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Background: Since 2008, several cases of pregabalin abuse have been reported to the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). Despite this evidence, gabapentinoids are increasingly being prescribed. Moreover, pregabalin is being used in a recreational setting for its dissociative effects and euphoria. Objectives: To assess the characteristics of non-therapeutic users of pregabalin and to show behavioral trends associated with requests for the medicine at community pharmacies. Methods: The Medicine Abuse Observatory (MAO), an epidemiological surveillance system, was able to analyze trends about the most diverted drugs and the behavioral patterns of the population from community pharmacies. We have conducted an observational and cross-sectional study from January 2022 to April 2023, to determinate trends in the behavior of patients who have requested pregabalin in the Catalan Sephanet. Results: Behavior with respect to sex was similar in all health problems, although one difference was raised when considering neuropathic pain, in which the females were more involved (72.7%), especially around 2.5 times more than the males (27.3%, p < 0.05). The study showed a potential recreational use related to patients aged <25 years and patients aged 25–35 years (p < 0.05). Neuropathic pain was mainly identified in patients >65 years. In 75% of the cases, there was a preceding prescription. Conclusions: This study underlines the evidence of non-therapeutic use of pregabalin among the Catalan population and the need to take control measures. Actions should be promoted, both at the level of prescription and dispensing, and focusing on education and knowledge about the risks that may appear with the use of pregabalin. [ABSTRACT FROM AUTHOR]

Maternal breast milk plays a key role in providing newborns with passive immunity and stimulating the maturation of an infant's immune system, protecting them from many diseases. It is known that diet can influence the immune system of lactating mothers and the composition of their breast milk. The aim of this study was to establish if a supplementation during the gestation and lactation of Lewis rats with extra virgin olive oil (EVOO), due to the high proportion of antioxidant components in its composition, has an impact on the mother's immune system and on the breast milk's immune composition. For this, 10 mL/kg of either EVOO, refined oil (control oil) or water (REF group) were orally administered once a day to rats during gestation and lactation periods. Immunoglobulin (Ig) concentrations and gene expressions of immune molecules were quantified in several compartments of the mothers. The EVOO group showed higher IgA levels in both the breast milk and the mammary glands than the REF group. In addition, the gene expression of IgA in mammary glands was also boosted by EVOO consumption. Overall, EVOO supplementation during gestation and lactation is safe and does not negatively affect the mother's immune system while improving breast milk immune composition by increasing the presence of IgA, which could be critical for an offspring's immune health. [ABSTRACT FROM AUTHOR]

Rotavirus (RV) infection is a major cause of acute gastroenteritis in children under 5 years old, resulting in elevated mortality rates in low-income countries. The efficacy of anti-RV vaccines is limited in underdeveloped countries, emphasizing the need for novel strategies to boost immunity and alleviate RV-induced diarrhea. This study explores the effectiveness of interventions involving extracellular vesicles (EVs) from probiotic and commensal E. coli in mitigating diarrhea and enhancing immunity in a preclinical model of RV infection in suckling rats. On days 8 and 16 of life, variables related to humoral and cellular immunity and intestinal function/architecture were assessed. Both interventions enhanced humoral (serum immunoglobulins) and cellular (splenic natural killer (NK), cytotoxic T (Tc) and positive T-cell receptor γδ (TCRγδ) cells) immunity against viral infections and downregulated the intestinal serotonin receptor-3 (HTR3). However, certain effects were strain-specific. EcoR12 EVs activated intestinal CD68, TLR2 and IL-12 expression, whereas EcN EVs improved intestinal maturation, barrier properties (goblet cell numbers/mucin 2 expression) and absorptive function (villus length). In conclusion, interventions involving probiotic/microbiota EVs may serve as a safe postbiotic strategy to improve clinical symptoms and immune responses during RV infection in the neonatal period. Furthermore, they could be used as adjuvants to enhance the immunogenicity and efficacy of anti-RV vaccines. [ABSTRACT FROM AUTHOR]

The Mediterranean diet (MD) is very rich in bioactive and immunomodulatory components. Some of these have demonstrated their protective activity in inflammation. The objective of this study was to evaluate the impact of a diet rich in fiber and polyphenols on an inflammatory process. The intervention was performed in two groups of 7-week-old rats, one receiving an experimental MD-like diet and another fed a reference diet (REF). At the end of the study, local inflammation was induced by injecting the rat's paw with carrageenan. A lower paw volume was observed in = rats from the MD-like diet group. [ABSTRACT FROM AUTHOR]

This study aimed to characterize two Peruvian cocoa populations (CCN51 and JL2) and determine their influence on rat metabolism. For this, the phytochemical composition and in vitro antioxidant activity of CCN51 and JL2 were established. Furthermore, Wistar rats were fed with either CCN51-, JL2-enriched or standard diets for 4 weeks. At the end, an oral glucose tolerance test was carried out. Moreover, visceral adiposity index and fecal pH were measured. The JL2 cocoa showed the highest content of total polyphenols, catechin and epigallocatechin-3-gallate as well as the highest in vitro antioxidant activity. No significant differences were observed in glycemia among the three experimental groups, but both cocoa-fed groups showed lower visceral adiposity than the standard diet-fed animals. Lower fecal pH was observed after both cocoa diets. In conclusion, two Peruvian cocoa populations with different polyphenol compositions induced similar effects on rat metabolism when administered as 10% of the diet for 4 weeks. [ABSTRACT FROM AUTHOR]

Maternal diet during lactation, pregnancy or even before can influence the health of the baby. The Mediterranean diet is the one with the highest level of evidence due to its richness in fiber and polyphenols, among other bioactive components. This study investigated the impact of a diet rich in fiber and polyphenols (HFP diet) supplemented during pregestation, gestation, and lactation at the intestinal level in both dams and their offspring. This diet had an intestinal impact in both pregnant rats and their offspring in terms of intestinal growth. Further research is required to elucidate the underlying mechanisms involved. [ABSTRACT FROM AUTHOR]

