Search

Peptides from several plant food proteins not only maintain the nutritional values of the original protein and decrease the environmental impact of animal agriculture, but also exert biological activities with significant health-beneficial effects. Wheat is the most important food grain source in the world. However, negative attention on wheat-based products has arose due to the role of gluten in celiac disease. A controlled enzymatic hydrolysis could reduce the antigenicity of wheat gluten protein hydrolysates (WGPHs). Therefore, the aims of the present study were to evaluate the effects of the in vitro administration of Alcalase-generated WGPHs on the immunological and antioxidant responses of human peripheral blood mononuclear cells (PBMCs) from 39 healthy subjects. WGPH treatment reduced cell proliferation and the production of the Type 1 T helper (Th1) and Th17 pro-inflammatory cytokines IFN-γ and IL-17, respectively. WPGHs also improved the cellular anti-inflammatory microenvironment, increasing Th2/Th1 and Th2/Th17 balances. Additionally, WGPHs improved global antioxidant capacity, increased levels of the reduced form of glutathione and reduced nitric oxide production. These findings, not previously reported, highlight the beneficial capacity of these vegetable protein hydrolysates, which might represent an effective alternative in functional food generation., This work was supported by the Spanish Government, Ministerio de Economía y Competitividad (AGL2012-40247-C02-01 and AGL2012-40247-C02-02) the Andalusian Government Ministry of Health (PC-0111-2016-0111) and the PAIDI Program from the Andalusian Government (CTS160). I.C.-C. was supported by Ministerio de Economía y Competitividad (AGL2012-40247-C02-02) and by a FPU grant from the Spanish Ministerio de Educación, Cultura y Deporte (FPU13/01210). N.Á.-S. was supported by Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (RD06/0013/0001 and RD12/0043/0012). G.S.-S. was supported by a FPU grant from the Spanish Ministerio de Educación, Cultura y Deporte (FPU16/02339). I.B. was supported by the VI Program of Inner Initiative for Research and Transfer of University of Seville (VI PPIT-US).

The study evaluated the symptoms, acceptance, and digestibility of bread made from transgenic low-gliadin wheat, in comparison with gluten free bread, in Non-coeliac gluten sensitivity (NCGS) patients, considering clinical/sensory parameters and gut microbiota composition. This study was performed in two phases of seven days each, comprising a basal phase with gluten free bread and an E82 phase with low-gliadin bread. Gastrointestinal clinical symptoms were evaluated using the Gastrointestinal Symptom Rating Scale (GSRS) questionnaire, and stool samples were collected for gluten immunogenic peptides (GIP) determination and the extraction of gut microbial DNA. For the basal and E82 phases, seven and five patients, respectively, showed undetectable GIPs content. The bacterial 16S rRNA gene V1-V2 hypervariable regions were sequenced using the Illumina MiSeq platform and downstream analysis was done using a Quantitative Insights into Microbial Ecology (QIIME) pipeline. No significant differences in the GSRS questionnaires were observed between the two phases. However, we observed a significantly lower abundance of some gut genera Oscillospira, Dorea, Blautia, Bacteroides, Coprococcus, and Collinsella, and a significantly higher abundance of Roseburia and Faecalibacterium genera during the E82 phase compared with the basal phase. The consumption of low-gliadin bread E82 by NCGS subjects induced potentially positive changes in the gut microbiota composition, increasing the butyrate-producing bacteria and favoring a microbial profile that is suggested to have a key role in the maintenance or improvement of gut permeability., The Spanish Ministry of Economy and Competitiveness (Projects AGL2013-48946-C3-1-R, AGL2013-48946-C and AGL2016-80566-P) and the European Regional Development Fund (FEDER) supported this research.

Meat and meat products have been described as a very good source of angiotensin I converting enzyme (ACEI)-inhibitory peptides. The generation of bioactive peptides can occur through the action of endogenous muscular enzymes during processing, gastrointestinal digestion, or by using commercial enzymes in laboratory or industry under controlled conditions. Studies of bioavailability are necessary in order to prove the positive health effect of bioactive peptides in the body as they should resist gastrointestinal digestion, cross the intestinal barrier, and reach blood stream and target organs. However, in order to better understand their effect, interactions, and bioavailability, it is necessary to consider food matrix interactions and continue the development of quantitative methodologies in order to obtain more data that will enable advances in the field of bioactive peptides and the determination of their influence on health., This research was funded by grant AGL2017-89381-R and FEDER funds from the Spanish Ministry of Science, Innovation, and Universities. Ramón y Cajal postdoctoral contract to L.M. is also acknowledged.

Previous studies have shown that a resistant dextrin soluble fibre has prebiotic properties with related health benefits on blood glucose management and satiety. Our aim was to demonstrate the effects of continuous administration of resistant dextrin on intestinal gas production, digestive sensations, and gut microbiota metabolism and composition. Healthy subjects (n = 20) were given resistant dextrin (14 g/d NUTRIOSE®, Roquette Frères, Lestrem, France) for four weeks. Outcomes were measured before, at the beginning, end, and two weeks after administration: anal evacuations of gas during daytime; digestive perception, girth, and gas production in response to a standard meal; sensory and digestive responses to a comfort meal; volume of colonic biomass by magnetic resonance; taxonomy and metabolic functions of fecal microbiota by shotgun sequencing; metabolomics in urine. Dextrin administration produced an initial increase in intestinal gas production and gas-related sensations, followed by a subsequent decrease, which magnified after discontinuation. Dextrin enlarged the volume of colonic biomass, inducing changes in microbial metabolism and composition with an increase in short chain fatty acids-producing species and modulation of bile acids and biotin metabolism. These data indicate that consumption of a soluble fibre induces an adaptative response of gut microbiota towards fermentative pathways with lower gas production., This work was supported by a grant from Roquette. The research activities were supported in part by the projects PID2021-122295OB-I00 (Ministerio de Ciencia e Innovación, Spain), PID2019-103914RB-I00 (Ministerio de Ciencia e Innovación, Spain), AGL2016-78311-R (Ministerio de Ciencia e Innovación, Spain) and FJC2019-042125-I (Ministerio de Ciencia e Innovación, Spain). Ciberehd is funded by the Instituto de Salud Carlos III.

Obesity has reached pandemic proportions and has become a major health concern worldwide. Therefore, it is necessary to find new strategies against this condition and its associated comorbidities. Green coffee polyphenols (GCP) and oat beta-glucans (BGs) have proven their hypolipidaemic and hypoglycaemic effects. This study aimed to examine the effects of the long-term consumption of supplements containing GCP, BG or the novel GCP/BG combination on lipid and glucose metabolism biomarkers in overweight/obese subjects who maintained their dietary habits and physical activity, hence addressing the difficulty that this population faces in adapting to lifestyle changes. A randomised, crossover, blind trial was carried out in 29 volunteers who consumed either GCP (300 mg), BG (2.5 g) or GCP/BG (300 mg + 2.5 g) twice a day for 8 weeks. Blood samples were collected, and blood pressure and body composition were measured at the beginning and end of each intervention. Total cholesterol, triglycerides, high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), very low-density lipoprotein (VLDL-C) cholesterol, glycated haemoglobin, fasting glucose, insulin, aspartate transaminase, alanine transaminase and different hormones and adipokines were analysed. Only VLDL-C (p = 0.01) and diastolic blood pressure (p = 0.027) decreased after the intervention, especially with the BG supplement. There were no other significant changes in the analysed biomarkers. In conclusion, the regular intake of GCP, BG and GCP/BG without lifestyle changes is not an efficient strategy to improve lipid and glucose homeostasis in overweight/obese subjects., This research was funded by project AGL2015-69986-R from the Spanish Ministry of Economy and Competitivity. J.G.-C. had a predoctoral grant funded by Comunidad de Madrid (PEJD-2017-PRE_BIO-4225). M.A.S. had a predoctoral contract funded by Comunidad de Madrid (PEJD-2018-PRE/SAL-9104). S.G.-R. had a predoctoral contract funded by Interprofesional del Aceite de Orujo de Oliva (ORIVA).

