Early-Life Supplementation Enhances Gastrointestinal Immunity and Microbiota in Young Rats.

Immunonutrition, which focuses on specific nutrients in breast milk and post-weaning diets, plays a crucial role in supporting infants' immune system development. This study explored the impact of maternal supplementation with Bifidobacterium breve M-16V and a combination of short-chain galacto-oligosaccharide (scGOS) and long-chain fructo-oligosaccharide (lcFOS) from pregnancy through lactation, extending into the early childhood of the offspring. The synbiotic supplementation's effects were examined at both mucosal and systemic levels. While the supplementation did not influence their overall growth, water intake, or food consumption, a trophic effect was observed in the small intestine, enhancing its weight, length, width, and microscopic structures. A gene expression analysis indicated a reduction in FcRn and Blimp1 and an increase in Zo1 and Tlr9, suggesting enhanced maturation and barrier function. Intestinal immunoglobulin (Ig) A levels remained unaffected, while cecal IgA levels decreased. The synbiotic supplementation led to an increased abundance of total bacteria and Ig-coated bacteria in the cecum. The abundance of Bifidobacterium increased in both the intestine and cecum. Short-chain fatty acid production decreased in the intestine but increased in the cecum due to the synbiotic supplementation. Systemically, the Ig profiles remained unaffected. In conclusion, maternal synbiotic supplementation during gestation, lactation, and early life is established as a new strategy to improve the maturation and functionality of the gastrointestinal barrier. Additionally, it participates in the microbiota colonization of the gut, leading to a healthier composition.

Impact of maternal Bifidobacterium breve M-16V and scGOS/lcFOS supplementation during pregnancy and lactation on the maternal immune system and milk composition.

Introduction: Maternal synbiotic supplementation during pregnancy and lactation can significantly influence the immune system. Prebiotics and probiotics have a positive impact on the immune system by preventing or ameliorating among others intestinal disorders. This study focused on the immunomodulatory effects of B. breve M-16V and short chain galacto-oligosaccharides (scGOS)/long chain fructo-oligosachairdes (lcFOS), including systemic and mucosal compartments and milk composition. Methods: Lewis rats were orally administered with the synbiotic or vehicle during pregnancy (21 days) and lactation (21 days). At the weaning day, small intestine (SI), mammary gland (MG), adipose tissue, milk, mesenteric lymph nodes (MLN), salivary gland (SG), feces and cecal content were collected from the mothers. Results: The immunoglobulinome profile showed increased IgG2c in plasma and milk, as well as elevated sIgA in feces at weaning. The supplementation improved lipid metabolism through enhanced brown adipose tissue activity and reinforced the intestinal barrier by increasing the expression of Muc3, Cldn4, and Ocln. The higher production of short chain fatty acids in the cecum and increased Bifidobacterium counts suggest a potential positive impact on the gastrointestinal tract. Discussion: These findings indicate that maternal synbiotic supplementation during gestation and lactation improves their immunological status and improved milk composition.

Maternal Synbiotic Supplementation with B. breve M-16V and scGOS/lcFOS Shape Offspring Immune Development and Gut Microbiota at the End of Suckling.

Immune system development during gestation and suckling is significantly modulated by maternal environmental and dietary factors. Breastfeeding is widely recognized as the optimal source of nutrition for infant growth and immune maturation, and its composition can be modulated by the maternal diet. In the present work, we investigated whether oral supplementation with Bifidobacterium breve M-16V and short-chain galacto-oligosaccharide (scGOS) and long-chain fructo-oligosaccharide (lcFOS) to rat dams during gestation and lactation has an impact on the immune system and microbiota composition of the offspring at day 21 of life. On that day, blood, adipose tissue, small intestine (SI), mesenteric lymph nodes (MLN), salivary gland (SG), cecum, and spleen were collected. Synbiotic supplementation did not affect the overall body or organ growth of the pups. The gene expression of Tlr9, Muc2, IgA, and Blimp1 were upregulated in the SI, and the increase in IgA gene expression was further confirmed at the protein level in the gut wash. Synbiotic supplementation also positively impacted the microbiota composition in both the small and large intestines, resulting in higher proportions of Bifidobacterium genus, among others. In addition, there was an increase in butanoic, isobutanoic, and acetic acid concentrations in the cecum but a reduction in the small intestine. At the systemic level, synbiotic supplementation resulted in higher levels of immunoglobulin IgG2c in plasma, SG, and MLN, but it did not modify the main lymphocyte subsets in the spleen and MLN. Overall, synbiotic maternal supplementation is able to positively influence the immune system development and microbiota of the suckling offspring, particularly at the gastrointestinal level.

