Evaluation of Rouxiella badensis Subsp Acadiensis (Canan SV-53) as a Potential Probiotic Bacterium.

The advent of omic platforms revealed the significant benefits of probiotics in the prevention of many infectious diseases. This led to a growing interest in novel strains of probiotics endowed with health characteristics related to microbiome and immune modulation. Therefore, autochthonous bacteria in plant ecosystems might offer a good source for novel next-generation probiotics. The main objective of this study was to analyze the effect of Rouxiella badensis acadiensis Canan (R. acadiensis) a bacterium isolated from the blueberry biota, on the mammalian intestinal ecosystem and its potential as a probiotic microorganism. R. acadiensis, reinforced the intestinal epithelial barrier avoiding bacterial translocation from the gut to deep tissues, even after feeding BALB/c mice for a prolonged period of time. Moreover, diet supplementation with R. acadiensis led to increases in the number of Paneth cells, well as an increase in the antimicrobial peptide α defensin. The anti-bacterial effect of R. acadiensis against Staphylococcus aureus and Salmonella enterica serovar Typhimurium was also reported. Importantly, R. acadiensis-fed animals showed better survival in an in vivo Salmonella enterica serovar Typhimurium challenge compared with those that received a conventional diet. These results demonstrated that R. acadiensis possesses characteristics of a probiotic strain by contributing to the reinforcement and maintenance of intestinal homeostasis.

Thymus, undernutrition, and infection: Approaching cellular and molecular interactions.

Undernutrition remains a major issue in global health. Low protein-energy consumption, results in stunting, wasting and/or underweight, three deleterious forms of malnutrition that affect roughly 200 million children under the age of five years. Undernutrition compromises the immune system with the generation of various degrees of immunodeficiency, which in turn, renders undernourished individuals more sensitive to acute infections. The severity of various infectious diseases including visceral leishmaniasis (VL), influenza, and tuberculosis is associated with undernutrition. Immunosuppression resulting from protein-energy undernutrition severely impacts primary and secondary lymphoid organs involved in the response to related pathogens. The thymus-a primary lymphoid organ responsible for the generation of T lymphocytes-is particularly compromised by both undernutrition and infectious diseases. In this respect, we will discuss herein various intrathymic cellular and molecular interactions seen in undernutrition alone or in combination with acute infections. Many examples illustrated in studies on humans and experimental animals clearly revealed that protein-related undernutrition causes thymic atrophy, with cortical thymocyte depletion. Moreover, the non-lymphoid microenvironmental compartment of the organ undergoes important changes in thymic epithelial cells, including their secretory products such as hormones and extracellular matrix proteins. Of note, deficiencies in vitamins and trace elements also induce thymic atrophy. Interestingly, among the molecular interactions involved in the control of undernutrition-induced thymic atrophy is a hormonal imbalance with a rise in glucocorticoids and a decrease in leptin serum levels. Undernutrition also yields a negative impact of acute infections upon the thymus, frequently with the intrathymic detection of pathogens or their antigens. For instance, undernourished mice infected with Leishmania infantum (that causes VL) undergo drastic thymic atrophy, with significant reduction in thymocyte numbers, and decreased levels of intrathymic chemokines and cytokines, indicating that both lymphoid and microenvironmental compartments of the organ are affected. Lastly, recent data revealed that some probiotic bacteria or probiotic fermented milks improve the thymus status in a model of malnutrition, thus raising a new field for investigation, namely the thymus-gut connection, indicating that probiotics can be envisioned as a further adjuvant therapy in the control of thymic changes in undernutrition accompanied or not by infection.

Humoral immunoresponse elicited against an adenoviral-based SARS-CoV-2 coronavirus vaccine in elderly patients.

