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To stimulate discussion around the topic of 'carbohydrates' and health, the Brazilian branch of the International Life Sciences Institute held the 11th International Functional Foods Workshop (12 December 2011) in which consolidated knowledge and recent scientific advances specific to the relationship between carbohydrates and health were presented. As part of this meeting, several key points related to dietary fiber, glycemic response, fructose, and impacts on satiety, cognition, mood, and gut microbiota were realized: 1) there is a need for global harmonization of a science-based fiber definition; 2) low-glycemic index foods can be used to modulate the postprandial glycemic response and may affect diabetes and cardiovascular outcomes; 3) carbohydrate type may influence satiety and satiation; glycemic load and glycemic index show links to memory, mood, and concentration; 4) validated biomarkers are needed to demonstrate the known prebiotic effect of carbohydrates; 5) negative effects of fructose are not evident when human data are systematically reviewed; 6) new research indicates that diet strongly influences the microbiome; and 7) there is mounting evidence that the intestinal microbiota has the ability to impact the gut-brain axis. Overall, there is much promise for development of functional foods that impact the microbiome and other factors relevant to health, including glycemic response (glycemic index/glycemic load), satiety, mood, cognition, and weight management. [ABSTRACT FROM AUTHOR]

Interleukin-10 (IL-10) is the most important anti-inflammatory cytokine at intestinal level, and its absence is involved in inflammatory bowel diseases. However, oral treatment with IL-10 is difficult because of its low survival in the gastrointestinal tract and systemic treatments lead to undesirable side effects. The aim of this paper was to evaluate the anti-inflammatory effect of the administration of milks fermented by Lactococcus lactis strains that produce IL-10 under the control of the xylose-inducible expression system using a trinitrobenzenesulfonic acid-induced colitis murine model. Mice that received milks fermented by L. lactis strains producing IL-10 in the cytoplasm (Cyt strain) or secreted to the product (Sec strain) showed lower damage scores in their large intestines, decreased IFN-γ levels in their intestinal fluids and lower microbial translocation to liver, compared to mice receiving milk fermented by the wild-type strain or those not receiving any treatment. The results obtained in this study show that the employment of fermented milks as a new form of administration of IL-10-producing L. lactisis effective in the prevention of inflammatory bowel disease in a murine model. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Crohn's disease and ulcerative colitis, two forms of inflammatory bowel disease, are important problems in industrialized countries. The complete etiology of these two diseases is still unknown but likely involves genetic, environmental, and immunological factors. The aim of the present work was to determine whether the anti-inflammatory effects reported for yoghurt in acute trinitrobenzene sulfonic acid-induced intestinal inflammation in mice also could prevent or attenuate the recurrent intestinal inflammation, thus maintaining remission. The innate response also was evaluated through participation of Toll-like receptors (TLRs) and the analysis of T-cell populations to determine the effects of yoghurt in an acute inflammatory bowel disease model. Yoghurt exerted a beneficial effect on acute intestinal inflammation by regulating T-cell expansion and modulating the expression of TLRs, with decrease of TLR4+ and increase of TLR9+ cells. The anti-inflammatory effect of yoghurt also was demonstrated in a recurrent inflammation model. Yoghurt administration during the remission phase prevented the recurrence of inflammation without producing undesirable side effects. The yoghurt effect may be mediated by increased interleukin 10 production and changes in intestinal microbiota. [ABSTRACT FROM AUTHOR]

Previous studies on a murine model have demonstrated that the administration of Lactobacillus helveticus and Lactobacillus casei inhibits the development of fibrosarcoma and colon carcinoma, respectively. The aim of this work was to study the beneficial effects of the consumption of milk fermented by L. helveticus on a murine model for mammary carcinoma. Female BALB/c mice were challenged by a single subcutaneous injection of tumoral cells (American Type Culture Collection 4T1) in the left mammary gland. Prior to tumour injection, mice were fed for two, five or seven consecutive days with fermented milk. The following factors were monitored for 2 months: rate of tumour development, histological studies, apoptosis, phagocytic index, peritoneal macrophages, determination of β-glucuronidase enzyme in peritoneal macrophages, determination of γ-interferon (INFγ) and tumour necrosis factor-α (TNF-α) in blood serum, determination of CD4+, CD8+, interleukin-6 (IL-6), IL-10, TNF-α and INFγ by immunoperoxidase, and measurement of β-glucuronidase activity in intestinal fluid. The administration of L. helveticus delayed the development of the tumour in all cases, a 2- or 7-day feeding period being most effective. This work demonstrates that milk fermented with L. helveticus decreases the growth rate of mammary tumours. The effect was mediated by increased apoptosis and decreased production of pro-inflammatory cytokines, in particular IL-6, implicated in oestrogen synthesis. [ABSTRACT FROM AUTHOR]