Microbiota–host communication is primarily achieved by secreted factors that can penetrate the mucosal surface, such as extracellular membrane vesicles (EVs). The EVs released by the gut microbiota have been extensively studied in cellular and experimental models of human diseases. However, little is known about their in vivo effects in early life, specifically regarding immune and intestinal maturation. This study aimed to investigate the effects of daily administration of EVs from probiotic and commensal E. coli strains in healthy suckling rats during the first 16 days of life. On days 8 and 16, we assessed various intestinal and systemic variables in relation to animal growth, humoral and cellular immunity, epithelial barrier maturation, and intestinal architecture. On day 16, animals given probiotic/microbiota EVs exhibited higher levels of plasma IgG, IgA, and IgM and a greater proportion of Tc, NK, and NKT cells in the spleen. In the small intestine, EVs increased the villi area and modulated the expression of genes related to immune function, inflammation, and intestinal permeability, shifting towards an anti-inflammatory and barrier protective profile from day 8. In conclusion, interventions involving probiotic/microbiota EVs may represent a safe postbiotic strategy to stimulate immunity and intestinal maturation in early life. [ABSTRACT FROM AUTHOR]

Viral infections are described as modifying host gene expression; however, there is limited insight regarding rotavirus (RV) infections. This study aimed to assess the changes in intestinal gene expression after RV infection in a preclinical model, and the effect of 2-fucosyllactose (2′-FL) on this process. From days 2 to 8 of life, rats were supplemented with the dietary oligosaccharide 2′-FL or vehicle. In addition, an RV was inoculated on day 5 to nonsupplemented animals (RV group) and to 2′-FL-fed animals (RV+2′-FL group). Incidence and severity of diarrhea were established. A portion from the middle part of the small intestine was excised for gene expression analysis by microarray kit and qPCR. In nonsupplemented animals, RV-induced diarrhea upregulated host antiviral genes (e.g., Oas1a, Irf7, Ifi44, Isg15) and downregulated several genes involved in absorptive processes and intestinal maturation (e.g., Onecut2, and Ccl19). The 2′-FL-supplemented and infected animals had less diarrhea; however, their gene expression was affected in a similar way as the control-infected animals, with the exception of some immunity/maturation markers that were differentially expressed (e.g., Ccl12 and Afp). Overall, assessing the expression of these key genes may be useful in the evaluation of the efficacy of nutritional interventions or treatments for RV infection. [ABSTRACT FROM AUTHOR]

The Third International Electronic Conference on Nutrients—Precision Nutrition and Nutrigenomics took place from November 1 to 15, 2023. The conference focused on precision nutrition, which involves tailoring dietary approaches to an individual's genetic and epigenetic information, age, gender, lifestyle, gut microbiota, and health status. The event brought together researchers, clinicians, and experts from around the world to discuss new discoveries and future directions in this field. The conference featured sessions on topics such as the role of gut microbiota, epigenetics, nutriomics, and genetic polymorphisms in precision nutrition. The conference organizers expressed gratitude to the sponsors and media partners involved. [Extracted from the article]

Stressful situations such as a high-intensity exercise or exhausting training programs can act as immune disruptors leading to transitory immunodepression status, which can be accompanied by alterations of the gastrointestinal functions. Hesperidin intake has demonstrated ergogenic activity and is able to influence the intestinal ecosystem and immunity. We aimed to investigate the effect of hesperidin consumption in rats submitted to an intense training and a final exhaustion test, focusing on the functionality of the intestinal immune system and on the cecal microbiota. Rats, supplemented or not with hesperidin, were intensively trained on a treadmill for 5 weeks. Samples were obtained 24 h after a regular training session, and immediately and 24 h after a final exhaustion test. Cecal microbiota and composition and function of mesenteric lymph node (MLN) lymphocytes and mucosal immunoglobulin A (IgA) were determined. Results showed that chronic intense exercise followed by an exhausting test induced changes in the intestinal immune compartment such as the distribution and function of MLN lymphocytes. Although the hesperidin supplementation did not prevent these alterations, it was able to enhance IgA synthesis in the intestinal compartment. This could be important in enhancing the immune intestinal barrier in this stressful situation. [ABSTRACT FROM AUTHOR]

The aim of this study was to establish the influence of flavonoid-enriched diets on the immune alterations induced by an intensive training and a final exhaustion test in rats. A flavanol-enriched diet (with 10% cocoa, C10 diet) and a flavanol and flavanone-enriched diet (C10 plus 0.5% hesperidin, CH diet) were used. Lewis rats were fed either a standard diet, C10 diet or CH diet while they were submitted to an intensive running training on a treadmill. After 6 weeks, samples were obtained 24 h after performing a regular training (T groups) and after carrying out a final exhaustion test (TE groups). The C10 diet attenuated the increase in plasma cortisol induced by exhaustion, while both the C10 and the CH diets prevented the alterations in the spleen Th cell proportion. The experimental diets also induced an increase in serum immunoglobulin concentration and an enhancement of spleen natural killer cytotoxicity, which may be beneficial in situations with a weakened immunity. Most of the effects observed in the CH groups seem to be due to the cocoa content. Overall, a dietary intervention with flavonoids enhances immune function, partially attenuating the alterations in systemic immunity induced by intensive training or exhausting exercise. [ABSTRACT FROM AUTHOR]

Galectins (Gal) are a family of conserved soluble proteins with high affinity for β-galactoside structures. They have been recognized as important proteins for successful pregnancy. However, little is known about their presence in breast milk and their role in early infancy. Gal-1, -3 and -9 concentrations were evaluated by Multiplex immunoassays in mother–infant pairs from the MAMI cohort in maternal plasma (MP) (n = 15) and umbilical cord plasma (UCP) (n = 15) at birth and in breast milk samples (n = 23) at days 7 and 15 postpartum. Data regarding mother and infant characteristics were collected. Gal-9 was present in a lower concentration range than Gal-1 and Gal-3 in plasma, specifically in UCP. A major finding in the current study is that Gal-1, -3 and -9 were detected for the first time in all the transitional breast milk samples and no differences were found when comparing the two breastfeeding time points. Finally, Gal levels were associated with some maternal and infant characteristics, such as gestational age, pregnancy weight gain, maternal diet, the gender, infant growth and infant infections. In conclusion, Gal levels seem to be involved in certain developmental aspects of early life. [ABSTRACT FROM AUTHOR]