The early sequencing of the SARS-CoV-2 viral genome allowed for a speedy development of effective vaccines against the virus. Nevertheless, age-related immunosenescence, the inability to mount strong immune responses, still represents a major obstacle. Here, in a group of 149 elderly volunteers (70-96 years old), evolution of the humoral immune response over time to Gam-COVID-Vac (Sputnik V), a vaccine based on heterologous recombinant adenovirus-26 (Ad26) and adenovirus-5 (Ad5) carrying the Spike genome, was analyzed by an anti-RBD ELISA. At 28 days post vaccination (dpv), a seroconversion rate of 91% was achieved, showing the importance of administering at least two doses of Gam-COVID-Vac to elicit a robust immune response, especially in elderly individuals without previous SARS-CoV-2 infection. Interestingly, IgG specific antibodies that reached their highest titers around 28 dpv (median = 740), persisted without significant decrease after 60 dpv (median = 650). After 90 dpv, IgG titers began to drop, and at 180 dpv only 44.7% of the elderly individuals remained with detectable anti-RBD IgG antibodies. No significant differences were observed in specific humoral immune responses between genders at early times point. However, at 60 dpv anti-RBD titers were more persistent in elderly females, and only dropped at 90 dpv (p < 0.0001). As expected, the highest antibodies titers were elicited in the youngest subgroup (70-74 years). Our results show that Gam-COVID-Vac was able to deal with the ageing of the immune system, eliciting a robust immune response in an elderly cohort, which lasted approximately 90 dpv at high levels, and protected against COVID-19.

Probiotic Consumption Boosts Thymus in Obesity and Senescence Mouse Models.

The ability of the immune system to respond to different pathogens throughout life requires the constant production and selection of T cells in the thymus. This immune organ is very sensitive to age, infectious processes and nutrition disorders (obesity and malnutrition). Several studies have shown that the incorporation of some probiotic bacteria or probiotic fermented milk in the diet has beneficial effects, not only at the intestinal level but also on distant mucosal tissues, improving the architecture of the thymus in a malnutrition model. The aim of the present study was to determine whether supplementation with the probiotic strain Lactobacillus casei CRL 431 and/or its cell wall could improve body weight, intestinal microbiota and thymus structure and function in both obese and aging mice. We evaluated probiotic administration to BALB/c mice in 2 experimental mouse models: obesity and senescence, including mice of different ages (21, 28, 45, 90 and 180 days). Changes in thymus size and histology were recorded. T-lymphocyte population and cytokine production were also determined. The consumption of probiotics improved the cortical/medullary ratio, the production and regulation of cytokines and the recovery of mature T-lymphocyte populations of the thymus in obese and old mice. Probiotic incorporation into the diet could not only modulate the immune system but also lead to thymus function recovery, thus improving quality of life.

Long-term analysis of antibodies elicited by SPUTNIK V: A prospective cohort study in Tucumán, Argentina.

BACKGROUND: Gam-COVID-Vac (SPUTNIK V) has been granted emergency use authorization in 70 nations and has been administered to millions worldwide. However, there are very few peer-reviewed studies describing its effects. Independent reports regarding safety and effectiveness could accelerate the final approval by the WHO. We aimed to study the long-term humoral immune response in naïve and previously infected volunteers who received SPUTNIK V. METHODS: Humoral immune responses, assayed by anti-SARS-CoV-2-spike-RBD IgG ELISA and neutralization assays, were measured in 602 healthcare workers at 0, 14, 28, 60 and 180 days after receiving SPUTNIK V between December 2020 and July 2021 in Tucumán, Argentina. FINDINGS: Seroconversion was detected in 97% of individuals after 28 days post-vaccination (dpv) (N = 405). Anti-RBD titers began to decrease after 60 dpv (N = 328), but remained detectable in 94% at 90 dpv (N = 224). At 180 dpv, anti-RDB titers persisted in 31% (N = 146). Previous infection triggered an increased immune response to the first dose and increased neutralization activity against variants of concern (VOC). Second doses in previously infected individuals further increased titers, even 90 dpv (N = 75). Basal antibody titers had more influence on post-vaccination anti-RBD responses than the time elapsed between diagnosis and vaccination (N = 274). INTERPRETATION: Data presented herein provides essential knowledge regarding the kinetics of antibodies induced by SPUTNIK V up to six months after immunization, and suggests that when considering one-dose vaccination policies for individuals with previous SARS-CoV-2 infection, serological studies to determine basal titers may be important, independent of when diagnosis occurred. FUNDING: Tucumán Public Health System (SIPROSA), Argentinean National Research Council (CONICET), National University of Tucumán (UNT).