The immunomodulating effect of lactic acid bacteria (LAB) on the gut associated lymphoid tissue (GALT) and the protective capacity of some of them against enteric infections is well documented. The ability of enteroinvasive pathogens to disseminate into the deep tissues by cellular apoptosis induction is also demonstrated. Peritoneal macrophages from BALB/c mice were used to performed in vitro apoptosis assays and to determine oxidant radicals production induced by Lactobacillus delbrueckii ssp. bulgaricus and Streptococcus thermophilus, against an in vitro Salmonella typhimurium infection. We determined whether or not the LAB assayed induces apoptosis inhibition of macrophages infected with the pathogen. Fluorescent DNA fragmentation assay (Tunel test) was used to investigate the ability of the LAB to inhibit macrophage's apoptosis. We determined that Lactobacillus and Streptococcus were able to inhibit the apoptosis of macrophages induced by Sal. typhimurium, L. delbrueckii ssp. bulgaricus being the more effective one. The results suggest that these microorganisms could play a role in apoptotic mechanisms, since the inhibition of it would avoid pathogen disemination. The knowledge that S. thermophilus and L. delbrueckii ssp. bulgaricus have immunopotentiation capacity led us to demonstrate that such apoptosis inhibition observed might be mediated by other process such as the release of oxidant radicals able to kill the pathogen. The preventive effect of LAB against Sal. typhimurium infection could be mediated by apoptosis inhibition. [ABSTRACT FROM AUTHOR]

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In previous papers we demonstrated the influence of the oral administration of different lactic acid bacteria on the systemic immune response and the protective effect against an infection with Candida albicans in a corticoid immunosuppressed experimental model in mice. The gastrointestinal and respiratory tracts are the most common sites of entry of the infectious agents at the mucosal surfaces. The IgA secreting cells and mastocytes play an important role in host defence against pathogens. The aim of this study was to determine whether or not some lactobacilli strains have influence on the number of IgA and mast cells associated with the gut and bronchus mucosa, in mice immunosuppressed by corticoid therapy. Groups of animals were immunosuppressed by corticoid oral administration (50 mg kg-1). They were split into four experimental groups: immunosuppressed control mice and the immunosuppressed test groups, which were given L. casei, L. delbruecki subsp. bulgaricus or L. acidophilus at a concentration of 1 X 109 cells/day/mouse, on days 8 and 9 post-corticoid. We demonstrated that the lactobacilli strains assayed were able to increase the number of IgA secreting cells and mast cells associated with both gut and bronchus mucosa, the effect being more remarkable for L. delbruecki subsp. bulgaricus. The enhancement of the IgA secreting cells and mast cells, in an immunosuppressed host induced by lactobacilli administration specially by L. delbruecki subsp. bulgaricus, suggest the potential of its use as adjuvant therapy to protect mucosal surfaces. [ABSTRACT FROM AUTHOR]

Abstract: 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 7days 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. [Copyright &y& Elsevier]

Abstract: 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 LAB were 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 LAB showed 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 LAB that produce antioxidant enzymes could be used to prevent or decrease the severity of certain intestinal pathologies. [Copyright &y& Elsevier]

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Savino, Durães, Maldonado-Galdeano, Perdigon, Mendes-da-Cruz and Cuervo.)

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 cm 2 , 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., Competing Interests: Conflict-of-interest statement: The authors declare that they have no competing interests., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Interleukin-10 (IL-10) is the most important anti-inflammatory cytokine at intestinal level, and its absence is involved in inflammatory bowel diseases. However, oral treatment with IL-10 is difficult because of its low survival in the gastrointestinal tract and systemic treatments lead to undesirable side effects. The aim of this paper was to evaluate the anti-inflammatory effect of the administration of milks fermented by Lactococcus lactis strains that produce IL-10 under the control of the xylose-inducible expression system using a trinitrobenzenesulfonic acid-induced colitis murine model. Mice that received milks fermented by L. lactis strains producing IL-10 in the cytoplasm (Cyt strain) or secreted to the product (Sec strain) showed lower damage scores in their large intestines, decreased IFN-γ levels in their intestinal fluids and lower microbial translocation to liver, compared to mice receiving milk fermented by the wild-type strain or those not receiving any treatment. The results obtained in this study show that the employment of fermented milks as a new form of administration of IL-10-producing L. lactisis effective in the prevention of inflammatory bowel disease in a murine model., (Copyright © 2012 S. Karger AG, Basel.)