The digestion of gluten generates toxic peptides, among which a highly immunogenic proline-rich 33-mer from wheat α-gliadin, that trigger coeliac disease. Neprosin from the pitcher plant is a reported prolyl endopeptidase. Here, we produce recombinant neprosin and its mutants, and find that full-length neprosin is a zymogen, which is self-activated at gastric pH by the release of an all-β pro-domain via a pH-switch mechanism featuring a lysine plug. The catalytic domain is an atypical 7+8-stranded β-sandwich with an extended active-site cleft containing an unprecedented pair of catalytic glutamates. Neprosin efficiently degrades both gliadin and the 33-mer in vitro under gastric conditions and is reversibly inactivated at pH > 5. Moreover, co-administration of gliadin and the neprosin zymogen at the ratio 500:1 reduces the abundance of the 33-mer in the small intestine of mice by up to 90%. Neprosin therefore founds a family of eukaryotic glutamate endopeptidases that fulfils requisites for a therapeutic glutenase. Celiac disease is characterized by intolerance to gluten, a cereal protein. Here, the authors show that neprosin, a glutamate peptidase from the pitcher plant, efficiently cleaves gluten components under physiological conditions in vitro and in the gut of mice. [ABSTRACT FROM AUTHOR]

The article offers information on various aspects of nutrition and nutritional sciences, focusing on the diet-disease relationship, nutrition during pregnancy, and the use of dietary supplements.

Modern hyperprolific sows must deal with large litters (16–20 piglets) which reduce piglet birthweight with a concomitant increase in the proportion of small and intrauterine growth retarded piglets. However, larger litters do not only have a greater variation of piglet weights, but also a greater variation in colostrum and milk consumption within the litter. To further understand the impact that body weight has on piglets, the present study aimed to evaluate the degree of physiological weakness of the smallest piglets at birth and during the suckling period (20 d) compared to their middle-weight littermates through their jejunal gene expression. At birth, light piglets showed a downregulation of genes related to immune response (FAXDC2 , HSPB1 , PPARGC1α), antioxidant enzymes (SOD2m), digestive enzymes (ANPEP, IDO1, SI), and nutrient transporter (SLC39A4) (P < 0.05) but also a tendency for a higher mRNA expression of GBP1 (inflammatory regulator) and HSD11β1 (stress hormone) genes compared to their heavier littermates (P < 0.10). Excluding HSD11β1 gene, all these intestinal gene expression differences initially observed at birth between light and middle-weight piglets were stabilized at the end of the suckling period, when others appeared. Genes involved in barrier function (CLDN1), pro-inflammatory response (CXCL2, IL6, IDO1), and stress hormone signaling (HSD11β1) over-expressed compared to their middle-weight littermates (P < 0.05). In conclusion, at birth and at the end of suckling period, light body weight piglets seem to have a compromised gene expression and therefore impaired nutrient absorption, immune and stress responses compared to their heavier littermates. [ABSTRACT FROM AUTHOR]

The leading cause of gastroenteritis among young children worldwide is the Group A rotaviruses (RV), which produce a wide range of symptoms, from a limited diarrhea to severe dehydration and even death. After an RV infection, immunity is not complete and less severe re-infections usually occur. These infections could be ameliorated by nutritional interventions with bioactive compounds, such as prebiotics. The aim of this research was to study the impact of a particular galactooligosaccharide (B-GOS) on the RV symptomatology and immune response during two consecutive infections. Lewis neonatal rats were inoculated with SA11 (first RV infection) on day 6 of life and with EDIM (second RV infection) on day 17 of life. B-GOS group was administered by oral gavage with a daily dose of B-GOS between days three to nine of life. Clinical and immunological variables were assessed during both infective processes. In the first infection, after the prebiotic intervention with B-GOS, a lower incidence, duration, and overall severity of the diarrhea (p < 0.05) was observed. In addition, it improved another severity indicator, the fecal weight output, during the diarrhea period (p < 0.05). The second RV infection failed in provoking diarrhea in the groups studied. The immune response during first infection with SA11 was not affected by B-GOS administration and had no impact on second infection, but the prebiotic intervention significantly increased IFN-γ and TNF-α intestinal production after the second infection (p < 0.05). In summary, B-GOS supplementation is able to reduce the incidence and severity of the RV-associated diarrhea and to influence the immune response against RV infections. [ABSTRACT FROM AUTHOR]

Background: Breast milk is a vehicle to transfer protective antibodies from the lactating mother to the neonate. After SARS-CoV-2 infection, virus-specific IgA and IgG have been identified in breast milk, however, there are limited data on the impact of different COVID-19 vaccine types in lactating women. This study is aimed to evaluate the time course of induction of SARS-CoV-2-specific IgA and IgG in breast milk after vaccination. Methods: In this prospective observational study in Spain, 86 lactating women from priority groups receiving the vaccination against SARS-CoV-2 were included. Breast milk samples were collected longitudinally at seven or eight-time points (depending on vaccine type). A group with confirmed SARS-CoV-2 infection (n=19) and a group of women from pre-pandemic time (n=20) were included for comparison. Results: Eighty-six vaccinated lactating women [mean age, 34.6 ± 3.7 years] of whom 96% were Caucasian and 92% were healthcare workers. A total number of 582 milk samples were included, and vaccine distribution was BioNTech/Pfizer (BNT162b2, n=34), Moderna (mRNA-1273, n=20), and AstraZeneca (ChAdOx1 nCoV-19, n=32). For each vaccine, 7 and 8 longitudinal time points were collected from baseline up to 30 days after the second dose for mRNA vaccines and adenovirus-vectored vaccines, respectively. A strong reactivity was observed for IgG and IgA after vaccination mainly after the 2nd dose. The presence and persistence of specific SARS-CoV-2 antibodies in breast milk were dependent on the vaccine type, with higher IgG and IgA levels in mRNA-based vaccines when compared to AstraZeneca, and on previous virus exposure. High intra- and inter-variability were observed, being relevant for IgA antibodies. In milk from vaccinated women, anti-SARS-CoV-2 IgG was significantly higher while IgA levels were lower than in milk from COVID-19-infected women. Women with previous COVID-19 increased their IgG antibodies levels after the first dose to a similar level observed in vaccinated women after the second dose. Conclusions: COVID-19 vaccination induced anti-SARS-CoV-2 IgA and IgG in breast milk with higher levels after the 2nd dose. Levels of anti-SARS-CoV-2 IgA and IgG are dependent on the vaccine type. Further studies are warranted to demonstrate the protective antibody effect against COVID-19 in infants from vaccinated and infected mothers. Trial registration: NCT04751734 (date of registration is on February 12, 2021) [ABSTRACT FROM AUTHOR]