Breast milk immune composition varies during the transition stage of lactation: characterization of immunotypes in the MAMI cohort.

Background: Breast milk is a complex and dynamic fluid needed for infant development and protection due to its content of bioactive factors such as immunoglobulins (Igs). Most studies focus primarily on IgA, but other types of Ig and even other immune components (cytokines and adipokines) may also play significant roles in neonatal health. As a first step, we aimed to characterize the Ig profile, many cytokines, and two adipokines (leptin and adiponectin) at two sampling time points within the transitional stage, which is the least studied phase in terms of these components. The secondary objective was to identify different breast milk immunotypes in the MAMI cohort substudy, and finally, we further aimed at analyzing maternal and infant characteristics to identify influencing factors of breast milk immune composition. Methods: Breast milk samples from 75 mothers were studied between days 7 and 15 postpartum. The Igs, cytokines, and adipokine levels were determined by a multiplex approach, except for the IgA, IgM, and leptin that were evaluated by ELISA. Results: IgA, IgM, IgE, IgG2, IL-1ß, IL-5, IL-6, IL-10, and IL-17 were significantly higher on day 7 with respect to day 15. The multiple factor analysis (MFA) allowed us to identify two maternal clusters (immunotypes) depending on the breast milk immune profile evolution from day 7 to day 15, mainly due to the IgE and IgG subtypes, but not for IgA and IgM, which always presented higher levels early in time. Conclusion: All these results demonstrated the importance of the dynamics of the breast milk composition in terms of immune factors because even in the same lactation stage, a difference of 1 week has induced changes in the breast milk immune profile. Moreover, this immune profile does not evolve in the same way for all women. The dynamic compositional changes may be maternal-specific, as we observed differences in parity and exclusive breastfeeding between the two BM immunotype groups, which could potentially impact infant health.

Changes in prescription drug abuse during the COVID-19 pandemic evidenced in the Catalan pharmacies.

Introduction: The impact of a pandemic on the mental health of the population is to be expected due to risk factors such as social isolation. Prescription drug abuse and misuse could be an indicator of the impact of the COVID-19 pandemic on mental health. Community pharmacists play an important role in addressing prescription drug abuse by detecting signs and behaviors that give a clearer indication that a drug abuse problem exists. Methods: A prospective observational study to observe prescription drug abuse was conducted from March 2020 to December 2021 to compare with data obtained in the previous 2 years, through the Medicine Abuse Observatory, the epidemiological surveillance system set up in Catalonia. Information was obtained through a validated questionnaire attached on a web-based system and data collection software. A total of 75 community pharmacies were enrolled in the program. Results: The number of notifications during the pandemic period (11.8/100.000 inhabitants) does not indicate a significant change compared with those from pre-pandemic period, when it was 12.5/100.000 inhabitants. However, the number of notifications during the first wave when lockdown was in place stood at 6.1/100,000 inhabitants, significantly lower than in both the pre-pandemic and the whole of the pandemic periods. Regarding the patient's profile, it was observed that the proportion of younger patients (<25 and 25-35) rose in contrast to older ones (45-65 and >65). The use of benzodiazepines and fentanyl increased. Conclusions: This study has made it possible to observe the impact of the pandemic caused by COVID-19 on the behavior of patients in terms of use of prescription drugs through analysis of the trends of abuse or misuse and by comparing them with the pre-pandemic period. Overall, the increased detection of benzodiazepines has pointed out stress and anxiety generated by the pandemic.

