics is an interesting alternative to improve steady-state and emergency granulopoiesis, the respiratory innate immune response, and the resistance against respiratory pathogens in immunocompromised hosts.Fil: Salva, Maria Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; ArgentinaFil: Alvarez, Gladis Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentin

Are the immunomodulatory properties of Lactobacillus rhamnosus CRL1505 peptidoglycan common for all Lactobacilli during respiratory infection in malnourished mice?

Previously, we reported that Lactobacillus rhamnosus CRL1505 peptidoglycan (PG05) improves the innate immune response in immunocompromised-malnourished mice after Streptococcus pneumoniae infection. This study extends those previous findings by demonstrating that the dietary recovery of malnourished mice with nasal administration of PG05 improves not only the innate immune response but the respiratory and systemic adaptive humoral response as well. PG05 enhanced the Th2 response, the recovery of B cells, and the concentration and opsonophagocytic activity of anti-pneumococcal antibodies. In addition, by performing comparative studies with the peptidoglycans from lactobacilli of the same species (L. rhamnosus CRL534) or with similar immunomodulatory properties (L. plantarum CRL1506), we demonstrated here that PG05 has unique immunomodulatory properties that cannot be extended to peptidoglycans from other probiotic strains. However, the knowledge of the molecular characteristics of PG05 is indispensable to understand immunomodulatory abilities of L. rhamnosus CRL1505.Fil: Kolling, Yanina Noralí. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Salva, Maria Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Alvarez, Gladis Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentin

Respiratory antiviral immunity and immunobiotics: Beneficial effects on inflammation-coagulation interaction during influenza virus infection

Influenza virus (IFV) is a major respiratory pathogen of global importance, and the cause of a high degree of morbidity and mortality, especially in high-risk populations such as infants, elderly, and immunocompromised hosts. Given its high capacity to change antigenically, acquired immunity is often not effective to limit IFV infection and therefore vaccination must be constantly redesigned to achieve effective protection. Improvement of respiratory and systemic innate immune mechanisms has been proposed to reduce the incidence and severity of IFV disease. In the last decade, several research works have demonstrated that microbes with the capacity to modulate the mucosal immune system (immunobiotics) are a potential alternative to beneficially modulate the outcome of IFV infection. This review provides an update of the current status on the modulation of respiratory immunity by orally and nasally administered immunobiotics, and their beneficial impact on IFV clearance and inflammatory-mediated lung tissue damage. In particular, we describe the research of our group that investigated the influence of immunobiotics on inflammation-coagulation interactions during IFV infection. Studies have clearly demonstrated that hostile inflammation is accompanied by dysfunctional coagulation in respiratory IFV disease, and our investigations have proved that some immunobiotic strains are able to reduce viral disease severity through their capacity to modulate the immune-coagulative responses in the respiratory tract.Fil: Zelaya, María Hortensia del Rosario. Grupo de Investigación de Inmunobioticos; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Aplicada; ArgentinaFil: Alvarez, Gladis Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina. Grupo de Investigación de Inmunobioticos; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Aplicada; ArgentinaFil: Kitazawa, Haruki. Tohoku University; JapónFil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina. Grupo de Investigación de Inmunobioticos; Argentin

Draft genome sequence of Lactobacillus plantarum CRL1506, an immunomodulatory strain isolated from goat milk

This report describes a draft genome sequence of Lactobacillus plantarum CRL1506, a probiotic strain with immunomodulatory properties isolated from goat milk. The reads generated by a whole-genome shotgun (WGS) strategy on an Illumina MiSeq sequencer were assembled into contigs with a total size of 3,228,096 bp. The draft genome sequence of L. plantarum CRL1506 will be useful for further studies of specific genetic features of this strain and for understanding the mechanisms of its immunobiotic properties.Fil: Saavedra, Maria Lucila. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; ArgentinaFil: Hebert, Elvira Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; ArgentinaFil: Albarracín, Leonardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina. Tohoku University; JapónFil: Salva, Maria Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; ArgentinaFil: Alvarez, Gladis Susana. 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: Kitazawa, Haruki. Tohoku University; JapónFil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina. Tohoku University; Japó