Major susceptibility to alterations in liver function (e.g., hepatic steatosis) in a prone environment due to circadian misalignments represents a common consequence of recent sociobiological behavior (i.e., food excess and sleep deprivation). Natural compounds and, more concisely, polyphenols have been shown as an interesting tool for fighting against metabolic syndrome and related consequences. Furthermore, mitochondria have been identified as an important target for mediation of the health effects of these compounds. Additionally, mitochondrial function and dynamics are strongly regulated in a circadian way. Thus, we wondered whether some of the beneficial effects of grape-seed procyanidin extract (GSPE) on metabolic syndrome could be mediated by a circadian modulation of mitochondrial homeostasis. For this purpose, rats were subjected to “standard”, “cafeteria” and “cafeteria diet + GSPE” treatments (n = 4/group) for 9 weeks (the last 4 weeks, GSPE/vehicle) of treatment, administering the extract/vehicle at diurnal or nocturnal times (ZT0 or ZT12). For circadian assessment, one hour after turning the light on (ZT1), animals were sacrificed every 6 h (ZT1, ZT7, ZT13 and ZT19). Interestingly, GSPE was able to restore the rhythm on clock hepatic genes (Bmal1, Per2, Cry1, Rorα), as this correction was more evident in nocturnal treatment. Additionally, during nocturnal treatment, an increase in hepatic fusion genes and a decrease in fission genes were observed. Regarding mitochondrial complex activity, there was a strong effect of cafeteria diet at nearly all ZTs, and GSPE was able to restore activity at discrete ZTs, mainly in the diurnal treatment (ZT0). Furthermore, a differential behavior was observed in tricarboxylic acid (TCA) metabolites between GSPE diurnal and nocturnal administration times. Therefore, GSPE may serve as a nutritional preventive strategy in the recovery of hepatic-related metabolic disease by modulating mitochondrial dynamics, which is concomitant to the restoration of the hepatic circadian machinery. España Ministry of Economy and Competitiveness (MINECO), AGL2016-77105-R (CHRONOFOOD project).

Nutritional status during gestation can influence mother and offspring metabolism. Undernutrition in pregnancy affects women in both western and developing countries, and it is associated with a high prevalence of chronic diseases in later life. The present work was conducted in the rabbit model, as a longitudinal study, to examine the effect of food restriction during early and mid-gestation, and re-feeding ad libitum until the end of pregnancy on metabolic status and body reserves of mother and, its association with development and metabolism of fetuses and female offspring to the juvenile stage. Little changes in live body weight (LBW), compensatory feed intake, similar body reserves, and metabolism were observed in dams. Placenta biometry and efficiency were slightly affected, but fetal BW and phenotype were not modified. However, hyperinsulinemia, insulin resistance, and hypertriglyceridemia were demonstrated in pre-term fetuses. In the juvenile period, these changes were not evidenced, and a similar pattern of growth and serum metabolic parameters in offspring of food-restricted mothers were found, except in serum aminotransferases levels, which increased. These were associated with higher liver fibrosis. Maternal food restriction in the early and mid-pregnancy followed by re-feeding in our rabbit model established a compensatory energy status in dams and alleviated potential long-term consequences in growth and metabolism in the offspring, even if fetal metabolism was altered., This research was funded by the SPANISH MINISTRY OF SCIENCE (Grant Number: AGL2015-65572-C2-1-R and -2-R, RTI-2018-094404-B-C21 and C22) and UCM funding for RESEARCH GROUPS (Group 920249).

This article belongs to the Special Issue Dietary Biomarkers in Human Nutrition., There are some studies that suggest that moderate consumption of wine, as part of a healthy and balanced diet, has a favourable effect on intestinal health. This study evaluates the effect of moderate wine consumption on faecal water (FW) cytotoxicity as a parameter of gut health. To that end, faecal samples before and after a red wine intervention study (250 mL of wine/day, 4 weeks) in healthy volunteers (n = 8) and in a parallel control group (n = 3) were collected and assayed for in vitro FW cytotoxicity. Two reference compounds, phenol and p-cresol, were used for assessing the cytotoxicity assays using two colon epithelial cell lines (HT-29 and HCT 116) and different assay conditions (FW dilution and incubation time). For the two cell lines and all assay conditions, the means of percentage cell viability were higher (lower cytotoxicity) for samples collected after the red wine intervention than for those collected before, although significant (p < 0.05) differences were only found in certain assay conditions for both cell lines. Significant positive correlations between the percentage cell viability and the contents of some faecal metabolites (short-chain fatty acids (SCFA) and phenolic acids (PA)) were found for the more resistant cell line (HCT 116), suggesting that the reduction in FW cytotoxicity observed after moderate red wine consumption was related to the production of microbial-derived metabolites such as SCFA and PA, whose faecal contents have been shown to increase after wine consumption. FW cytotoxicity can be deemed as a holistic biomarker that involves diet, gut microbiota and host., Research in our lab is funded by Grants AGL2015-64522-C2-R (Spanish Ministry of Science and Innovation) and ALIBIRD-CM 2020 P2018/BAA-4343 (Comunidad de Madrid).

Today, cardiovascular disease has a great impact on the global population due to its high prevalence. One challenge that cardiovascular patients face to achieve a better prognosis is to follow a healthy diet. This study focused on psychological factors linked to adaptation to a healthy diet in these patients. The main objective was to analyze the interrelationship between motivation to follow a healthy diet and self-efficacy to adhere to the Mediterranean diet with life satisfaction over time. The sample consisted of cardiovascular patients who were assessed at three measurement moments (NT1 = 755, NT2 = 593, NT3 = 323, average interval time: nine months). Correlation analyses showed that self-efficacy, motivation, and life satisfaction followed a pattern of positive relations across the three measurements. A time effect over the study variables was also observed. The results of path analyses showed that self-efficacy positively predicted autonomous motivation, which in turn was associated with patients&rsquo, life satisfaction. This interrelation was stable over a period of 18 months. Moreover, life satisfaction predicted self-efficacy nine months later. Psychological interventions might be a positive resource for cardiovascular patients, since psychological variables influence their life satisfaction and their subsequent quality of life in their new health condition.