Survival effect of probiotics in a rat model of colorectal cancer treated with capecitabine.

BACKGROUND: Probiotics are used to manage a number of gastrointestinal disorders due to their beneficial properties. Clinical reports showed that probiotics also improve the life quality of patients with colorectal cancer (CRC) subjected to oncologic treatment. In a CRC animal model, probiotics supplementation has the potential to decrease the formation of aberrant crypts and ameliorate tumor malignancy, enhancing the antitumor effect of 5-fluorouracil (5-FU) chemotherapy. Based on these data, we hypothesize that the administration of probiotics impact positively in the overall survival and life quality of rats with CRC under the treatment of capecitabine, which is the pro drug of 5-FU. AIM: To evaluate the probiotics effects in a rat CRC model treated with capecitabine and followed until the end of life. METHODS: 1,2-Dimethylhidrazine dihydrochloride (1,2-DMH) was employed as carcinogen inductor of CRC. Fifty male Wistar-Lewis rats were randomly assigned to one of five following groups: Control (n = 5), Control + probiotics (Control-P group, n = 5), 1,2-DMH alone (DMH group, n = 10), 1,2-DMH + capecitabine (DMH-C group, n = 10), 1,2-DMH + probiotics (DMH-P group, n = 10) and 1,2-DMH + capecitabine + probiotics (DMH-C-P group, n = 10). All parametric data were expressed as the mean ± SD. The statistical significance of differences was analyzed using one-way ANOVA. Data were analyzed with InfoStat software. The results were considered statistically significant at P < 0.05. Overall survival was evaluated with the Kaplan-Meier estimator with the log-rank test. RESULTS: The data of mean overall survival for DMH, DMH-P, DMH-C, DMH-C-P, Control and Control-P groups were 250 d [95% confidence interval (CI): 242.5-253.1], 268 d (95%CI: 246.3-271.4), 380 d (95%CI: 337.8-421.9), 480 d (95%CI: 436.9-530.7), 588 d (95%CI: 565.8-609.3) and 590 d (95%CI: 564.3-612.9), respectively, with a significant difference between DMH-C and DMH-C-P groups (P = 0.001). Comparing all groups by Kaplan-Meier estimator, we found a significantly different in the overall survival of DMH and DMH-P groups respect to DMH-C (P = 0.001) and DMH-C-P (P = 0.001) groups; interestingly, there were no meaningful differences between Control, Control-P and DMH-C-P groups (P = 0.012). The tendency of change in body weight gain of the rats at 90 d of finishing DMH administration was similar in Control group compared with DMH-C and DMH-C-P groups; however, and of relevance, DMH-C-P group has experienced a higher body weight gain at the end of animal's life than DMH-C group (P = 0.001). In DMH-C-P group we found a positive effect of probiotics in clinical manifestations since diarrhea, constipation and blood stool were absenting. Also, the tumor burden was lower in DMH-C-P than DMH-C, DMH-P or DMH groups (1.25 vs 1.81 vs 3.9 vs 4.8 cm2, respectively). DMH-C and DMH-C-P groups showed only mucinous carcinoma type while in other DMH groups the tumor types were variable. However, mucinous carcinoma from DMH-C-P group showed invasion until muscularis propria layer. Interestingly, metastatic lymph node was observed in DMH, DMH-C and DMH-P groups but not in DMH-C-P. All animals in Control group died from natural causes without objective injuries. All animals of DMH and DMH-P groups died from tumor complications (i.e., obstruction or intestinal perforation); however, this cause was seen only in 44.5% of DMH-C and DMH-C-P groups. CONCLUSION: Probiotics administration improves life quality of rats with CRC under capecitabine treatment and also has a positive effect in the overall survival of these animals treated with this drug.