Intensive acute exercise can induce oxidative stress, leading to muscle damage and immune function impairment. Cocoa diet could prevent this oxidative stress and its consequences on immunity. Our aim was to assess the effect of a cocoa-enriched diet on the reactive oxygen species (ROS) production by peritoneal macrophages, blood immunoglobulin (Ig) levels, leukocyte counts, and the physical performance of rats submitted to an intensive acute exercise, as well as to elucidate the involvement of cocoa fiber in such effects. For this purpose, Wistar rats were fed either a standard diet, i.e., a diet containing 10% cocoa (C10), or a diet containing 5% cocoa fiber (CF) for 25 days. Then, half of the rats of each diet ran on a treadmill until exhaustion, and 16 h later, the samples were obtained. Both C10 and CF diets significantly prevented the increase in ROS production. However, neither the cocoa diet or the cocoa fiber-enriched diet prevented the decrease in serum IgG induced by acute exercise. Therefore, although the cocoa-enriched diet was able to prevent the excessive oxidative stress induced by intensive exercise, this was not enough to avoid the immune function impairment due to exercise. [ABSTRACT FROM AUTHOR]

Rotavirus (RV) is the main cause of gastroenteritis in children. Prebiotics and, more recently, postbiotics are used for preventing and treating gastrointestinal infections. The aim of this study was to analyze the effects of a LactofidusTM, short-chain galacto-oligosaccharides (scGOS) and long-chain fructo-oligosaccharides (lcFOS) mixture, and their combination on RV infection, in a rat model, for early life diarrhea. Fifteen litters of suckling rats were intragastrically administered daily with the vehicle, the prebiotic mixture, the postbiotic or the combination. The RV was inoculated on day 5 and then fecal samples were clinically evaluated daily. Viral shedding, intestinal permeability assay, in vitro blocking assay, immunoglobulin profiles, and anti-RV response were assessed at day 8 and 16 of life. Cecal microbiota composition, intestinal gene expression, and short chain fatty acids (SCFAs) were analyzed at day 16. The incidence and severity of diarrhea were significantly reduced by all the supplementations. Moreover, they showed blocking activity, changes in the immunoglobulin profiles, in gut microbiota, and in the intestinal gene expression. The prebiotic mixture reduced gut permeability and changed the SCFA profile, whereas the postbiotic enhanced the expression of Toll-like receptors (TLRs). The combination preserved most of the individual observed effects, and furthermore, complementary effects, such as an increase in white blood cells and lymphocytes recruitment, as well as upregulation of TLR7 and TLR9 gene expression. [ABSTRACT FROM AUTHOR]

Objectives: To develop and validate a specific protocol for SARS-CoV-2 detection in breast milk matrix and to determine the impact of maternal SARS-CoV-2 infection on the presence, concentration and persistence of specific SARS-CoV-2 antibodies.Design and Patients: This is a prospective, multicentre longitudinal study (April-December 2020) in 60 mothers with SARS-CoV-2 infection and/or who have recovered from COVID-19. A control group of 13 women before the pandemic were also included.Setting: Seven health centres from different provinces in Spain.Main Outcome Measures: Presence of SARS-CoV-2 RNA in breast milk, targeting the N1 region of the nucleocapsid gene and the envelope (E) gene; presence and levels of SARS-CoV-2-specific immunoglobulins (Igs)-IgA, IgG and IgM-in breast milk samples from patients with COVID-19.Results: All breast milk samples showed negative results for presence of SARS-CoV-2 RNA. We observed high intraindividual and interindividual variability in the antibody response to the receptor-binding domain of the SARS-CoV-2 spike protein for each of the three isotypes IgA, IgM and IgG. Main Protease (MPro) domain antibodies were also detected in milk. 82.9% (58 of 70) of milk samples were positive for at least one of the three antibody isotypes, with 52.9% of these positive for all three Igs. Positivity rate for IgA was relatively stable over time (65.2%-87.5%), whereas it raised continuously for IgG (from 47.8% for the first 10 days to 87.5% from day 41 up to day 206 post-PCR confirmation).Conclusions: Our study confirms the safety of breast feeding and highlights the relevance of virus-specific SARS-CoV-2 antibody transfer. This study provides crucial data to support official breastfeeding recommendations based on scientific evidence. Trial registration number NCT04768244. [ABSTRACT FROM AUTHOR]

The aim of the present study was to evaluate the effect of trace mineral nutrition on sow performance, mineral content, and intestinal gene expression of neonate piglets when inorganic mineral sources (ITM) were partially replaced by their organic mineral (OTM) counterparts. At 35 d postmating, under commercial conditions, a total of 240 hyperprolific multiparous sows were allocated into three experimental diets: 1) ITM: with Zn, Cu, and Mn at 80, 15, and 60 mg/kg, respectively; 2) partial replacement trace mineral source (Replace): with a 30 % replacement of ITM by OTM, resulting in ITM + OTM supplementation of Zn (56 + 24 mg/kg), Cu (10.5 + 4.5 mg/kg), and Mn (42 + 18 mg/kg); and 3) Reduce and replace mineral source (R&R): reducing a 50% of the ITM source of Zn (40 + 24 mg/kg), Cu (7.5 + 4.5 mg/kg), and Mn (30 + 18 mg/kg). At farrowing, 40 piglets were selected, based on birth weight (light: <800 g, and average: >1,200 g), for sampling. Since the present study aimed to reflect results under commercial conditions, it was difficult to get an equal parity number between the experimental diets. Overall, no differences between experimental diets on sow reproductive performance were observed. Light piglets had a lower mineral content (P < 0.05) and a downregulation of several genes (P < 0.10) involved in physiological functions compared with their average littermates. Neonate piglets born from Replace sows had an upregulation of genes involved in functions like immunity and gut barrier, compared with those born from ITM sows (P < 0.10), particularly in light piglets. In conclusion, the partial replacement of ITM by their OTM counterparts represents an alternative to the totally inorganic supplementation with improvements on neonate piglet gene expression, particularly in the smallest piglets of the litter. The lower trace mineral storage together with the greater downregulation of gut health genes exposed the immaturity and vulnerability of small piglets. [ABSTRACT FROM AUTHOR]