There is limited evidence of phenolic compounds acting as protective agents on several cancer types, including breast cancer (BC). Nevertheless, some polyphenol classes have not been investigated and there is a lack of studies assessing the effect on menopausal status and hormone receptor status as influenced by these compounds. The objective of this study is to evaluate the association between the intake of all polyphenol classes in relation to the BC risk by menopausal and hormone receptor status. We used data from a population-based multi-case-control study (MCC-Spain) including 1472 BC cases and 1577 controls from 12 different regions of Spain. The odds ratios (ORs) with 95% CI were calculated using logistic regression of mixed effects by quartiles and log2 of polyphenol intakes (adjusted for the residual method) of overall BC, menopausal and receptor status. No associations were found between total intake of polyphenols and BC risk. However, inverse associations were found between stilbenes and all BC risk (ORQ4 vs. Q1: 0.70, 95%CI: 0.56&ndash, 0.89, Ptrend = 0.001), the consumption of hydroxybenzaldehydes (ORQ4 vs. Q1: 0.75, 95%CI: 0.59&ndash, 0.93, Ptrend = 0.012) and hydroxycoumarins (ORQ4 vs. Q1: 0.73, 95%CI: 0.57&ndash, 0.93, Ptrend = 0.005) were also inversely associated. The intake of stilbenes, hydroxybenzaldehydes and hydroxycoumarins can contribute to BC reduction risk on all menopausal and receptor statuses.

The improvement of the nutritional quality of dairy foods has become a key strategy for reducing the risk of developing diet-related non-communicable diseases. In this context, we aimed to optimize the concentration of inulin in combination with 10 mg/mL of coffee-cascara extract in yogurt while considering their effect on appetite control, gastrointestinal wellbeing, and their effect on the sensory and technological properties of the product. For this purpose, we tested four coffee-cascara yogurt treatments in a blind cross-over nutritional trial with 45 healthy adults: a coffee-cascara yogurt without inulin (Y0) and coffee-cascara yogurts containing 3% (Y3), 7% (Y7), and 13% (Y13) of inulin. The ratings on sensory acceptance, satiety, gastrointestinal tolerance, and stool frequency were measured. Surveys were carried out digitally in each participant&rsquo, s cellphone. Yogurt pH, titratable acidity, syneresis, and instrumental texture were analyzed. Inulin addition increased the yogurt&rsquo, s firmness and consistency. Y13 achieved significantly higher overall acceptance, texture, and taste scores than Y0 (p &lt, 0.05). Y3 presented similar gastrointestinal tolerance to Y0. However, 7% and 13% of inulin produced significant (p &lt, 0.05) bloating and flatulence when compared to Y0. The appetite ratings were not significantly affected by the acute intake of the different yogurts. Overall, Y3 was identified as the formulation that maximized nutritional wellbeing, reaching a &ldquo, source of fiber&rdquo, nutritional claim, without compromising its technological and sensory properties.

The low molecular weight peptide composition of virgin olive oil (VOO) is mostly unknown. We hypothesised that unfiltered VOO could possess low molecular weight peptides with antihypertensive activity. We produced unfiltered VOO and obtained a water-soluble peptide extract from it. The peptides were separated by size-exclusion using fast protein liquid chromatography, and the low molecular weight fraction was analysed by nanoscale liquid chromatography-Orbitrap coupled with tandem mass spectrometry and de novo sequencing. We selected 23 peptide sequences containing between 6 and 9 amino acids and molecular masses ranging 698&ndash, 1017 Da. Those peptides were chemically synthesised and their angiotensin-converting enzyme (ACE) inhibitory activity was studied in vitro. Seven peptides showed a strong activity, with half maximal inhibitory concentration (IC50) &lt, 10 &micro, m. The antihypertensive effects of the four most active synthesised ACE inhibitor peptides were studied in spontaneously hypertensive rats (SHR). Acute oral administration of synthetic peptides RDGGYCC and CCGNAVPQ showed antihypertensive activity in SHR. We conclude that unfiltered VOO naturally contains low molecular weight peptides with specific ACE inhibitory activity and antihypertensive effects in SHR.

Wheat gluten proteins are responsible for the bread-making properties of the dough but also for triggering important gastrointestinal disorders. Celiac disease (CD) affects approximately 1% of the population in Western countries. The only treatment available is the strict avoidance of gluten in the diet. Interference RNA (RNAi) is an excellent approach for the down-regulation of genes coding for immunogenic proteins related to celiac disease, providing an alternative for the development of cereals suitable for CD patients. In the present work, we report a comparative study of the stimulatory capacity of seven low-gluten RNAi lines differing in grain gluten and non-gluten protein composition, relevant for CD and other gluten pathologies. Peripheral blood mononuclear cells (PBMCs) of 35 patients with active CD were included in this study to assess the stimulatory response induced by protein extracts from the RNAi lines. Analysis of the proliferative response and interferon-gamma (INF-&gamma, ) release of PBMCs demonstrated impaired stimulation in response to all RNAi lines. The lower response was provided by lines with a very low content of &alpha, and &gamma, gliadins, and low or almost devoid of DQ2.5 and p31&ndash, 43 &alpha, gliadin epitopes. The non-gluten protein seems not to play a key role in PBMC stimulation.

This study aimed to complete the scientific basis for the validation of a coffee silverskin extract (CSE) as a novel food ingredient according to European legislation. Nutritional value, safety, effects on biochemical biomarkers and excretion of short chain fatty acids (SCFAs) in vivo of CSE were assessed. Proteins, amino acids, fat, fatty acids, fiber, simple sugars and micronutrients were analyzed. For the first time, toxicological and physiological effects were evaluated in vivo by a repeated-dose study in healthy Wistar rats. Hormone secretion, antioxidant (enzymatic and no-enzymatic) and anti-inflammatory biomarkers, and dietary fiber fermentability of CSE (analysis of SCFAs in feces) were studied in biological samples. This unique research confirms the feasibility of CSE as a human dietary supplement with several nutrition claims: &ldquo, source of proteins (16%), potassium, magnesium, calcium and vitamin C, low in fat (0.44%) and high in fiber (22%)&rdquo, This is the first report demonstrating that its oral administration (1 g/kg) for 28 days is innocuous. Hormone secretion, antioxidant or anti-inflammatory biomarkers were not affected in heathy animals. Total SCFAs derived from CSE fiber fermentation were significantly higher (p &lt, 0.05) in male treated rats compared to male control rats. All the new information pinpoints CSE as a natural, sustainable and safe food ingredient containing fermentable fiber able to produce SCFAs with beneficial effects on gut microbiota.

The prevalence of renal and cardiovascular disease (CVD) in patients with systemic lupus erythematosus (SLE) is higher than in general populations. Recently, a causal role of gut microbiota on the development of immune responses in SLE has been described. Probiotic consumption changes the composition of gut microbiota, preventing SLE progression. The aim of this review is to explore the role of the gut microbiota in the development of renal and cardiovascular disease in SLE and how probiotics could be a therapeutic option. Despite strong evidence on the beneficial effects of probiotics in the development of autoimmunity and nephritis in SLE, only a few studies described the protective effects of Lactobacillus in important risk factors for CVD, such as endothelial dysfunction and hypertension in mice. The preventive effects of probiotics in renal and CVD in humans have not been established yet., This work was supported by grants from Comisión Interministerial de Ciencia y Tecnología, Ministerio de Economía y competitividad (MINECO) (SAF2014-55523-R, SAF2017-84894-R) and Junta de Andalucía (Proyecto de excelencia P12-CTS-2722, and CTS 164), with funds from the European Union, and by the Ministerio de Economia y Competitividad, Instituto de Salud Carlos III (CIBER-CV). I.R.-V. is a predoctoral fellow of MINECO; N.d.l.V. is a predoctoral fellow of Junta de Andalucía and Fondo Social Europeo “FEDER una manera de hacer Europa”, and M.T. is a postdoctoral fellow of Instituto de Salud Carlos III (Sara Borrell Program).