Creation and Implementation of a New Sentinel Surveillance Model in Pharmacy Offices in Southern Europe.

Traditionally, health sentinel networks have focused on the reporting of data by primary care physicians and hospitals, ignoring the role of the community pharmacist as an expert in drugs. The objective of this study was to describe a method for creating a network of sentinel pharmacies in a region of Southern Europe in order to have a pharmaceutical surveillance system that is representative of the territory to be monitored and that can respond to any events or incidents that can be followed up by the community pharmacy. The creation process was carried out in three phases: a first phase of selection through a cluster and population analysis and a final adjustment, a second phase of voluntariness and random selection, and a third phase of training and implementation of the network. A sentinel network of 75 community pharmacies has been established in Catalonia. The network monitors 2.47% of the total population with a homogeneous proportion of urban (42), rural (30), and mountain-area (3) pharmacies based on the particular characteristics of the territory. This model allows increased surveillance in the territory, objectively and representatively detects problems arising from the use of medicines, and establishes improvement strategies of public health.

Evaluation of Medicine Abuse Trends in Community Pharmacies: The Medicine Abuse Observatory (MAO) in a Region of Southern Europe.

The misuse of medicines is a global public health concern that needs to be taken into consideration and requires actions across all government sectors and society. The aim of this study is to identify trends of drug abuse in Catalonia, a region of Spain located in the South of Europe. For this purpose, a questionnaire-based detection tool was created and implemented in 60 community pharmacies. Out of 548 questionnaires (98.4%), 64.2% of participants were men and the highest age proportion was 25-35 years (31.4%). Potential drug abuse was the highest in urban pharmacies (84.9%). The main drug class involved were benzodiazepines (31.8%), codeine (19.3%), tramadol (7.5%), methylphenidate (5.8%), gabapentinoids (5.8%), cycloplegic drops (4.4%), z-drugs (2.6%), piracetam (2.2%), dextromethorphan (1.6%) and clomethiazole (1.1%). The majority of drugs were requested without prescription (58.6%) and through probably forged prescriptions (23.7%). Slightly less than half (49.8%) of the patients request frequently to the pharmacist, especially in rural and mountain pharmacies (73.3% and 88.5%, respectively). A small proportion (10.8%) were requested with intimidation. Pharmacists only supplied in 21.7% of the cases. This study has demonstrated the suitability of the new detection system, being a useful approach to replicate in other locations with similar needs.

Association of Maternal Microbiota and Diet in Cord Blood Cytokine and Immunoglobulin Profiles.

Mothers confer natural passive immunization to their infants through the transplacental pathway during the gestation period. The objective of the present study was to establish at birth the maternal and cord plasma concentration and relationship of immunoglobulins (Igs), cytokines (CKs), and adipokines. In addition, the impact of the maternal microbiota and diet was explored. The plasma profile of these components was different between mothers and babies, with the levels of many CKs, IgM, IgG2a, IgE, IgA, and leptin significantly higher in mothers than in the cord sample. Moreover, the total Igs, all IgG subtypes, IgE, and the Th1/Th2 ratio positively correlated in the mother-infant pair. Maternal dietary components such as monounsaturated fatty acids-polyunsaturated fatty acids and fiber were positively associated with some immune factors such as IgA in cord samples. The microbiota composition clustering also influenced the plasma profile of some factors (i.e., many CKs, some Ig, and adiponectin). In conclusion, we have established the concentration of these immunomodulatory factors in the maternal-neonatal pair at birth, some positive associations, and the influence of maternal diet and the microbiota composition, suggesting that the immune status during pregnancy, in terms of CKs and Igs levels, can influence the immune status of the infant at birth.

The Immature Gut Barrier and Its Importance in Establishing Immunity in Newborn Mammals.