The role of immunobiotics and postbiotics in the recovery of immune cell populations from respiratory mucosa of malnourished hosts: effect on the resistance against respiratory infections

Malnutrition is associated with a state of secondary immunodeficiency, which is characterized by a worsening of the immune response against infectious agents. Despite important advances in vaccines and antibiotic therapies, the respiratory infections are among the leading causes of increased morbidity and mortality, especially in immunosuppressed hosts. In this review, we examine the interactions between immunobiotics-postbiotics and the immune cell populations of the respiratory mucosa. In addition, we discuss how this cross talk affects the maintenance of a normal generation of immune cells, that is crucial for the establishment of protective innate and adaptive immune responses. Particular attention will be given to the alterations in the development of phagocytic cells, T and B lymphocytes in bone marrow, spleen and thymus in immunosuppression state by protein deprivation. Furthermore, we describe our research that demonstrated that the effectiveness of immunobiotics nasal administration in accelerating the recovery of the respiratory immune response in malnourished hosts. Finally, we propose the peptidoglycan from the immunobiotic Lactobacillus rhamnosus CRL1505 as the key cellular component for the effects on mucosal immunity, which are unique and cannot be extrapolated to other L. rhamnosus or probiotic strains. In this way, we provide the scientific bases for its application as a mucosal adjuvant in health plans, mainly aimed to improve the immune response of immunocompromised hosts. The search for safe vaccine adjuvants that increase their effectiveness at the mucosal level is a problem of great scientific relevance today.Fil: Salva, Maria Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Kolling, Yanina Noralí. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Ivir, Héctor Maximiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Gutiérrez, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Alvarez, Gladis Susana. 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; Argentin

Orally administered Lactobacillus rhamnosus modulates the respiratory immune response triggered by the viral pathogen-associated molecular pattern poly(I:C)

Some studies have shown that probiotics, including Lactobacillus rhamnosus CRL1505, had the potential to beneficially modulate the outcome of certain bacterial and viral respiratory infections. However, these studies did not determine the mechanism(s) by which probiotics contribute to host defense against respiratory viruses. In this work we demonstrated that orally administered Lactobacillus rhamnosus CRL1505 (Lr1505) was able to increase the levels of IFN-γ, IL-10 and IL-6 in the respiratory tract and the number of lung CD3(+)CD4(+)IFN-γ(+) T cells. To mimic the pro-inflammatory and physiopathological consecuences of RNA viral infections in the lung, we used an experimental model of lung inflammation based on the administration of the artificial viral pathogen-associated molecular pattern poly(I:C). Nasal administration of poly(I:C) to mice induced a marked impairment of lung function that was accompanied by the production of pro-inflammatory mediators and inflammatory cell recruitment into the airways. The preventive administration of Lr1505 reduced lung injuries and the production of TNF-α, IL-6, IL-8 and MCP-1 in the respiratory tract after the challenge with poly(I:C). Moreover, Lr1505 induced a significant increase in lung and serum IL-10. We also observed that Lr1505 was able to increase respiratory IFN-γ levels and the number of lung CD3(+)CD4(+)IFN-γ(+) T cells after poly(I:C) challenge. Moreover, higher numbers of both CD103(+) and CD11b(high) dendritic cells and increased expression of MHC-II, IL-12 and IFN-γ in these cell populations were found in lungs of Lr1505-treated mice. Therefore, Lr1505 treatment would beneficially regulate the balance between pro-inflammatory mediators and IL-10, allowing an effective inflammatory response against infection and avoiding tissue damage. Results showed that Lr1505 would induce a mobilization of cells from intestine and changes in cytokine profile that would be able to beneficially modulate the respiratory mucosal immunity. Although deeper studies are needed using challenges with respiratory viruses, the results in this study suggest that Lr1505, a potent inducer of antiviral cytokines, may be useful as a prophylactic agent to control respiratory virus infection.Fil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina. Tohoku University. Graduate School of Agricultural Science. Food Immunology Group; JapónFil: Chiba, Eriko. Tohoku University. Graduate School of Agricultural Science. Food Immunology Group; JapónFil: Tomosada, Yohsuke. Tohoku University. Graduate School of Agricultural Science. Food Immunology Group; JapónFil: Salva, Maria Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; ArgentinaFil: Marranzino, Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; ArgentinaFil: Kitazawa, Haruki. Tohoku University. Graduate School of Agricultural Science. Food Immunology Group; JapónFil: Alvarez, Gladis Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentin

Improvement of myelopoiesis in cyclophosphamide-immunosuppressed mice by oral administration of viable or non-viable lactobacillus strains

Myelosuppression is the major dose-limiting toxicity of cancer chemotherapy. There have been many attempts to find new strategies that reduce myelosuppression. The dietary supplementation with lactic acid bacteria (LAB) improved respiratory innate immune response and the resistance against respiratory pathogens in immunosupressed hosts. Although LAB viability is an important factor in achieving optimal protective effects, non-viable LAB are capable of stimulating immunity. In this work, we studied the ability of oral preventive administration of viable and non-viable Lactobacillus rhamnosus CRL1505 or L. plantarum CRL1506 (Lr05, Lr05NV, Lp06V or Lp06NV, respectively) to minimize myelosuppressive and immunosuppressive effects derived from chemotherapy. Cyclophosphamide (Cy) impaired steady-state myelopoiesis in lactobacilli-treated and untreated control mice. Lr05V, Lr05NV and Lp06V treatments were the most effective to induce the early recovery of bone marrow (BM) tissue architecture, leukocytes, myeloid, pool mitotic and post-mitotic, peroxidase positive, and Gr-1Low/High cells in BM. We selected the CRL1505 strain for being the one capable of maintaining its myelopoiesis-enhancing properties in its non-viable form. Although the CRL1505 treatments do not modify the Cy ability to induce apoptosis, both increased the incorporation of BrdU in BM cells. Consequently, Lr05NV and Lr05V treatments were able to promote early recovery of LSK cells (Lin-Sca-1+c-Kit+ cells), multipotent progenitors (Lin-Sca-1+c-Kit+CD34+ cells), and myeloid cells (Gr-1+Ly6G+Ly6C- cells) with respect to the untreated Cy control. In addition, these treatments were able to increase the frequency of IL17A-producing innate lymphoid cells in the intestinal lamina propria (IL-17A+RORγt+CD4-NKp46+ cells) after Cy injection. These results were correlated with an increase in the IL-17A serum levels, a GM-CSF high expression and a CXCL12 lower expression in BM. Therefore, both Lr05V and Lr05NV treatments are able to activate beneficially the IL-17A/GM-CSF axis and accelerate the recovery of Cy-induced immunosuppression by increasing BM myeloid precursors. We demonstrated for the first time the beneficial effect of CRL1505 strain on myelopoiesis affected by a chemotherapeutic drug. Furthermore, Lr05NV could be a good and safe resource for reducing chemotherapy-induced leukopenia. The results are a starting point for future research and open up broad prospects for future applications of the immunobiotics.Fil: Gramajo Lopez, Andres Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Gutiérrez, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Saavedra, Maria Lucila. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Hebert, Elvira Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Alvarez, Gladis Susana. 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: Salva, Maria Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentin

Recent advances and future perspective in microbiota and probiotics

Recent studies have highlighted the critical 1 role of intestinal microbes on health. This special issue covers a range of diverse topics related to microbiota and probiotic in gut health and disease, thus highlighting the potential beneficial role friendly bacteria in human health. We hope the papers published will serve to further highlight the potential application of probiotics for the prevention and treatment of gut diseases, as well as stimulating further research into the cellular and molecular mechanisms of probiotic actions.Fil: Kitazawa, Haruki. Tohoku University. Graduate School of Agricultural Science; JapónFil: Alvarez, Gladis Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia para Lactobacilos (i); ArgentinaFil: Suvorov, Alexander. Institute of Experimental Medicine; RusiaFil: Melnikov, Vyacheslav. International Science and Technology Center; RusiaFil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia para Lactobacilos (i); ArgentinaFil: Sánchez, Borja . Consejo Superior de Investigaciones Cientificas; Españ