Walnuts are rich in polyphenols ellagitannins, modulate gut microbiota (GM), and exert health benefits after long-term consumption. The metabolism of ellagitannins to urolithins via GM depends on urolithin metabotypes (UM-A, -B, or -0), which have been reported to predict host responsiveness to a polyphenol-rich intervention. This study aims to assess whether UMs were associated with differential GM modulation after short-term walnut consumption. In this study, 27 healthy individuals consumed 33 g of peeled raw walnuts over three days. GM profiling was determined using 16S rRNA illumina sequencing and specific real-time quantitative polymerase chain reactions (qPCRs), as well as microbial activity using short-chain fatty acids analysis in stool samples. UMs stratification of volunteers was assessed using ultra performance liquid chromatography&ndash, electro spray ionization&ndash, quadrupole time of flight&ndash, mass spectrometry (UPLC-ESI-QTOF-MS) analysis of urolithins in urine samples. The gut microbiota associated with UM-B was more sensitive to the walnut intervention. Blautia, Bifidobacterium, and members of the Coriobacteriaceae family, including Gordonibacter, increased exclusively in UM-B subjects, while some members of the Lachnospiraceae family decreased in UM-A individuals. Coprococcus and Collinsella increased in both UMs and higher acetate and propionate production resulted after walnuts intake. Our results show that walnuts consumption after only three days modulates GM in a urolithin metabotype-depending manner and increases the production of short-chain fatty acids (SCFA).

Bioactive supplements display relevant therapeutic properties when properly applied according to validated molecular effects. Our previous research efforts established the basis to develop a dietary supplement based on a Rosmarinus officinalis supercritical extract. This was enriched in phenolic diterpenes (RE) with proven properties against signaling pathways involved in colon tumorigenesis, and shark liver oil rich in alkylglycerols (AKG) as a bioactive lipid vehicle to improve RE bioavailability and synergize with the potential therapeutic action of the extract. Herein, we have investigated the tolerability and safety of the supplement and the biological and molecular effects from an immuno-nutritional perspective. Sixty healthy volunteers participated in a six week, double-blind, randomized parallel pilot study with two study arms: RE-AKG capsules (CR) and control capsules (CC). Mean age (&plusmn, SD) of volunteers was 28.32 (&plusmn, 11.39) and 27.5 (&plusmn, 9.04) for the control and the study groups, respectively. Safety of the CR product consumption was confirmed by analyzing liver profile, vital constants, and oxidation markers (LDLox in blood and isoprostanes and thromboxanes in urine). The following were monitored: (1) the phenotyping of plasmatic leukocytes and the ex vivo response of lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs), (2) expression of genes associated with immune-modulation, inflammation, oxidative stress, lipid metabolism, and tumorigenesis, and (3) the correlation of selected genetic variants (SNPs) with the differential responses among individuals. The lack of adverse effects on liver profile and oxidation markers, together with adequate tolerability and safe immunological adaptations, provide high-quality information for the potential use of CR as co-adjuvant of therapeutic strategies against colorectal cancer.

The consumption of antioxidant-rich foods such as virgin olive oil (VOO) promotes high-density lipoprotein (HDL) anti-atherogenic capacities. Intake of functional VOOs (enriched with olive/thyme phenolic compounds (PCs)) also improves HDL functions, but the gene expression changes behind these benefits are not fully understood. Our aim was to determine whether these functional VOOs could enhance the expression of cholesterol efflux-related genes. In a randomized, double-blind, crossover, controlled trial, 22 hypercholesterolemic subjects ingested for three weeks 25 mL/day of: (1) a functional VOO enriched with olive oil PCs (500 mg/kg), (2) a functional VOO enriched with olive oil (250 mg/kg) and thyme PCs (250 mg/kg, FVOOT), and, (3) a natural VOO (olive oil PCs: 80 mg/kg, control intervention). We assessed whether these interventions improved the expression of cholesterol efflux-related genes in peripheral blood mononuclear cells by quantitative reverse-transcription polymerase chain reactions. The FVOOT intervention upregulated the expression of CYP27A1 (P = 0.041 and P = 0.053, versus baseline and the control intervention, respectively), CAV1 (P = 0.070, versus the control intervention), and LXR&beta, RXR&alpha, and PPAR&beta, /&delta, (P = 0.005, P = 0.005, and P = 0.038, respectively, relative to the baseline). The consumption of a functional VOO enriched with olive oil and thyme PCs enhanced the expression of key cholesterol efflux regulators, such as CYP27A1 and nuclear receptor-related genes.

This article belongs to the Special Issue Dietary Lipids and Human Health., The bioaccessibility, metabolism, and excretion of lipids composing spent coffee grounds (SCGs) were investigated. An analysis of mycotoxins and an acute toxicity study in rats were performed for safety evaluation. Total fat, fatty acids, and diterpenes (cafestol and kahweol) were determined in SCGs and their digests obtained in vitro. A pilot repeated intake study was carried out in Wistar rats using a dose of 1 g SCGs/kg b.w. for 28 days. Fat metabolism was evaluated by analysis of total fat, cholesterol, and histology in liver. The dietary fiber effect of SCGs was measured radiographically. The absence of mycotoxins and toxicity was reported in SCGs. A total of 77% of unsaturated fatty acids and low amounts of kahweol (7.09 µg/g) and cafestol (414.39 µg/g) were bioaccessible after in vitro digestion. A significantly lower (p < 0.1) accumulation of lipids in the liver and a higher excretion of these in feces was found in rats treated with SCGs for 28 days. No lipid droplets or liver damage were observed by histology. SCGs acutely accelerated intestinal motility in rats. SCGs might be considered a sustainable, safe, and healthy food ingredient with potential for preventing hepatic steatosis due to their effect as dietary fiber with a high fat-holding capacity., This research was funded by the SUSCOFFEE (AGL2014-57239-R) Project.

Maternal supplementation with hydroxytyrosol, a polyphenol present in olive leaves and fruits, is a highly promising strategy to improve the oxidative and metabolic status of fetuses at risk of intrauterine growth restriction, which may diminish the appearance of low-birth-weight neonates. The present study aimed to determine whether hydroxytyrosol, by preventing lipid peroxidation, may influence the fat accretion and energy homeostasis in the liver, as well as the fatty acid composition in the liver and muscle. The results indicate that hydroxytyrosol treatment significantly decreased the energy content of the fetal liver, without affecting fat accretion, and caused significant changes in the availability of fatty acids. There were significant increases in the amount of total polyunsaturated fatty acids, omega-3 and omega-6, which are highly important for adequate fetal tissue development. However, there were increases in the omega-6/omega-3 ratio and the desaturation index, which make further studies necessary to determine possible effects on the pro/anti-inflammatory status of the fetuses., The experimental work was supported by funds from the Ministry of Economy and Competitiveness (project AGL2013–48121-C3-R and AGL2016–79321-C2–2-R), co-funded by FEDER. MVG, CGC, ZP and AHM were backed by the Spanish Government (MVG: FPU National Program Grant Number FPU014/01285. CGC: FPI National Program Grant Number BES-2014-070464. ZP and AHM: FPI National Program Grant Number BES-2017-081486 and BES-2017-080541, respectively).