Dietary components in early life play a role in both microbiota and intestinal immune system maturation in mammalian species. Adipokines, as endogenously produced hormones from breast milk, may have an impact on this process. The aim of the present study was to establish the influence of leptin and adiponectin supplementation during suckling on the intraepithelial lymphocyte composition, intestinal barrier function, intestinal gene expression, and gut microbiota in rat. For this purpose, newborn Wistar rats were supplemented daily with leptin, adiponectin, or whey protein concentrate during the first 21 days of life. Lymphocyte composition was established by immunofluorescence staining and flow cytometry analysis; intestinal gene expression by real-time PCR and cecal microbiota were analyzed through 16S rRNA gene sequencing. Although leptin and adiponectin were able to increase the Tc TCRαβ+ and NKT cell proportion, they decreased the NK cell percentage in IEL. Moreover, adipokine supplementation differentially modified CD8+ IEL. While the supplementation of leptin increased the proportion of CD8αα+ IEL (associated to a more intestinal phenotype), adiponectin enhanced that of CD8αβ+ (related to a peripheral phenotype). Furthermore, both adipokines enhanced the gene expression of TNF-α, MUC-2, and MUC-3, and decreased that of FcRn. In addition, the adipokine supplementations decreased the abundance of the Proteobacteria phylum and the presence of Blautia. Moreover, leptin-supplemented animals had lower relative abundance of Sutterella and a higher proportion of Clostridium genus, among others. However, supplementation with adiponectin resulted in lower abundance of the Roseburia genus and a higher proportion of the Enterococcus genus. In conclusion, the supplementation with leptin and adiponectin throughout the suckling period had an impact on both the IEL composition and the gut microbiota pattern, suggesting a modulatory role of these adipokines on the development of intestinal functionality. [ABSTRACT FROM AUTHOR]

Human milk oligosaccharides are unconjugated complex glycans present in high concentration in human milk that serve as pre-biotics and immunomodulators. They are not primarily absorbed or metabolized by the infant and reach the lower part of the intestinal tract unaltered. One of the main oligosaccharides found in human milk is 2′-fucosyllactose (2′-FL). This study aimed to investigate the effects of daily oral administration of 2′-FL in healthy suckling rats. From days 2 to 16 of life, rats were daily given the oligosaccharide (2′-FL) or vehicle (REF), weighed and their stool characteristics were assessed. On days 8 and 16 of life the morphometry, intestinal architecture, and cytokine release, mesenteric lymph nodes cell composition, plasma immunoglobulin concentrations, fecal microbiota composition, cecal short-chain fatty acids content, and the urinary metabolic profile were assessed. Animals given 2′-FL showed higher plasma IgG and IgA and more T cell subsets in the mesenteric lymph nodes on day 16. Moreover, at intestinal level, villus heights, and areas were increased on day 8. Cecal samples displayed a higher Lactobacillus proportion and a different urinary metabolic profile was observed on day 8, and a higher proportion of butyrate on day 16. In conclusion, supplementation of 2′-FL in early life has a pre-biotic and intestinal trophic effect and promotes maturation of the immune system. [ABSTRACT FROM AUTHOR]

This document is a statement of peer review for the Biology and Life Sciences Forum. The volume editors of the conference proceedings certify that all papers published in this volume have undergone peer review by expert referees. The review process was single-blind, and the conference submission management system used was Sciforum. Out of 51 submissions, 29 were accepted and 26 were published, resulting in an acceptance rate of 0.57. On average, each paper received three reviews, and a total of 100 reviewers were involved. The authors declare no conflicts of interest. [Extracted from the article]

Rotavirus (RV) is considered to be the most common cause of gastroenteritis among infants aged less than 5 years old. Human milk bioactive compounds have the ability to modulate the diarrheic process caused by several intestinal pathogens. This study aimed to evaluate the potential protective role of a specific human milk oligosaccharide, 2′-fucosyllactose (2′-FL), a mixture of the prebiotic short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides 9:1 (GOS/FOS) and their combination (2′-FL+GOS/FOS) on RV-induced diarrhea in suckling rats. The nutritional intervention was performed from the second to the sixteenth day of life by oral gavage and on day 5 an RV strain was orally administered to induce infection. Fecal samples were scored daily to assess the clinical pattern of severity, incidence and duration of diarrhea. Blood and tissues were obtained at day 8 and 16 in order to evaluate the effects on the epithelial barrier and the mucosal and systemic immune responses. In the assessment of severity, incidence and duration of diarrhea, both 2′-FL and GOS/FOS displayed a beneficial effect in terms of amelioration. However, the mechanisms involved seemed to differ: 2′-FL displayed a direct ability to promote intestinal maturation and to enhance neonatal immune responses, while GOS/FOS induced an intestinal trophic effect and an RV-blocking action. The combination of 2′-FL and GOS/FOS showed additive effects in some variables. Therefore, it could be a good strategy to add these compounds in combination to infant formulas, to protect against human RV-induced diarrhea in children. [ABSTRACT FROM AUTHOR]

At birth, when immune responses are insufficient, there begins the development of the defence capability against pathogens. Leptin and adiponectin, adipokines that are present in breast milk, have been shown to play a role in the regulation of immune responses. We report here, for the first time, the influence of in vivo adipokine supplementation on the intestinal immune system in early life. Suckling Wistar rats were daily supplemented with leptin (0·7 μg/kg per d, n 36) or adiponectin (35 μg/kg per d, n 36) during the suckling period. The lymphocyte composition, proliferation and cytokine secretion from mesenteric lymph node lymphocytes (on days 14 and 21), as well as intestinal IgA and IgM concentration (day 21), were evaluated. At day 14, leptin supplementation significantly increased the TCRαβ+ cell proportion in mesenteric lymph nodes, in particular owing to an increase in the TCRαβ+ CD8+ cell population. Moreover, the leptin or adiponectin supplementation promoted the early development CD8+ cells, with adiponectin being the only adipokine capable of enhancing the lymphoproliferative ability at the end of the suckling period. Although leptin decreased intestinal IgA concentration, it had a trophic effect on the intestine in early life. Supplementation of both adipokines modulated the cytokine profile during (day 14) and at the end (day 21) of the suckling period. These results suggest that leptin and adiponectin during suckling play a role in the development of mucosal immunity in early life. [ABSTRACT FROM AUTHOR]