Elevated Humoral Immune Response to SARS-CoV-2 at High Altitudes Revealed by an Anti-RBD "In-House" ELISA.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a global pandemic with dramatic health and socioeconomic consequences. The Coronavirus Disease 2019 (COVID-19) challenges health systems to quickly respond by developing new diagnostic strategies that contribute to identify infected individuals, monitor infections, perform contact-tracing, and limit the spread of the virus. In this brief report, we developed a highly sensitive, specific, and precise "In-House" ELISA to correctly discriminate previously SARS-CoV-2-infected and non-infected individuals and study population seroprevalence. Among 758 individuals evaluated for anti-SARS-CoV-2 serology in the province of Tucumán, Argentina, we found a weak correlation between antibodies elicited against the RBD, the receptor-binding domain of the Spike protein, and the nucleocapsid (N) antigens of this virus. Additionally, we detected mild levels of anti-RBD IgG antibodies in 33.6% of individuals diagnosed with COVID-19, while only 19% showed sufficient antibody titers to be considered as plasma donors. No differences in IgG anti-RBD titers were found between women and men, neither in between different age groups ranging from 18 to 60. Surprisingly, individuals from a high altitude village displayed elevated and longer lasting anti-RBD titers compared to those from a lower altitude city. To our knowledge, this is the first report correlating altitude with increased humoral immune response against SARS-CoV-2 infection.

Probiotic Bacteria and Their Cell Walls Induce Th1-Type Immunity Against Salmonella Typhimurium Challenge.

Probiotics have been associated with a variety of health benefits. They can act as adjuvant to enhance specific immune response. Bacterial cell wall (CW) molecules are key structures that interact with host receptors promoting probiotic effects. The adjuvant capacity underlying this sub-cellular fraction purified from Lactobacillus casei CRL431 and L. paracasei CNCMI-1518 remains to be characterized. We interrogated the molecular and cellular events after oral feeding with probiotic-derived CW in addition to heat-inactivated Salmonella Typhimurium and their subsequent protective capacity against S. Typhimurium challenge. Intact probiotic bacteria were orally administered for comparison. We find that previous oral feeding with probiotics or their sub-cellular fraction reduce bacterial burden in spleen and liver after Salmonella challenge. Antibody responses after pathogen challenge were negligible, characterized by not major changes in the antibody-mediated phagocytic activity, and in the levels of total and Salmonella-specific intestinal sIgA and serum IgG, respectively. Conversely, the beneficial effect of probiotic-derived CW after S. Typhimurium challenge were ascribed to a Th1-type cell-mediated immunity which was characterized by augmentation of the delayed-type hypersensitivity response. The cell-mediated immunity associated with the oral feeding with probiotic-derived CW was accompanied with a Th1-cell polarizing cytokines, distinguished by increase IFN-γ/IL-4 ratio. Similar results were observed with the intact probiotics. Our study identified molecular events associated with the oral administration of sub-cellular structures derived from probiotics and their adjuvant capacity to exert immune modulatory function.

Probiotic lactobacilli as a promising strategy to ameliorate disorders associated with intestinal inflammation induced by a non-steroidal anti-inflammatory drug.