The gut is an efficient barrier which protects against the passage of pathogenic microorganisms and potential harmful macromolecules into the body, in addition to its primary function of nutrient digestion and absorption. Contrary to the restricted macromolecular passage in adulthood, enhanced transfer takes place across the intestines during early life, due to the high endocytic capacity of the immature intestinal epithelial cells during the fetal and/or neonatal periods. The timing and extent of this enhanced endocytic capacity is dependent on animal species, with a prominent non-selective intestinal macromolecular transfer in newborn ungulates, e.g., pigs, during the first few days of life, and a selective transfer of mainly immunoglobulin G (IgG), mediated by the FcRn receptor, in suckling rodents, e.g., rats and mice. In primates, maternal IgG is transferred during fetal life via the placenta, and intestinal macromolecular transfer is largely restricted in human neonates. The period of intestinal macromolecular transmission provides passive immune protection through the transfer of IgG antibodies from an immune competent mother; and may even have extra-immune beneficial effects on organ maturation in the offspring. Moreover, intestinal transfer during the fetal/neonatal periods results in increased exposure to microbial and food antigens which are then presented to the underlying immune system, which is both naïve and immature. This likely stimulates the maturation of the immune system and shifts the response toward tolerance induction instead of activation or inflammation, as usually seen in adulthood. Ingestion of mother's milk and the dietary transition to complex food at weaning, as well as the transient changes in the gut microbiota during the neonatal period, are also involved in the resulting immune response. Any disturbances in timing and/or balance of these parallel processes, i.e., intestinal epithelial maturation, luminal microbial colonization and mucosal immune maturation due to, e.g., preterm birth, infection, antibiotic use or nutrient changes during the neonatal period, might affect the establishment of the immune system in the infant. This review will focus on how differing developmental processes in the intestinal epithelium affect the macromolecular passage in different species and the possible impact of such passage on the establishment of immunity during the critical perinatal period in young mammals.

Microorganismos propios y cómo nos defienden (parte II): probióticos y sistema inmunitario / No disponible

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Microorganismos propios y cómo nos defienden (parte I): Microbiota y sistema inmunitario / No disponible

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Preventive Effect of a Synbiotic Combination of Galacto- and Fructooligosaccharides Mixture With Bifidobacterium breve M-16V in a Model of Multiple Rotavirus Infections.

Rotavirus (RV) causes morbidity and mortality among infants worldwide, and there is evidence that probiotics and prebiotics can have a positive influence against infective processes such as that due to RV. The aim of this study was to evidence a preventive role of one prebiotic mixture (of short-chain galactooligosaccharide/long-chain fructooligosaccharide), the probiotic Bifidobacterium breve M-16V and the combination of the prebiotic and the probiotic, as a synbiotic, in a suckling rat double-RV infection model. Hyperimmune bovine colostrum was used as protection control. The first infection was induced with RV SA11 and the second one with EDIM. Clinical variables and immune response were evaluated after both infections. Dietary interventions ameliorated clinical symptoms after the first infection. The prebiotic and the synbiotic significantly reduced viral shedding after the first infection, but all the interventions showed higher viral load than in the RV group after the second infection. All interventions modulated ex vivo antibody and cytokine production, gut wash cytokine levels and small intestine gene expression after both infections. In conclusion, a daily supplement of the products tested in this preclinical model is highly effective in preventing RV-induced diarrhea but allowing the boost of the early immune response for a future immune response against reinfection, suggesting that these components may be potential agents for modulating RV infection in infants.

Effect of virgin olive oil and thyme phenolic compounds on blood lipid profile: implications of human gut microbiota.