Background: A 10% cocoa-enriched diet influences immune system functionality including the prevention of the antibody response and the induction of lower immunoglobulin (Ig) concentrations. However, neither cocoa polyphenols nor cocoa fiber can totally explain these immunoregulatory properties.Objectives: This study aimed to establish the influence of cocoa theobromine in systemic and intestinal Ig concentrations and to determine the effect of cocoa or theobromine feeding on lymphoid tissue lymphocyte composition.Methods: Three-week-old female Lewis rats were fed either a standard diet (AIN-93M; RF group), a 10% cocoa diet (CC group), or a 0.25% theobromine diet (the same amount provided by the cocoa diet; TB group) in 2 separate experiments that lasted 19 (experiment 1) or 8 (experiment 2) d. Serum IgG, IgM, IgA, and intestinal secretory IgA (sIgA) concentrations were determined. In addition, at the end of experiment 2, thymus, mesenteric lymph node (MLN), and spleen lymphocyte populations were analyzed.Results: Both CC and TB groups in experiments 1 and 2 showed similar serum IgG, IgM, and IgA and intestinal sIgA concentrations, which were lower than those in the RF group (46-98% lower in experiment 1 and 23-91% lower in experiment 2; P < 0.05). In addition, in experiment 2, the cocoa and theobromine diets similarly changed the thymocyte composition by increasing CD4-CD8- (+133%) and CD4+CD8- (+53%) proportions (P < 0.01), changed the MLN composition by decreasing the percentage of T-helper (Th) lymphocytes (-3%) (P = 0.015), and changed the spleen composition by increasing the proportion of Th lymphocytes (+9%) (P < 0.001) after 1 wk of diet treatment.Conclusions: The theobromine in cocoa plays an immunoregulatory role that is responsible for cocoa's influence on both systemic and intestinal antibody concentrations and also for modifying lymphoid tissue lymphocyte composition in young healthy Lewis rats. The majority of these changes are observed after a single week of being fed a diet containing 0.25% theobromine. [ABSTRACT FROM AUTHOR]

Polyphenols, widely found in edible plants, influence the immune system. Nevertheless, the immunomodulatory properties of hesperidin, the predominant flavanone in oranges, have not been deeply studied. To establish the effect of hesperidin on in vivo immune response, two different conditions of immune system stimulations in Lewis rats were applied. In the first experimental design, rats were intraperitoneally immunized with ovalbumin (OVA) plus Bordetella pertussis toxin and alum as the adjuvants, and orally given 100 or 200 mg/kg hesperidin. In the second experimental design, rats were orally sensitized with OVA together with cholera toxin and fed a diet containing 0.5% hesperidin. In the first approach, hesperidin administration changed mesenteric lymph node lymphocyte (MLNL) composition, increasing the TCRαβ+ cell percentage and decreasing that of B lymphocytes. Furthermore, hesperidin enhanced the interferon (IFN)-γ production in stimulated MLNL. In the second approach, hesperidin intake modified the lymphocyte composition in the intestinal epithelium (TCRγδ+ cells) and the lamina propria (TCRγδ+, CD45RA+, natural killer, natural killer T, TCRαβ+CD4+, and TCRαβ+CD8+ cells). Nevertheless, hesperidin did not modify the level of serum anti-OVA antibodies in either study. In conclusion, hesperidin does possess immunoregulatory properties in the intestinal immune response, but this effect is not able to influence the synthesis of specific antibodies. [ABSTRACT FROM AUTHOR]

The aim of this study was to elucidate the relationship between the urinary metabolic fingerprint and the effects of cocoa and cocoa fibre on body weight, hormone metabolism, intestinal immunity and microbiota composition. To this effect, Wistar rats were fed, for 3 weeks, a diet containing 10 % cocoa (C10) or two other diets with same the proportion of fibres: one based on cocoa fibre (CF) and another containing inulin as a reference (REF) diet. The rats’ 24 h urine samples were analysed by an untargeted 1H NMR spectroscopy-based metabonomic approach. Concentrations of faecal IgA and plasma metabolic hormones were also quantified. The C10 diet decreased the intestinal IgA, plasma glucagon-like peptide-1 and glucagon concentrations and increased ghrelin levels compared with those in the REF group. Clear differences were observed between the metabolic profiles from the C10 group and those from the CF group. Urine metabolites derived from cocoa correlated with the cocoa effects on body weight, immunity and the gut microbiota. Overall, cocoa intake alters the host and bacterial metabolism concerning energy and amino acid pathways, leading to a metabolic signature that can be used as a marker for consumption. This metabolic profile correlates with body weight, metabolic hormones, intestinal immunity and microbiota composition. [ABSTRACT FROM PUBLISHER]

Human milk contains bioactive compounds that confer a protective role against gastrointestinal infections. In order to find supplements for an infant formula able to mimic these benefits of breast-feeding, two different concepts were tested. The products consisted of the following: (1) a Bifidobacterium breve- and Streptococcus thermophilus-fermented formula and (2) a combination of short-chain galacto-oligosaccharides/long-chain fructo-oligosaccharides with pectin-derived acidic oligosaccharides. A rotavirus infection suckling rat model was used to evaluate improvements in the infectious process and in the immune response of supplemented animals. Both nutritional concepts caused amelioration of the clinical symptoms, even though this was sometimes hidden by softer stool consistency in the supplemented groups. Both products also showed certain modulation of immune response, which seemed to be enhanced earlier and was accompanied by a faster resolution of the process. The viral shedding and the in vitro blocking assay suggest that these products are able to bind the viral particles, which can result in a milder infection. In conclusion, both concepts evaluated in this study showed interesting protective properties against rotavirus infection, which deserve to be investigated further. [ABSTRACT FROM PUBLISHER]

An editorial is presented on trace mineral element concentrations under homeostatic control. Topics include analysis of Se being determined by inductively coupled plasma mass spectrometry; and Se being linked to antioxidant defense, immune function, thyroid hormone synthesis, testosterone metabolism, DNA structure, and vitamin E modulation.

An introduction is presented in which the editor discusses various reports within the issue on topics including the impact of flavonoids in inflammatory bowel disease, the mechanism and effects of quercetin in immunce function and inflammation, and the health effects of cocoa.