Cocoa has beneficial health effects partly due to its high flavanol content. This study was aimed at assessing the absorption and metabolism of polyphenols in two soluble cocoa products: a conventional (CC) and a flavanol-rich product (CC-PP). A crossover, randomized, blind study was performed in 13 healthy men and women. On two different days, after an overnight fast, volunteers consumed one serving of CC (15 g) or CC-PP (25 g) in 200 mL of semi-skimmed milk containing 19.80 mg and 68.25 mg of flavanols, respectively. Blood and urine samples were taken, before and after CC and CC-PP consumption, and analyzed by high-performance liquid chromatography coupled to electrospray ionisation and quadrupole time-of-flight mass spectrometry (HPLC-ESI-QToF-MS). Up to 10 and 30 metabolites were identified in plasma and urine, respectively. Phase II derivatives of epicatechin were identified with kinetics compatible with small intestine absorption, although the most abundant groups of metabolites were phase II derivatives of phenyl-&gamma, valerolactone and phenylvaleric acid, formed at colonic level. 5-(4&prime, Hydroxyphenyl)-&gamma, valerolactone-sulfate could be a sensitive biomarker of cocoa flavanol intake. CC and CC-PP flavanols showed a dose-dependent absorption with a recovery of 35%. In conclusion, cocoa flavanols are moderately bioavailable and extensively metabolized, mainly by the colonic microbiota.

Given the emerging evidence of equol&rsquo, s benefit to human health, understanding its synthesis and regulation in equol-producing bacteria is of paramount importance. Adlercreutzia equolifaciens DSM19450T is a human intestinal bacterium &mdash, for which the whole genome sequence is publicly available&mdash, that produces equol from the daidzein isoflavone. In the present work, daidzein (between 50 to 200 &mu, M) was completely metabolized by cultures of A. equolifaciens DSM19450T after 10 h of incubation. However, only about one third of the added isoflavone was transformed into dihydrodaidzein and then into equol. Transcriptional analysis of the ORFs and intergenic regions of the bacterium&rsquo, s equol gene cluster was therefore undertaken using RT-PCR and RT-qPCR techniques with the aim of identifying the genetic elements of equol biosynthesis and its regulation mechanisms. Compared to controls cultured without daidzein, the expression of all 13 contiguous genes in the equol cluster was enhanced in the presence of the isoflavone. Depending on the gene and the amount of daidzein in the medium, overexpression varied from 0.5- to about 4-log10 units. Four expression patterns of transcription were identified involving genes within the cluster. The genes dzr, ddr and tdr, which code for daidzein reductase, dihydrodaidzein reductase and tetrahydrodaidzein reductase respectively, and which have been shown involved in equol biosynthesis, were among the most strongly expressed genes in the cluster. These expression patterns correlated with the location of four putative &rho, independent terminator sequences in the cluster. All the intergenic regions were amplified by RT-PCR, indicating the operon to be transcribed as a single RNA molecule. These findings provide new knowledge on the metabolic transformation of daidzein into equol by A. equolifaciens DSM19450T, which might help in efforts to increase the endogenous formation of this compound and/or its biotechnological production.

Oxidative Balance Scores (OBSs) are tools that have emerged to evaluate the global balance of individuals’ oxidation—reduction status. The aim was to compare OBSs available in the literature regarding their characteristics and associations with chronic diseases in epidemiological studies. Studies that developed OBSs were searched in PubMed until August 2018. A total of 21 OBSs were identified. These OBSs presented di erent scoring schemes and di erent types of anti- and pro-oxidant components, including dietary factors (dietary intake and/or nutrient biomarkers), lifestyle factors, and medications. Most OBSs were based on over 10 components, and some included only dietary factors. Few considered weighted components in the score. Only three OBSs were validated as potential surrogates of oxidative balance through inflammation and OS-related biomarkers. Notably, all the OBSs were associated—to a varying degree—with a reduced risk of cardiovascular diseases, chronic kidney disease, colorectal adenomas, and di erent cancer types (colorectal and breast cancer), as well as with all-cause and cancer-related mortality. For other outcomes, e.g., prostate cancer, contradictory results were reported. In summary, there is a great heterogeneity in the definition of OBSs. Most studies are concordant in supporting that excessive OS reflected by a lower OBS has deleterious e ects on health. Unified criteria for defining the proper OBSs, valuable to gauge OS-related aspects of the diet and lifestyle that may lead to adverse health outcomes, are needed., This research was co-funded by the Health Research Fund (FIS), Acción Estratégica en Salud (AES), of the Spanish Ministry of Economy and Competitiveness, grant number PI12/00002, and the European Regional Development Fund (ERDF).

Edible sprouts with germinating seeds of a few days of age are naturally rich in nutrients and other bioactive compounds. Among them, the cruciferous (Brassicaceae) sprouts stand out due to their high contents of glucosinolates (GLSs) and phenolic compounds. In order to obtain sprouts enriched in these phytochemicals, elicitation is being increasing used as a sustainable practice. Besides, the evidence regarding the bioavailability and the biological activity of these compounds after their dietary intake has also attracted growing interest in recent years, supporting the intake of the natural food instead of enriched ingredients or extracts. Also, there is a growing interest regarding their uses, consumption, and applications for health and wellbeing, in different industrial sectors. In this context, the present review aims to compile and update the available knowledge on the fundamental aspects of production, enrichment in composition, and the benefits upon consumption of diverse edible cruciferous sprouts, which are sources of phenolic compounds and glucosinolates, as well as the evidence on their biological actions in diverse pathophysiological situations and the molecular pathways involved., This work was supported by the Spanish Ministry of Economy and Competitiveness of the Spanish Government through Research Projects, AGL2013-46247-P, the Grant for Research Groups of Excellence from the Murcia Regional Agency for Science and Technology (Fundación Séneca), Project 19900/GERM/15 and a Private Contract with INBAUTEK SL enterprise, RDP was funded by a postdoctoral contract “Juan de la Cierva de Incorporación” (#ICJI-2015-25373) from the Ministry of Economy, Industry and Competitiveness of Spain, and A.A by INBAUTEK SL enterprise., We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI)

BACKGROUND: During early life, dynamic gut colonization and brain development co-occur with potential cross-talk mechanisms affecting behaviour. METHODS: We used 16S rRNA gene sequencing to examine the associations between gut microbiota and neurodevelopmental outcomes assessed by the Bayley Scales of Infant Development III in 71 full-term healthy infants at 18 months of age. We hypothesized that children would differ in gut microbial diversity, enterotypes obtained by Dirichlet multinomial mixture analysis and specific taxa based on their behavioural characteristics. RESULTS: In children dichotomized by behavioural trait performance in above- and below-median groups, weighted Unifrac b-diversity exhibited significant differences in fine motor (FM) activity. Dirichlet multinomial mixture modelling identified two enterotypes strongly associated with FM outcomes. When controlling for maternal pre-gestational BMI and breastfeeding for up to 3 months, the examination of signature taxa in FM groups showed that Turicibacter and Parabacteroides were highly abundant in the below-median FM group, while Collinsella, Coprococcus, Enterococcus, Fusobacterium, Holdemanella, Propionibacterium, Roseburia, Veillonella, an unassigned genus within Veillonellaceae and, interestingly, probiotic Bifidobacterium and Lactobacillus were more abundant in the above-median FM group. CONCLUSIONS: Our results suggest an association between enterotypes and specific genera with FM activity and may represent an opportunity for probiotic interventions relevant to treatment for motor disorders., Spanish Ministry of Innovation and Science, Junta de Andalucía: Excellence Projects (P06-CTS-02341), Spanish Ministry of Economy and Competitiveness (BFU2012-40254-C03-02) and partially funded by the European Commission MyNewGut FP7 EU Project (Grant agreement n◦ 613979), MyNewGut FP7 EU Project (Grant agreement n◦ 613979), DynaHEALTH EU Project HORIZON 2020 (Grant agreement n◦ : 633595-2), Marie Curie post-doctoral fellowship (FP7, no. 329812, NutriOmics), Spanish Ministry of Education, Culture and Sports (FPU16/04587)