Probiotics for everyone! The novel immunobiotic lactobacillus rhamnosus CRL1505 and the beginning of social probiotic programs in Argentina

Lactobacillus rhamnosus CRL1505 (Lr1505) stimulates immune responses in the gut and in the respiratory tract and improves resistance against Salmonella typhimurium and Streptococcus pneumoniae infections in immunocompetent and immunocompromised mice. Considering that respiratory infectious diseases continue to be a major cause of death among preschool children in developing countries, the aim of the present study was to evaluate the effect of Lr1505 on the health of children. A randomized-controlled double-blind clinical trial in 298 healthy children (2-5 years old), attending daycare centers was performed. Yogurt containing Lr1505 was administered to children for 6 months (five times a week). Results were statistically compared with those of children from the same community that received a placebo yogurt (without probiotic). Administration of Lr1505 to young children reduced the incidence of infections: 66% of children in the placebo group presented symptoms of infection while only 34% of cases were detected in the Lr1505 group. Significant differences (P<0.05) were detected in the incidence of intestinal infections, upper respiratory tract infections and angina when placebo and Lr1505 groups were compared. Children fed Lr1505 experienced fewer fevers and needed fewer antibiotics than those receiving the placebo. The protective effect of Lr1505 was associated with increased levels of mucosal IgA antibodies. Lr1505 is a promising resource for the development of prevention strategies against mucosal infections that could be effective tools for medical application. This new probiotic strain has been included into official Nutritional Programs in Argentina and it is given to more than 200 thousand children. This project has encouraged local milk production, thanks to the constant demand of probiotic yogurt containing L. rhamnosus CRL1505 by provincial governments, while incorporating innovation to small and medium enterprises.Fil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; ArgentinaFil: Salva, Maria Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; ArgentinaFil: Nuñez, Martha Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; ArgentinaFil: Corzo, Josefina. Provincia de Tucuman. Sistema Provincial de Salud de Tucuman; ArgentinaFil: Tolaba, René. Universidad Nacional de Tucuman. Facultad de Medicina; Argentina. Provincia de Tucuman. Ministerio de Salud. Sistema Provincial de Salud. Hospital del Ni?o Jesus; ArgentinaFil: Faedda, Julio. Provincia de Tucuman. Ministerio de Salud. Sistema Provincial de Salud. Hospital del Ni?o Jesus; ArgentinaFil: Font, Graciela Maria. 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: Alvarez, Gladis Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina. Universidad Nacional de Tucuman. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Clinica Aplicada. Cátedra de Bioquímica Clinica I; Argentin

Dietary supplementation with lactobacilli improves emergency granulopoiesis in protein-malnourished mice and enhances respiratory innate immune response

This work studied the effect of protein malnutrition on the hemato-immune response to the respiratory challenge with Streptococcus pneumoniae and evaluated whether the dietary recovery with a probiotic strain has a beneficial effect in that response. Three important conclusions can be inferred from the results presented in this work: a) protein-malnutrition significantly impairs the emergency myelopoiesis induced by the generation of the innate immune response against pneumococcal infection; b) repletion of malnourished mice with treatments including nasally or orally administered Lactobacillus rhamnosus CRL1505 are able to significantly accelerate the recovery of granulopoiesis and improve innate immunity and; c) the immunological mechanisms involved in the protective effect of immunobiotics vary according to the route of administration. The study demonstrated that dietary recovery of malnourished mice with oral or nasal administration of L. rhamnosus CRL1505 improves emergency granulopoiesis and that CXCR4/CXCR12 signaling would be involved in this effect. Then, the results summarized here are a starting point for future research and open up broad prospects for future applications of probiotics in the recovery of immunocompromised malnourished hosts.Fil: Herrera, Héctor Matías. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; ArgentinaFil: Salva, Maria Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; ArgentinaFil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; ArgentinaFil: Barbieri, Natalia Paola del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina. Universidad Nacional de Chilecito; ArgentinaFil: Marranzino, Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucuman. Instituto Superior de Investigaciones Biologicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; ArgentinaFil: Alvarez, Gladis Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina. Universidad Nacional de Tucuman. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Clinica Aplicada. Cátedra de Bioquímica Clinica I; Argentin