Previous studies have shown that a 10 % cocoa (C10) diet, containing polyphenols and fibre among others, modifies intestinal and systemic Ig production. The present study aimed at evaluating the impact of C10 on IgA and IgM production in the intestinal and extra-intestinal mucosal compartments, establishing the involvement of cocoa fibre (CF) in such effects. Mechanisms by which C10 intake may affect IgA synthesis in the salivary glands were also studied. To this effect, rats were fed either a standard diet, a diet containing C10, CF or inulin. Intestinal (the gut wash (GW), Peyer's patches (PP) and mesenteric lymph nodes (MLN)) and extra-intestinal (salivary glands) mucosal tissues and blood samples were collected for IgA and IgM quantification. The gene expressions of IgA production- and homing-related molecules were studied in the salivary glands. The C10 diet decreased intestinal IgA and IgM production. Although the CF diet decreased the GW IgA concentration, it increased PP, MLN and serum IgA concentrations. Both the C10 and the CF diets produced a down-regulatory effect on IgA secretion in the extra-intestinal tissues. The C10 diet interacted with the mechanisms involved in IgA synthesis, whereas the CF showed particular effects on the homing and transcytosis of IgA across the salivary glands. Overall, CF was able to up-regulate IgA production in the intestinal-inductor compartments, whereas it down-regulated its production at the mucosal-effector ones. Further studies must be directed to ascertain the mechanisms involved in the effect of particular cocoa components on gut-associated lymphoid tissue. [ABSTRACT FROM AUTHOR]

Cocoa powder, a rich source of polyphenols, has shown immunomodulatory properties in both the intestinal and systemic immune compartments of rats. The aim of the current study was to establish the effect of a cocoa diet in a rat oral sensitization model and also to gain insight into the mesenteric lymph nodes (MLN) activities induced by this diet. To achieve this, three-week-old Lewis rats were fed either a standard diet or a diet with 10% cocoa and were orally sensitized with ovalbumin (OVA) and with cholera toxin as a mucosal adjuvant. Specific antibodies were quantified, and lymphocyte composition, gene expression, and cytokine release were established in MLN. The development of anti-OVA antibodies was almost totally prevented in cocoa-fed rats. In addition, this diet increased the proportion of TCRγδ+ and CD103+CD8+ cells and decreased the proportion of CD62L+CD4+ and CD62L+CD8+ cells in MLN, whereas it upregulated the gene expression of OX40L, CD11c, and IL-1β and downregulated the gene expression of IL-17α. In conclusion, the cocoa diet induced tolerance in an oral sensitization model accompanied by changes in MLN that could contribute to this effect, suggesting its potential implication in the prevention of food allergies. [ABSTRACT FROM AUTHOR]

The article offers information on the Second International Congress on Chocolate and Cocoa in Medicine organized by the International Society of Chocolate and Cocoa in Medicine (ISCHOM) held in Barcelona, Spain from September 25-26, 2015.

Background: Food allergy (FA) is an adverse health effect produced by the exposure to a given food. Currently, there is no optimal animal model of FA for the screening of immunotherapies or for testing the allergenicity of new foods. Objective: The aim of the present study was to develop an effective and rapid model of FA in Brown Norway rats. In order to establish biomarkers of FA in rat, we compared the immune response and the anaphylactic shock obtained in this model with those achieved with only intraperitoneal immunization. Methods: Rats received an intraperitoneal injection of ovalbumin (OVA) with alum and toxin from Bordetella pertussis, and 14 days later, OVA by oral route daily for three weeks (FA group). A group of rats receiving only the i.p. injection (IP group) were also tested. Serum anti-OVA IgE, IgG1, IgG2a, IgG2b and IgA antibodies were quantified throughout the study. After an oral challenge, body temperature, intestinal permeability, motor activity, and mast cell protease II (RMCP-II) levels were determined. At the end of the study, anti-OVA intestinal IgA, spleen cytokine production, lymphocyte composition of Peyer’s patches and mesenteric lymph nodes, and gene expression in the small intestine were quantified. Results: Serum OVA-specific IgG1, IgG2a and IgG2b concentrations rose with the i.p. immunization but were highly augmented after the oral OVA administration. Anti-OVA IgE increased twofold during the first week of oral OVA gavage. The anaphylaxis in both IP and FA groups decreased body temperature and motor activity, whereas intestinal permeability increased. Interestingly, the FA group showed a much higher RMCP II serum protein and intestinal mRNA expression. Conclusions: These results show both an effective and relatively rapid model of FA assessed by means of specific antibody titres and the high production of RMCP-II and its intestinal gene expression. [ABSTRACT FROM AUTHOR]

A diet containing 10 % cocoa, a rich source of polyphenols and fibre, is able to modify intestinal immune status as well as microbiota composition. The present study was aimed at investigating whether cocoa flavonoid content is uniquely responsible for these modulatory effects of cocoa, and to establish whether these effects depend on the rat strain. To this end, 3-week-old Wistar and Brown Norway rats were fed, for 4 weeks, either a standard diet or the following three isoenergetic diets containing increasing proportions of cocoa flavonoids from different sources: one with 0·2 % polyphenols (from conventional defatted cocoa), and two others with 0·4 and 0·8 % polyphenols (from non-fermented cocoa, very rich in polyphenols). Serum Ig concentrations, faecal IgA levels, microbiota composition and IgA-coating bacterial proportion were evaluated at the beginning and at the end of the study. After the nutritional intervention, the composition of lymphocytes in Peyer's patches and mesenteric lymph nodes was evaluated. In some respects, the Wistar strain was more sensitive to the impact of the cocoa diets than the Brown Norway strain. After 4 weeks of dietary intervention, similar modulatory effects of the diets containing 0·2 and 0·8 % polyphenols on mucosal IgA levels and microbiota composition were found, although the 0·2 % diet, with a higher proportion of theobromine and fibre, had more impact, suggesting that polyphenols are not the only components involved in such effects. [ABSTRACT FROM PUBLISHER]