&beta, carotene, &alpha, carotene and &beta, cryptoxanthin are greater contributors to vitamin A intake than retinol in the human diet for most people around the world. Their contribution depends on several factors, including bioavailability and capacity of conversion into retinol. There is an increasing body of research showing that the use of retinol activity equivalents or retinol equivalents could lead to the underestimation of the contribution of &beta, cryptoxanthin and of &alpha, carotene. The aim is to assess their apparent bioavailability by comparing concentrations in blood to their dietary intakes and identifying the major food contributors to their dietary intake. Dietary intake (3-day 24-h records) and serum concentrations (by HPLC) were calculated in normolipemic subjects with adequate retinol status (&ge, 1.1 &micro, mol/L) from our studies (n = 633) and apparent bioavailability calculated from 22 other studies (n = 29,700). Apparent bioavailability was calculated as the ratio of concentration in the blood to carotenoid intake. Apparent bioavailabilities for &alpha, cryptoxanthin were compared to those for &beta, carotene. Eating comparable amounts of &alpha, carotene, &beta, cryptoxanthin and &beta, carotene foods resulted in 55% greater &alpha, carotene (95% CI 35, 90) and 686% higher &beta, cryptoxanthin (95% CI 556, 1016) concentrations than &beta, carotene in blood. This suggests differences in the apparent bioavailability of &alpha, cryptoxanthin and even larger differences with &beta, cryptoxanthin, greater than that of &beta, carotene. Four fruits (tomato, orange, tangerine, red pepper) and two vegetables (carrot, spinach) are the main contributors to their dietary intake (&gt, 50%) in Europeans.

This article belongs to the Special Issue Application of Immunonutrient in Human Health and Disease., Moringa oleifera (MO) is a multipurpose plant consumed as food and known for its medicinal uses, among others. Leaves, seeds and pods are the main parts used as food or food supplements. Nutritionally rich and with a high polyphenol content in the form of phenolic acids, flavonoids and glucosinolates, MO has been shown to exert numerous in vitro activities and in vivo effects, including hypoglycemic activity. A systematic search was carried out in the PubMed database and reference lists on the effects of MO on glucose metabolism. Thirty-three animal studies and eight human studies were included. Water and organic solvent extracts of leaves and, secondly, seeds, have been extensively assayed in animal models, showing the hypoglycemic effect, both under acute conditions and in long-term administrations and also prevention of other metabolic changes and complications associated to the hyperglycemic status. In humans, clinical trials are scarce, with variable designs and testing mainly dry leaf powder alone or mixed with other foods or MO aqueous preparations. Although the reported results are encouraging, especially those from postprandial studies, more human studies are certainly needed with more stringent inclusion criteria and a sufficient number of diabetic or prediabetic subjects. Moreover, trying to quantify the bioactive substances administered with the experimental material tested would facilitate comparison between studies., This work was performed under the frame of the NUTRIMOL-DB Project that received funding from the Ministerio de Economía, Industria y Competitividad (MINECO), Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER, UE) (ref. AGL2017-86044-C2-1-R.).

Precision nutrition aims to make dietary recommendations of a more personalized nature possible, to optimize the prevention or delay of a disease and to improve health. Therefore, the characteristics (including sex) of an individual have to be taken into account as well as a series of omics markers. The results of nutritional genomics studies are crucial to generate the evidence needed so that precision nutrition can be applied. Although sex is one of the fundamental variables for making recommendations, at present, the nutritional genomics studies undertaken have not analyzed, systematically and with a gender perspective, the heterogeneity/homogeneity in gene-diet interactions on the different phenotypes studied, thus there is little information available on this issue and needs to be improved. Here we argue for the need to incorporate the gender perspective in nutritional genomics studies, present the general context, analyze the differences between sex and gender, as well as the limitations to measuring them and to detecting specific sex-gene or sex-phenotype associations, both at the specific gene level or in genome-wide-association studies. We analyzed the main sex-specific gene-diet interactions published to date and their main limitations and present guidelines with recommendations to be followed when undertaking new nutritional genomics studies incorporating the gender perspective, This study was partially funded by the Spanish Ministry of Health (Instituto de Salud Carlos III) and the Ministerio de Economía y Competitividad-Fondo Europeo de Desarrollo Regional (FEDER) (grants CIBER 06/03, PRX17/00500, PI16/00366, PI06/1326, and SAF2016–80532-R); the University Jaume I (grants P1–1B2013–54 and COGRUP/2016/06); the Fundació La Marató de TV3 (grant 538/U/2016); the Real Colegio Complutense at Harvard University, the Generalitat Valenciana (grant PROMETEO2017/017 and AEST/2018/044) and by the US Department of Agriculture, Agriculture Research Service (8050–51000-098-00D)

Hearing loss has been recently ranked as the fifth leading cause of years lived with disability, ahead of many other chronic diseases such as diabetes, dementia, or chronic obstructive pulmonary disease. Moreover, according to the World Health Organization, moderate-to-profound hearing loss affects about 466 million people worldwide. Its incidence varies in each population segment, affecting approximately 10% of children and increasing to 30% of the population over 65 years. However, hearing loss receives still very limited research funding and public awareness. This sensory impairment is caused by genetic and environmental factors, and among the latter, the nutritional status has acquired relevance due its association to hearing loss detected in recent epidemiological studies. Several experimental models have proved that the onset and progression of hearing loss are closely linked to the availability of nutrients and their metabolism. Here, we have reviewed studies focused on nutrient effects on auditory function. These studies support the potential of nutritional therapy for the protection against hearing loss progression, which is especially relevant to the aging process and related quality of life., This review was supported by CEU-Banco Santander precompetitive project (MUSPB047) and CEU-Banco Santander consolidation project (MBS18C12) to TP. MINECO (SAF2012-36519) and Instituto de Salud Carlos III (RETIC ARADyAL RD 16/0006/0021) supported MAP contributions., We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI)

Gluten is a complex mixture of storage proteins in cereals like wheat, barley, and rye. Prolamins are the main components of gluten. Their high content in proline and glutamine makes them water-insoluble and difficult to digest in the gastrointestinal tract. Partial digestion generates peptide sequences which trigger immune responses in celiac and gluten-sensitive patients. Gluten detection in food is challenging because of the diversity, in various food matrices, of protein proportions or modifications and the huge number of immunogenic sequences with differential potential immunoactivity. Attempts to develop standard reference materials have been unsuccessful. Recent studies have reported the detection of a limited number of dominant Gluten Immunogenic Peptides (GIP) that share similarities to epitopes presented in the α-gliadin 33-mer, which showed to be highly proteolytic resistant and is considered to be the most immunodominant peptide within gluten in celiac disease (CD). GIP were detectable and quantifiable in very different kind of difficult to analyze food, revealing the potential immunogenicity by detecting T-cell activity of celiac patients. But GIP were also found in stool and urine of celiac patients on a supposedly gluten-free diet (GFD), showing the capacity to resist and be absorbed and excreted from the body, providing the first simple and objective means to assess adherence to the GFD. Methods to specifically and sensitively detect the most active GIP in food and biological fluids are rational candidates may use similar analytical standard references for determination of the immunopathological risk of gluten exposure in gluten-related diseases. España, MINECO AGL2013-48946-C España, Ministerio de Ciencia, Innovación y Universidades y Corporación Tecnológica de Andalucía (CTA)

