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We hypothesized that in individuals with previous SARS-CoV-2 infection, the first vaccine dose would work as a booster, eliciting a faster and more intense immune response. We herein describe antibody responses to the first and second doses of Gam-COVID-Vac (SPUTNIK V) vaccine in health personnel of Tucuman, Argentina, with previous COVID-19 and compared it with uninfected personnel. Individuals with anti-SARS-CoV-2 titers at baseline showed significantly higher responses to the first dose than people with no prior history of disease (p <0.0001), with titers higher to those registered after the second dose in the control group, representing a clear secondary antibody response. This suggests that a single dose of SPUTNIK V for people with previous SARS-CoV-2 infection could contribute to a better use of available doses. One-Sentence SummaryFirst vaccine dose in subjects with prior COVID19 elicits a higher antibody response than two doses in uninfected individuals
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The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) first reported in Wuhan has caused a global pandemic with dramatic health and socioeconomic consequences. The Coronavirus Disease 2019 (COVID-19) associated represents a challenge for health systems that had to quickly respond developing new diagnostic and therapeutic strategies. In the present work, we developed an "In House" ELISA with high sensitivity (92.2 %), specificity (100%) and precision (93.9%), with an area under the ROC curve (AUC) of 0.991, rendering the assay as an excellent serological test to correctly discriminate between SARS-COv-2 infected and non-infected individuals and study population seroprevalence. Among 758 patients evaluated for SARS-CoV-2 diagnosis in the province of Tucuman, Argentina, we found a Pearson correlation coefficient of 0.5048 between antibodies elicited against the RBD and the nucleocapsid (N) antigen. Additionally, 33.6% of individuals diagnosed with COVID-19 displayed mild levels of RBD-IgG antibodies, while 19% of the patients showed high antibody titers. Interestingly, patients with SARS-COV-2 infection over 60 years old elicited significantly higher levels of IgG antibodies against RBD compared to younger ones, while no difference was found between women and men. Surprisingly, individuals from a high altitude village displayed statistically significant higher and longer lasting anti-RBD antibodies compared to those from a city at a lower altitude, suggesting that a hypobaric hypoxia-adapted mechanism may act as a protective factor for COVID-19. To our knowledge, this is the first report correlating altitude with increased humoral immune response against SARS-Cov-2 infection.
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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.
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Antiinflamatorios no Esteroideos/efectos adversos , Suplementos Dietéticos , Microbioma Gastrointestinal , Enfermedades Inflamatorias del Intestino/inducido químicamente , Enfermedades Inflamatorias del Intestino/microbiología , Lactobacillus , Probióticos/administración & dosificación , Administración Oral , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Modelos Animales de Enfermedad , Células Caliciformes/patología , Indometacina/administración & dosificación , Indometacina/efectos adversos , Inflamación , Enfermedades Inflamatorias del Intestino/patología , Enfermedades Inflamatorias del Intestino/prevención & control , Interleucina-10/metabolismo , Intestinos/citología , Intestinos/patología , Ratones Endogámicos BALB C , Estrés Oxidativo , Linfocitos T Reguladores/metabolismoRESUMEN
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.
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Dieta Alta en Grasa/efectos adversos , Intestino Delgado , Lacticaseibacillus casei , Microbiota , Obesidad/tratamiento farmacológico , Probióticos/uso terapéutico , Pérdida de Peso , Animales , Bacteroides/crecimiento & desarrollo , Bifidobacterium/crecimiento & desarrollo , Biomarcadores/sangre , Grasas de la Dieta/efectos adversos , Femenino , Inmunidad Mucosa , Inmunoglobulina A/metabolismo , Mucosa Intestinal/inmunología , Mucosa Intestinal/microbiología , Intestino Delgado/inmunología , Intestino Delgado/microbiología , Intestino Delgado/patología , Hígado/patología , Macrófagos/metabolismo , Ratones Endogámicos BALB C , Ratones Obesos , Obesidad/sangre , Obesidad/complicaciones , Obesidad/microbiología , FagocitosisRESUMEN
Food fortification may be carried out to improve the health status of consumers. In this study, peanut skins were added at 1.3, 1.8, and 2.5% to cookies to increase their polyphenol content. Insoluble fiber was increased by up to 52%. In addition, total phenolic content and the corresponding antioxidant capacities also increased as evidenced by increases of epicatechin and procyanidin dimers A and B. In addition, trimers and tetramers of procyanidins were identified only in peanut skin-fortified cookies. Addition of 2.5% peanut skins rendered an increase of up to 30% in the total polyphenols as evaluated by high-performance liquid chromatography-diode array detection-electrospray ionization multistage mass spectrometry (HPLC-DAD-ESI-MS(n)). Sensory evaluation results demonstrated that peanut skin-fortified cookies were well accepted, which suggests that the present formulation may lend itself for commercial exploitation.