PURPOSE: To investigate the effect of virgin olive oil phenolic compounds (PC) alone or in combination with thyme PC on blood lipid profile from hypercholesterolemic humans, and whether the changes generated are related with changes in gut microbiota populations and activities. METHODS: A randomized, controlled, double-blind, crossover human trial (n = 12) was carried out. Participants ingested 25 mL/day for 3 weeks, preceded by 2-week washout periods, three raw virgin olive oils differing in the concentration and origin of PC: (1) a virgin olive oil (OO) naturally containing 80 mg PC/kg, (VOO), (2) a PC-enriched virgin olive oil containing 500 mg PC/kg, from OO (FVOO), and (3) a PC-enriched virgin olive oil containing a mixture of 500 mg PC/kg from OO and thyme, 1:1 (FVOOT). Blood lipid values and faecal quantitative changes in microbial populations, short chain fatty acids, cholesterol microbial metabolites, bile acids, and phenolic metabolites were analysed. RESULTS: FVOOT decreased seric ox-LDL concentrations compared with pre-FVOOT, and increased numbers of bifidobacteria and the levels of the phenolic metabolite protocatechuic acid compared to VOO (P < 0.05). FVOO did not lead to changes in blood lipid profile nor quantitative changes in the microbial populations analysed, but increased the coprostanone compared to FVOOT (P < 0.05), and the levels of the faecal hydroxytyrosol and dihydroxyphenylacetic acids, compared with pre-intervention values and to VOO, respectively (P < 0.05). CONCLUSION: The ingestion of a PC-enriched virgin olive oil, containing a mixture of olive oil and thyme PC for 3 weeks, decreases blood ox-LDL in hypercholesterolemic humans. This cardio-protective effect could be mediated by the increases in populations of bifidobacteria together with increases in PC microbial metabolites with antioxidant activities.

Preclinical Immunomodulation by the Probiotic Bifidobacterium breve M-16V in Early Life.

This study aimed to investigate the effect of supplementation with the probiotic Bifidobacterium breve M-16V on the maturation of the intestinal and circulating immune system during suckling. In order to achieve this purpose, neonatal Lewis rats were supplemented with the probiotic strain from the 6th to the 18th day of life. The animals were weighed during the study, and faecal samples were obtained and evaluated daily. On day 19, rats were euthanized and intestinal wash samples, mesenteric lymph node (MLN) cells, splenocytes and intraepithelial lymphocytes (IEL) were obtained. The probiotic supplementation in early life did not modify the growth curve and did not enhance the systemic immune maturation. However, it increased the proportion of cells bearing TLR4 in the MLN and IEL, and enhanced the percentage of the integrin αEß7+ and CD62L+ cells in the MLN and that of the integrin αEß7+ cells in the IEL, suggesting an enhancement of the homing process of naïve T lymphocytes to the MLN, and the retention of activated lymphocytes in the intraepithelial compartment. Interestingly, B. breve M-16V enhanced the intestinal IgA synthesis. In conclusion, supplementation with the probiotic strain B. breve M-16V during suckling improves the development of mucosal immunity in early life.

Influence of Phenol-Enriched Olive Oils on Human Intestinal Immune Function.

Olive oil (OO) phenolic compounds (PC) are able to influence gut microbial populations and metabolic output. Our aim was to investigate whether these compounds and changes affect the mucosal immune system. In a randomized, controlled, double blind cross-over human trial, for three weeks, preceded by two-week washout periods, 10 hypercholesterolemic participants ingested 25 mL/day of three raw virgin OO differing in their PC concentration and origin: (1) an OO containing 80 mg PC/kg (VOO); (2) a PC-enriched OO containing 500 mg PC/kg from OO (FVOO); and (3) a PC-enriched OO containing a mixture of 500 mg PC/kg from OO and thyme (1:1, FVOOT). Intestinal immunity (fecal immunoglobulin A (IgA) and IgA-coated bacteria) and inflammation markers (C-reactive protein (CRP) and fecal interleukin 6 (IL-6), tumor necrosis factor α (TNFα) and calprotectin) was analyzed. The ingestion of high amounts of OO PC, as contained in FVOO, tended to increase the proportions of IgA-coated bacteria and increased plasma levels of CRP. However, lower amounts of OO PC (VOO) and the combination of two PC sources (FVOOT) did not show significant effects on the variables investigated. Results indicate a potential stimulation of the immune system with very high doses of OO PC, which should be further investigated.