The mechanisms by which probiotic bacteria exert their effects on the immune system are not completely understood, but the epithelium may be a crucial player in the orchestration of the effects induced. In a previous work, we observed that some orally administered strains of lactic acid bacteria (LAB) increased the number of immunoglobulin A (IgA)-producing cells in the small intestine without a concomitant increase in the CD4(+) T-cell population, indicating that some LAB strains induce clonal expansion only of B cells triggered to produce IgA. The present work aimed to study the cytokines induced by the interaction of probiotic LAB with murine intestinal epithelial cells (IEC) in healthy animals. We focused our investigation mainly on the secretion of interleukin 6 (IL-6) necessary for the clonal expansion of B cells previously observed with probiotic bacteria. The role of Toll-like receptors (TLRs) in such interaction was also addressed. The cytokines released by primary cultures of IEC in animals fed with Lactobacillus casei CRL 431 or Lactobacillus helveticus R389 were determined. Cytokines were also determined in the supernatants of primary cultures of IEC of unfed animals challenged with different concentrations of viable or nonviable lactobacilli and Escherichia coli, previously blocked or not with anti-TLR2 and anti-TLR4. We concluded that the small intestine is the place where a major distinction would occur between probiotic LAB and pathogens. This distinction comprises the type of cytokines released and the magnitude of the response, cutting across the line that separates IL-6 necessary for B-cell differentiation, which was the case with probiotic lactobacilli, from inflammatory levels of IL-6 for pathogens.

Nutritional deficiencies are associated with impaired immune response, affecting the body's defence mechanisms. It is also known that Lactic Acid Bacteria (LAB) and fermented products such us yogurt have immunopotentiator activity and nutritional properties, and could thus be used as a valuable supplement in a renutrition diet. The aim of this study was to determine, in a non-severe malnutrition model, the effective dose of Lactobacillus casei (L. casei), which when is used as an adjuvant in a renutrition diet, would modulate the mucosal immune system and induce recovery of the integrity of the intestinal barrier. The experiments were performed on groups of malnourished and renourished BALB/c mice. They received after milk renutrition a supplement of different doses and periods of L. casei feeding. We measured body weight; hematologic values and serum proteins. We also characterized small intestine immunoglobulin secreting cells, intraepithelial leukocytes, mastocytes and goblet cells. Structural and ultrastructural studies were performed. Our results suggest that impaired gut barrier and mucosal immune function produced by malnutrition can be reversed by L. casei and that the dose of 10(7) cfu/day/mouse administered during 5 consecutive days was the optimal one for recovery of the gut mucosal immune system. The clinical significance of these findings suggests ways for improving mucosal immunity, and generating protection against enteropathogens in hosts immunosuppressed by malnutrition.

The present studies were designed to investigate the effect of orally administered Lactobacillus casei , Lactobacillus acidophilus , Lactobacillus delbrueckii spp., bulgaricus , and Streptococcus salivarius ssp. thermophilus on local mucosal immunity in response to enteropathogens. Normal mice were protected against Salmonella typhimurium infection by previous feeding with L. casei and S. salivarius spp. thermophilus , while L. acidophilus and L. delbrueckii spp. bulgaricus were not effective. The protective effect of L. casei against S. typhimurium was associated mainly to IgA production in intestinal secretions. We observed significant differences in the intestinal fluid anti- Salmonella agglutinin titers between the Salmonella -challenged control group (without lactobacilli feeding) and mice pretreated with L. casei . The level of immunoglobulins from intestinal fluid of mice fed previously with lactic acid bacteria was measured by radial immunodiffusion assay showing in all cases an increase in the immunoglobulin concentrations. By Immunoelectrophoresis methods, we observed the presence of two lines of immunoprecipitation. When we used monospecific serum, we detected the presence of IgG and IgA. Elisa tests showed high levels of IgA to S. typhimurium in intestinal secretions of mice pretreated with L. casei , while L. acidophilus and L. delbrueckii spp. bulgaricus groups showed values at slightly higher levels than the controls. The levels of IgG to S. typhimurium were similar to controls in all cases. We did not observe antibodies against the pathogen in intestinal fluid from mice fed with S. salivarius spp. thermophilus . However, we detected anti- Streptococcus antibodies. These results show that only L. casei increases the IgA production secreted to the intestinal lumen, providing adequate defenses at mucosal surfaces, and suggest that this microorganism could be used as oral adjuvant especially to prevent enteric infections.

The effects of an orally-administered mixture of Lactobacillus casei and Lactobacillus acidophilus on the immune system in Swiss albino mice were studied. Non-fermented milk containing viable cultures of both microorganisms was fed for different consecutive days to the animals, the effect of such feeding on their immune system was evinced by macrophage and lymphocyte activation. An increase both in the in vitro phagocytic activity of peritoneal macrophages and in the carbon clearance activity was observed. As regard the lymphocytic activity, the mixture produced a higher activation than that in the control mice. The enhanced macrophage and lymphocytic activity by administering cultures via the oral route, suggest the advisability of using the mixture of bacteria for a more efficient stimulation of the host immune response.