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Antioxidantes/química , Arachis/química , Aditivos Alimentarios/química , Alimentos Fortificados/análisis , Polifenoles/química , Gusto , Adolescente , Adulto , Cromatografía Líquida de Alta Presión , Fibras de la Dieta/análisis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Espectrometría de Masa por Ionización de Electrospray , Adulto JovenRESUMEN
Proteinenergy malnutrition (PEM) causes a significant impairment of the immune system, the thymus being one of the most affected organs. It has been demonstrated that the administration of probiotic fermented milk (PFM) recovered the intestinal barrier, histological alterations and mucosal and systemic immune functions in a non-severe malnutrition model using BALB/c mice. The aim of the present study was to evaluate, in the same model of malnutrition, the effect of a PFM added to a re-nutrition diet on the recovery of the thymus, analysing histological and functional alterations caused by malnutrition. Mice were undernourished and divided into three groups according to the dietary supplement received during re-nutrition: milk, PFM or its bacterial-free supernatant (BFS). They were compared with well-nourished and malnourished mice. PFM was the most effective re-nutrition supplement to improve the histology of the thymus, decreasing cellular apoptosis in this organ and recovering the percentage of CD4þ/CD82 single-positive thymocytes. Immature doublepositive thymocytes were increased in the malnourished control (MC). The production of different cytokines in the thymus was increased in mice given PFM, compared with the mice that received other dietary supplements and MC. Mice given the BFS presented an improvement in the thymus similar to those that received milk. We demonstrated the importance of the whole PFM supplementation on the histological and functional recovery of the thymus in a non-severe PEM model.
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Citocinas/metabolismo , Suplementos Dietéticos , Leche/microbiología , Probióticos/uso terapéutico , Desnutrición Proteico-Calórica/dietoterapia , Timocitos/efectos de los fármacos , Timo/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Antígenos CD4/metabolismo , Femenino , Fermentación , Microbiología de Alimentos , Proteína Kangai-1/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Desnutrición Proteico-Calórica/inmunología , Desnutrición Proteico-Calórica/metabolismo , Índice de Severidad de la Enfermedad , Timocitos/metabolismo , Timo/citología , Timo/inmunología , Timo/metabolismoRESUMEN
The intestinal ecosystem contains a normal microbiota, non-immune cells and immune cells associated with the intestinal mucosa. The mechanisms involved in the modulation of the gut immune system by probiotics are not yet completely understood. The present work studies the effect of a fermented milk containing probiotic bacterium Lactobacillus (Lb.) casei DN114001 on different parameters of the gut immune system involved with the nonspecific, innate and adaptive response. BALB/c mice received the probiotic bacterium Lb. casei DN114001 or the probiotic fermented milk (PFM). The interaction of the probiotic bacteria with the intestine was studied by electron and fluorescence microscopy. The immunological parameters were studied in the intestinal tissue and in the supernatant of intestinal cells (IC). Results showed that the probiotic bacterium interact with the IC. The whole bacterium or its fragments make contact with the gut associated immune cells. The PFM stimulated the IC with IL-6 release, as well as cells related to the nonspecific barrier and with the immune cells associated with the gut. This last activity was observed through the increase in the population of different immune cells: T lymphocytes and IgA+ B lymphocytes, and by the expression of cell markers related to both innate and adaptive response (macrophages). PFM was also able to activate the enzyme calcineurine responsible for the activation of the transcriptional factor NFAT. PFM induced mucosal immune stimulation reinforcing the non-specific barrier and modulating the innate immune response in the gut, maintaining the intestinal homeostasis.
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Adyuvantes Inmunológicos/farmacología , Productos Lácteos Cultivados , Lacticaseibacillus casei/fisiología , Probióticos/farmacología , Animales , Regulación de la Expresión Génica/inmunología , Células Caliciformes/citología , Inmunoglobulina A/metabolismo , Inmunoglobulinas/metabolismo , Interleucina-6/metabolismo , Mucosa Intestinal/citología , Intestinos/microbiología , Linfocitos/metabolismo , Ratones , Ratones Endogámicos BALB C , Factores de Transcripción NFATC/genética , Factores de Transcripción NFATC/metabolismoRESUMEN
BACKGROUND: Microbial colonization of the intestine after birth is an important step for the development of the gut immune system. The acquisition of passive immunity through breast-feeding may influence the pattern of bacterial colonization in the newborn. The aim of this work was to evaluate the effect of the administration of a probiotic fermented milk (PFM) containing yogurt starter cultures and the probiotic bacteria strain Lactobacillus casei DN-114001 to mothers during nursing or their offspring, on the intestinal bacterial population and on parameters of the gut immune system. RESULTS: Fifteen mice of each group were sacrificed at ages 12, 21, 28 and 45 days. Large intestines were taken for determination of intestinal microbiota, and small intestines for the study of secretory-IgA (S-IgA) in fluid and the study of IgA+ cells, macrophages, dendritic cells and goblet cells on tissue samples. The consumption of the PFM either by the mother during nursing or by the offspring after weaning modified the development of bifidobacteria population in the large intestine of the mice. These modifications were accompanied with a decrease of enterobacteria population. The administration of this PFM to the mothers improved their own immune system and this also affected their offspring. Offspring from mice that received PFM increased S-IgA in intestinal fluids, which mainly originated from their mother's immune system. A decrease in the number of macrophages, dendritic cells and IgA+ cells during the suckling period in offspring fed with PFM was observed; this could be related with the improvement of the immunity of the mothers, which passively protect their babies. At day 45, the mice reach maturity of their own immune system and the effects of the PFM was the stimulation of their mucosal immunity. CONCLUSION: The present work shows the beneficial effect of the administration of a PFM not only to the mothers during the suckling period but also to their offspring after weaning and until adulthood. This effect positively improved the intestinal microbiota that are related with a modulation of the gut immune response, which was demonstrated with the stimulation of the IgA + cells, macrophages and dendritic cells.