Mango is a commercially important tropical fruit. During its processing, peel and seed kernel are discarded as waste but they could be recovered as an excellent and cost-effective source of health-promoting ingredients. This study aimed to characterize some of them, including carotenoids like the provitamin A &beta, carotene and lutein, with an interest beyond its role in eye health. Other health-promoting compounds like tocopherols and polyphenols were also evaluated, as well as the in vitro antioxidant capacity of mango by-products. Regarding isoprenoids, &alpha, tocopherol was mainly found in the peels and carotenoids concentration was higher in the pulps. &beta, carotene was the most abundant carotene in pulp and seed kernel, whereas peel was the only source of lutein, with violaxanthin the most abundant xanthophyll in the different mango organs tested. With regard to polyphenols, peels exhibited greater variability in its phenolic composition, being the total content up to 85 and 10 times higher than the pulp and seed kernels, respectively. On the other hand, peels also stood out for being a very rich source of mangiferin. Seed kernels and peels showed higher antioxidant capacity values than the pulps. These results contribute to the valorization of mango by-products as new natural ingredients for the pharma and food industries.

Xanthophylls (lutein, L, zeaxanthin, Z) and anthocyanins are often included in food supplements to improve ocular health. There are no dietary reference intakes for them. The aim was to assess the effects of L, Z and anthocyanin supplementation on short and long-term lutein status markers (serum concentration and macular pigment optical density (MPOD)). Seventy-two postmenopausal women were randomized into a parallel study of 8 months: Group A&mdash, anthocyanines (60 mg/day), Group X&mdash, xanthophylls (6 mg L + 2 mg Z/day), Group X+A&mdash, anthocyanines (60 mg/day) + xanthophylls (6 mg L + 2 mg Z/day). At the beginning of the study, 4 and 8 month serum L and Z concentrations were determined (HPLC), as well as L, Z and anthocyanine dietary intake and MPOD (heterochromic flicker photometry). Baseline concentrations of L (0.35 &plusmn, 0.19 &mu, mol/L), Z (0.11 &plusmn, 0.05 &mu, mol/L), L+Z/cholesterol/triglycerides (0.07 &plusmn, 0.04 &mu, mol/mmol) increased in Group X (2.8- and 1.6-fold in L and Z concentrations) and in group XA (2- and 1.4-fold in L and Z concentrations). MPOD (baseline: 0.32 &plusmn, 0.13 du) was not modified in any of the groups at the end of the study. There were no differences in the dietary intake of L+Z and anthocyanin at any point in time in any group. Supplementation of L and Z at a dietary level provoked an increase in their serum concentration that was not modified by simultaneous supplementation with anthocyanins.

Taurine (TAU) is a sulfur-containing beta amino acid that is not involved in protein composition and anabolism, conditionally essential in mammals provided through diet. Growing evidence supports a protective role of TAU supply in osmoregulation, calcium flux, and reduction of inflammation and oxidant damage in renal diseases like diabetes. Endoplasmic reticulum (ER) stress, due to abnormal proteostasis, is a contributor to nephrotic syndrome and related renal damage. Here, we investigated the effect of dietary TAU (1.5% in drinking water for 15 days) in an established rat model that mimics human minimal change nephrosis, consisting of a single puromycin aminonucleoside (PAN) injection (intraperitoneally 15 mg/100 g body weight), with sacrifice after eight days. TAU limited proteinuria and podocytes foot processes effacement, and balanced slit diaphragm nephrin and glomerular claudin 1 expressions. In cortical proximal tubules, TAU improved lysosomal density, ER perimeter, restored proper ER-mitochondria tethering and mitochondrial cristae, and decreased inflammation. Remarkably, TAU downregulated glomerular ER stress markers (GRP78, GRP94), pro-apoptotic C/EBP homologous protein, activated caspase 3, tubular caspase1, and mitochondrial chaperone GRP75, but maintained anti-apoptotic HSP25. In conclusion, TAU, by targeting upstream ER stress separate from mitochondria dysfunctions at crucial renal sites, might be a promising dietary supplement in the treatment of the drug-resistant nephrotic syndrome., This study was supported by New Pet Food Italia S.r.l. (Italy) donation, ex 60% grants from the University of Brescia (Italy), FFARB 2017, SAF2015-63904-R grant from the Spanish Ministerio de Economía Industria y Competitividad (MINEICO), FEDER funds and MSCA-ITN-2016-721236 from the European Commission H2020-MSCA-ITN program.

It is widely recognized that the intestinal microbiota plays a role in the initiation and perpetuation of intestinal inflammation in numerous chronic conditions. Most studies report intestinal dysbiosis in celiac disease (CD) patients, untreated and treated with a gluten-free diet (GFD), compared to healthy controls. CD patients with gastrointestinal symptoms are also known to have a different microbiota compared to patients with dermatitis herpetiformis and controls, suggesting that the microbiota is involved in disease manifestation. Furthermore, a dysbiotic microbiota seems to be associated with persistent gastrointestinal symptoms in treated CD patients, suggesting its pathogenic implication in these particular cases. GFD per se influences gut microbiota composition, and thus constitutes an inevitable confounding factor in studies conducted in CD patients. To improve our understanding of whether intestinal dysbiosis is the cause or consequence of disease, prospective studies in healthy infants at family risk of CD are underway. These studies have revealed that the CD host genotype selects for the early colonizers of the infant’s gut, which together with environmental factors (e.g., breast-feeding, antibiotics, etc.) could influence the development of oral tolerance to gluten. Indeed, some CD genes and/or their altered expression play a role in bacterial colonization and sensing. In turn, intestinal dysbiosis could promote an abnormal response to gluten or other environmental CD-promoting factors (e.g., infections) in predisposed individuals. Here, we review the current knowledge of host-microbe interactions and how host genetics/epigenetics and environmental factors shape gut microbiota and may influence disease risk. We also summarize the current knowledge about the potential mechanisms of action of the intestinal microbiota and specific components that affect CD pathogenesis., This work was supported by grant AGL2014-52101-P from the Spanish Ministry of Economy and Competitiveness (MINECO). The scholarships to MO from CSIC are fully acknowledged. MCC is a recipient of a Sara Borrell postdoctoral fellowship from the Instituto de Salud Carlos III at the Spanish Ministry of Health (Spain) CD14/00237.