Damage to the small intestine caused by non-steroidal anti-inflammatory drugs (NSAIDs) occurs more frequently than in the upper gastrointestinal tract, is more difficult to diagnose and no effective treatments exist. Hence, we investigated whether probiotics can control the onset of this severe condition in a murine model of intestinal inflammation induced by the NSAID, indomethacin. Probiotic supplementation to mice reduce the body weight loss, anemia, shortening of the small intestine, cell infiltration into the intestinal tissue and the loss of Paneth and Goblet cells associated with intestinal inflammation. Furthermore, a high antimicrobial activity in the intestinal fluids of mice fed with probiotics compared to animals on a conventional diet was elicited against several pathogens. Interestingly, probiotics dampened the oxidative stress and several local and systemic markers of an inflammatory process, as well as increased the secretion of IL-10 by regulatory T cells. Even more importantly, probiotics induced important changes in the large intestine microbiota characterized by an increase in anaerobes and lactobacilli, and a significant decrease in total enterobacteria. We conclude that oral probiotic supplementation in NSAID-induced inflammation increases intestinal antimicrobial activity and reinforces the intestinal epithelial barrier in order to avoid pathogens and commensal invasion and maintain intestinal homeostasis.

Beneficial Effects of Probiotic Consumption on the Immune System.

BACKGROUND: The gastrointestinal tract is one of the most microbiologically active ecosystems that plays a crucial role in the working of the mucosal immune system (MIS). In this ecosystem, the consumed probiotics stimulate the immune system and induce a network of signals mediated by the whole bacteria or their cell wall structure. This review is aimed at describing the immunological mechanisms of probiotics and their beneficial effects on the host. SUMMARY: Once administered, oral probiotic bacteria interact with the intestinal epithelial cells (IECs) or immune cells associated with the lamina propria, through Toll-like receptors, and induce the production of different cytokines or chemokines. Macrophage chemoattractant protein 1, produced by the IECs, sends signals to other immune cells leading to the activation of the MIS, characterized by an increase in immunoglobulin A+ cells of the intestine, bronchus and mammary glands, and the activation of T cells. Specifically, probiotics activate regulatory T cells that release IL-10. Interestingly, probiotics reinforce the intestinal barrier by an increase of the mucins, the tight junction proteins and the Goblet and Paneth cells. Another proposed mechanism of probiotics is the modulation of intestinal microbiota by maintaining the balance and suppressing the growth of potential pathogenic bacteria in the gut. Furthermore, it has been demonstrated that long-term probiotics consumption does not affect the intestinal homeostasis. The viability of probiotics is crucial in the interaction with IECs and macrophages favoring, mainly, the innate immune response. Macrophages and Dendritic cells (DCs) play an important role in this immune response without inducing an inflammatory pattern, just a slight increase in the cellularity of the lamina propria. Besides, as part of the machinery that probiotics activate to protect against different pathogens, an increase in the microbicidal activity of peritoneal and spleen macrophages has been reported. In malnutrition models, such as undernourishment and obesity, probiotic was able to increase the intestinal and systemic immune response. Furthermore, probiotics contribute to recover the histology of both the intestine and the thymus damaged in these conditions. Probiotic bacteria are emerging as a safe and natural strategy for allergy prevention and treatment. Different mechanisms such as the generation of cytokines from activated pro-T-helper type 1, which favor the production of IgG instead of IgE, have been proposed. Key Messages: Probiotic bacteria, their cell walls or probiotic fermented milk have significant effects on the functionality of the mucosal and systemic immune systems through the activation of multiple immune mechanisms.

Oral Administration of Probiotics Increases Paneth Cells and Intestinal Antimicrobial Activity.

The huge amount of intestinal bacteria represents a continuing threat to the intestinal barrier. To meet this challenge, gut epithelial cells produce antimicrobial peptides (AMP) that act at the forefront of innate immunity. We explore whether this antimicrobial activity and Paneth cells, the main intestinal cell responsible of AMP production, are influenced by probiotics administration, to avoid the imbalance of intestinal microbiota and preserve intestinal barrier. Administration of Lactobacillus casei CRL 431 (Lc 431) and L. paracasei CNCM I-1518 (Lp 1518) to 42 days old mice, increases the number of Paneth cells on small intestine, and the antimicrobial activity against the pathogens Staphylococcus aureus and Salmonella Typhimurium in the intestinal fluids. Specifically, strong damage of the bacterial cell with leakage of cytoplasmic content, and cellular fragmentation were observed in S. Typhimurium and S. aureus. Even more important, probiotics increase the antimicrobial activity of the intestinal fluids at the different ages, from weaning (21 days old) to old age (180 days old). Intestinal antimicrobial activity stimulated by oral probiotics, do not influence significantly the composition of total anaerobic bacteria, lactobacilli and enterobacteria in the large intestine, at any age analyzed. This result, together with the antimicrobial activity observed against the same probiotic bacteria; endorse the regular consumption of probiotics without adverse effect on the intestinal homeostasis in healthy individuals. We demonstrate that oral probiotics increase intestinal antimicrobial activity and Paneth cells in order to strengthen epithelial barrier against pathogens. This effect would be another important mechanism by which probiotics protect the host mainly against infectious diseases.