Fish oil supplementation during pregnancy alters breast milk composition, but there is little information about the impact of oily fish consumption. We determined whether increased salmon consumption during pregnancy alters breast milk fatty acid composition and immune factors. Women (n = 123) who rarely ate oily fish were randomly assigned to consume their habitual diet or to consume 2 portions of farmed salmon per week from 20 wk of pregnancy until delivery. The salmon provided 3.45 g long-chain (LC) (n-3) PUFA/wk. Breast milk fatty acid composition and immune factors [soluble CD14, transforming growth factor-&bgr; (TGF&bgr;)1, TGF&bgr;2, and secretory IgA] were analyzed at 1, 5, 14, and 28 d postpartum (PP). Breast milk from the salmon group had higher proportions of EPA (80%), docosapentaenoic acid (30%), and DHA (90%) on d 5 PP compared with controls (P < 0.01 ), The LC (n-6) PUFA:LC (n-3) PUFA ratio was lower for the salmon group on all days of PP sampling (P ≤ 0.004), although individual (n-6) PUFA proportions, including arachidonic acid, did not differ. All breast milk immune factors decreased between d 1 and 28 PP (P< 0.001). Breast milk secretory IgA (sIgA) was lower in the salmon group (d 1-28 PP; P= 0.006). Salmon consumption during pregnancy, at the current recommended intakes, increases the LC (n-3) PUFA concentration of breast milk in early lactation, thus improving the supply of these important fatty acids to the breast-fed neonate. The consequence of the lower breast milk concentration of sIgA in the salmon group is not clear. J [ABSTRACT FROM AUTHOR]

Previously we established that a cocoa-enriched diet in young rats reduces specific antibody production and the T helper (Th) lymphocyte proportion in lymphoid tissues. The aim of the present study was to ascertain the modulatory ability of a cocoa flavonoid-enriched diet on collagen-induced arthritis (CIA), which is mediated by anti-collagen autoantibody response and Th lymphocyte activation. Female Louvain (LOU) rats were fed with a cocoa-enriched diet, beginning 2 weeks before CIA induction. Hind-paw swelling and serum cytokine and anti-collagen antibody concentrations were determined. Anti-collagen antibody-secreting cell counts and lymphocyte subset proportions were established in inguinal lymph nodes (ILN). Reactive oxygen species (ROS), nitric oxide (NO) and TNFα produced by peritoneal macrophages were determined. Although arthritic cocoa-fed rats showed a similar hind-paw swelling time course as the arthritic animals fed a standard diet, the cocoa intake was able to decrease specific IgG2a, IgG2b and IgG2c titres. Moreover, cocoa intake in CIA rats reduced ROS production, TNFα and NO release from peritoneal macrophages, and decreased the Th:cytotoxic T cell ratio in ILN. In conclusion, a cocoa flavonoid-enriched diet in LOU rats with CIA produced no effect on hind-paw swelling but was able to modulate the specific antibody response and also the Th lymphocyte proportion, as well as the synthesis of pro-inflammatory mediators from peritoneal macrophages. Therefore, a cocoa-enriched diet could be a good adjuvant therapy in disorders with oxidative stress or autoimmune pathogenesis. [ABSTRACT FROM PUBLISHER]

Cocoa and its flavonoids have potential anti-inflammatory properties in vitro and in acute inflammation models in vivo. The aim of the present study was to ascertain the effects of two cocoa-enriched diets on adjuvant arthritis (AA) in rats, considering not only clinical and biochemical inflammatory indices, but also antibody response and lymphocyte composition. Female Wistar rats were fed with a 5 or 10 % cocoa-enriched diet beginning 2 weeks before arthritis induction and until the end of the study. AA was induced by an intradermal injection of heat-killed Mycobacterium butyricum suspension. The hind-paw swelling (plethysmometry), serum anti-mycobacterial antibody concentration (ELISA), blood and inguinal lymph node lymphocyte subset percentage (flow cytometry), and IL-2, interferon γ and PGE2 released from splenocytes (ELISA) were assessed. Although the cocoa diets had no significant effect on hind-paw swelling, a tendency to reduce it was observed at the end of the study. Cocoa-enriched diets were able to decrease the serum anti-mycobacterial antibody concentration and the splenocyte PGE2 production, as well as the proportion of T-helper (Th) lymphocytes in blood and regional lymph nodes, which probably includes cells responsible for the arthritic process. The cocoa diets prevented a decrease in the proportion of regulatory T-cells in blood and a disequilibrium between inguinal lymph node natural killer (NK) CD8+ and NK CD8− subsets. In conclusion, the cocoa-enriched diets during AA were not able to significantly decrease joint inflammation but modified Th-cell proportions and prevented specific antibody synthesis. [ABSTRACT FROM PUBLISHER]

Diet plays a crucial role in maintaining optimal immune function. Research demonstrates the immunomodulatory properties and mechanisms of particular nutrients; however, these aspects are studied less in early life, when diet may exert an important role in the immune development of the neonate. Besides the limited data from epidemiological and human interventional trials in early life, animal models hold the key to increase the current knowledge about this interaction in this particular period. This paper reports the potential of the suckling rat as a model for immunonutrition studies in early life. In particular, it describes the main changes in the systemic and mucosal immune system development during rat suckling and allows some of these elements to be established as target biomarkers for studying the influence of particular nutrients. Different approaches to evaluate these immune effects, including the manipulation of the maternal diet during gestation and/or lactation or feeding the nutrient directly to the pups, are also described in detail. In summary, this paper provides investigators with useful tools for better designing experimental approaches focused on nutrition in early life for programming and immune development by using the suckling rat as a model. [ABSTRACT FROM AUTHOR]

Human breast milk is the ideal nutrition for the newborn, and in addition to its nutritional contribution, necessary for infant growth and development, it contains various immune bioactive factors that confer so~e of the numerous beneficial effects of breastfeeding. The current study analyzed the concentrations of IgA, growth factors such as epidermal growth factor (EGF), TGFβ1,and TGFβ2, cytokines IL-6, IL-8, IL-b, IL-13, and TNFα, and TNF-receptor I (TNF-RI) in colostrum and transitional and mature milk from mothers with mature, premature, and very premature infants. Human milk samples were collected from mothers delivering at term ITI, preterm IPTI, and very preterm (VPT). Milk from all the mothers was collected at 3 different time points after delivery corresponding to colostrum and transitional and mature milk. After obtaining milk whey, IgA, EGF, TGFβ1, and TGFβ2 were determined by ELISA and I L-6, IL-8, IL-10, IL-23, TNFα and TNF-RI by cytometric bead array immunoassay. The colostrum of the PT group was extremely rich-in most of the factors studied, but higher concentrations than in the T group were only found for IL-6 (P = 0.0511, TGFI31, and TGF/32 IP < 0.051. Conversely, the colostrum of the VPT group had lower concentrations of IgA, IL-8, IL-10, and TNFα than those in the T group (P < 0.05). Results suggest that maternal lactogenic compensatory mechanisms accelerating the development of immature breast-fed preterm infants may take effect only after wk 30 of gestation. [ABSTRACT FROM AUTHOR]