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

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

Probiotic fermented milk consumption modulates the allergic process induced by ovoalbumin in mice.

Orally administered probiotic micro-organisms are able to regulate the exacerbated immune response during the antigenic sensitisation process. The aim of the present study was to evaluate the potential efficacy of probiotic fermented milk (PFM) in preventing or treating allergy in an experimental model, and to investigate its underlying mechanisms. Ovoalbumin (OVA)-sensitised BALB/c mice were fed with PFM before the sensitisation procedure or fed continuously with PFM. At 7 and 15 d post-sensitisation, anti-OVA-specific IgE, IgG, IgG1 and IgG2a concentrations were measured in the serum and broncho-alveolar lavage fluid (BALF). Concentrations of interferon-γ (IFN-γ), IL-4, IL-10 and total secretory IgA (S-IgA) were measured in the supernatants of macerated lungs or in the BALF. The levels of IgA+, CD4+ and CD8+ T lymphocytes and F4/80+ cells were measured in the lungs by immunofluorescence. Inducible CD4+/CD25/Foxp3+ regulatory T (Treg) cells were evaluated in the lungs. PFM shifted the T helper (Th)2 profile response towards a Th1 response that led to the production of IgG instead of IgE, with increasing levels of IL-10 and IFN-γ that play an important role in immunomodulation exerted by PFM administration in sensitised mice. Anti-OVA-specific IgE levels were significantly decreased; however, there was no modification in the levels of anti-OVA-specific IgG and total S-IgA. PFM did not influence Treg cells in treated mice. Consumption of PFM could be a promising strategy in the amelioration of airway allergies, considering that the effect is mediated by the production of IgG through the activation of Th1 instead of the direct activation of Th2 cells to produce IgE.

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

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

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

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

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

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

Evaluation of immune response, microbiota, and blood markers after probiotic bacteria administration in obese mice induced by a high-fat diet.

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 60 d. 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.

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

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

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

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

Influence of a probiotic lactobacillus strain on the intestinal ecosystem in a stress model mouse.

Daily exposure to stressful situations affects the health of humans and animals. It has been shown that psychological stress affects the immune system and can exacerbate diseases. Probiotics can act as biological immunomodulators in healthy people, increasing both intestinal and systemic immune responses. The use of probiotics in stress situations may aid in reinforcing the immune system. The aim of this study was to evaluate the effect of a probiotic bacterium on the gut immune system of mice that were exposed to an experimental model of stress induced by food and mobility restriction. The current study focused on immune cells associated with the lamina propria of the intestine, including CD4+ and CD8+ T lymphocytes, CD11b+ macrophages, CD11c+ dendritic cells, and IgA+ B lymphocytes, as well as the concentrations of secretory IgA (S-IgA) and cytokine interferon gamma (INF-γ in intestinal fluid. We also evaluated the probiotic's influence on the gut microbiota. Probiotic administration increased IgA producing cells, CD4+ cells in the lamina propria of the small intestine, and S-IgA in the lumen; it also reduced the levels of IFN-γ that had increased during stress and improved the intestinal microbiota as measured by an increase in the lactobacilli population. The results obtained from administration of the probiotic to stressed mice suggest that the use of food containing these microorganisms may work as a palliative to reinforce the immune system.