Our group has recently shown the existence of a gut microbial dysbiosis in systemic lupus erythematosus (SLE), supporting previous evidence involving intestinal bacteria in the initiation and amplification of autoimmune diseases. While several studies have addressed the use of dietary fibres to modify intestinal microbiota, information about other correlated components, such as polyphenols, is scarce. The aim of this work was to identify dietary components able to influence this altered microbiota in 20 SLE women and 20 age-matched controls. Food intake was recorded by means of a food frequency questionnaire. The intake of fibres was calculated from Marlett tables, and Phenol-Explorer was used for polyphenol consumption. Results showed positive associations between flavone intake and Blautia, flavanones and Lactobacillus, and dihydrochalcones and Bifidobacterium in the SLE group. Regarding the controls, dihydroflavonols were directly associated with Faecalibacterium, whereas flavonol intake was inversely associated with Bifidobacterium. From the food sources of these polyphenols related to microbiota, orange intake was directly associated with Lactobacillus and apple with Bifidobacterium in SLE, whilst red wine was the best contributor to Faecalibacterium variation. The association between common foods and particular microbial genera, reported to be decreased in SLE, could be of great importance for these patients., This study was financed by European Union FEDER funds and the Spanish Plan Nacional de I+D (grant AGL2010-14952). We are most grateful to the Asociación Lúpicos Asturias (ALAS) and all the volunteers participating in the study. We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI).

Leptin is a hormone crucial in the regulation of food intake and body-weight maintenance. However, the genes and gene variants that influence its plasma levels are still not well known. Results of studies investigating polymorphisms in candidate genes have been inconsistent, and, in addition, very few genome-wide association studies (GWAS) have been undertaken. Our aim was to investigate the genes and gene variants most associated with plasma leptin concentrations in a high-cardiovascular-risk Mediterranean population. We measured plasma leptin in 1011 men and women, and analyzed the genetic factors associated using three approaches: (1) Analyzing the single nucleotide polymorphisms (SNPs) reported in a GWAS meta-analysis in other populations (including an SNP in/near each of these LEP, SLC32A1, GCKR, CCNL, COBLL1, and FTO genes), (2) Investigating additional SNPs in/near those genes, also including the RLEP gene, and (3) Undertaking a GWAS to discover new genes. We did not find any statistically significant associations between the previously published SNPs and plasma leptin (Ln) in the whole population adjusting for sex and age. However, on undertaking an extensive screening of other gene variants in those genes to capture a more complete set of SNPs, we found more associations. Outstanding among the findings was the heterogeneity per sex. We detected several statistically significant interaction terms with sex for these SNPs in the candidate genes. The gene most associated with plasma leptin levels was the FTO gene in men (specifically the rs1075440 SNP) and the LEPR in women (specifically the rs12145690 SNP). In the GWAS on the whole population, we found several new associations at the p &lt, 1 &times, 10&minus, 5 level, among them with the rs245908-CHN2 SNP (p = 1.6 &times, 6). We also detected a SNP*sex interaction at the GWAS significance level (p &lt, 5 &times, 8), involving the SLIT3 gene, a gene regulated by estrogens. In conclusion, our study shows that the SNPs selected as relevant for plasma leptin levels in other populations, are not good markers for this Mediterranean population, so supporting those studies claiming a bias when generalizing GWAS results to different populations. These population-specific differences may include not only genetic characteristics, but also age, health status, and the influence of other environmental variables. In addition, we have detected several sex-specific effects. These results suggest that genomic analyses, involving leptin, should be estimated by sex and consider population-specificity for more precise estimations.

[Background] Own mother’s milk (OMM) is the optimal nutrition for preterm infants. However, pasteurized donor human milk (DHM) is a valid alternative. We explored the differences of the transcriptome in exfoliated epithelial intestinal cells (EEIC) of preterm infants receiving full feed with OMM or DHM., [Methods] The prospective observational study included preterm infants ≤ 32 weeks’ gestation and/or ≤1500 g birthweight. Total RNA from EEIC were processed for genome-wide expression analysis., [Results] Principal component analysis and unsupervised hierarchical clustering analysis revealed two clustered groups corresponding to the OMM and DHM groups that showed differences in the gene expression profile in 1629 transcripts. The OMM group overexpressed lactalbumin alpha gene (LALBA), Cytochrome C oxidase subunit I gene (COX1) and caseins kappa gene (CSN3), beta gene (CSN2) and alpha gene (CSN1S1) and underexpressed Neutrophil Cytosolic Factor 1 gene (NCF1) compared to the DHM group., [Conclusions] The transcriptomic analysis of EEIC showed that OMM induced a differential expression of specific genes that may contribute to a more efficient response to a pro-oxidant challenge early in the postnatal period when preterm infants are at a higher risk of oxidative stress. The use of OMM should be strongly promoted in preterm infants., A.P.-L.: A.G.-R., S.L.-P. and J.K. enjoy research grants CM18/00165, CM16/00174, FI18/0131, CP16/00034 respectively from the Instituto de Investigación Sanitaria Carlos III (Ministry of Science, Innovation and Universities); M.C.C. acknowledges the support from ERC Starting Grant 639226-MAMI from the European Union and also, the Spanish Government of Economy and Competitiveness (MINECO) (AGL2015-707487-P grant). MV a full grant from the RETICS funded by the PN 2018-2021 (Spain), ISCIII- Sub-Directorate General for Research Assessment and Promotion and the European Regional Development Fund (FEDER), reference RD16/0022/0001 and PI17/0131 grant for the IIS Carlos III (Ministry of Science, Innovation and Universities).

Bioactive peptides secreted by probiotic Bifidobacterium longum (peptide B7) and opportunistic pathogen Bacteroides fragilis (peptide B12) modulate the intestinal cytokine milieu in health. Here, we characterized their capacity to modulate both the mucosal cytokine production and the phenotype of circulating antigen presenting cells (APCs) in active inflammatory bowel disease (IBD). The IBD mucosa produced higher levels of pro-inflammatory cytokines referred to healthy controls (HCs). Peptides B7 and B12, however, did not ameliorate the mucosal cytokine milieu in IBD. Human circulating APCs (B-cells, monocytes, plasmacytoid dendritic cells (pDCs), and conventional dendritic cells (cDCs)) were characterized by flow cytometry in presence/absence of the peptides. Circulating B-cells, monocytes, and cDCs from IBD patients were more activated than those from HCs. Peptide B7, but not B12, decreased CCR2 expression on all APC subsets from HC, but not IBD patients. Moreover, both peptides tend to further increase their pro-inflammatory profile in IBD. In summary, IBD patients display mucosal and circulating APC pro-inflammatory properties. Peptide B7 immunomodulatory capacity elicited over circulating APCs from HC, but not IBD patients, suggests the presence of disrupted modulatory mechanisms for this peptide in IBD. Future studies should address the effect of bacteria-derived immunomodulatory peptides in non-inflamed (quiescent) IBD patients., S.F.T. is currently funded by the Instituto de Salud Carlos III (Sara Borrell fellowship CD17/00014). L.O.M. is funded by the Community of Madrid (BMD-5800). D.B. is funded by the Spanish Ministry of Science (RYC-2017-21606). This work was supported by the Spanish Ministry of Economy (SAF2014-56642-JIN), the Spanish Ministry of Health (PIE13/00041), GETECCU (Grupo Español de Trabajo en Enfermedad Crohn y Colitis Ulcerosa), and the Community of Madrid (Consejería de Educación, Juventud y Deporte, Programa de Garantía Juvenil 2015 and 2016).

Epidemiological data suggest that regular intake of isoflavones from soy reduces the incidence of estrogen-dependent and aging-associated disorders, such as menopause symptoms in women, osteoporosis, cardiovascular diseases and cancer. Equol, produced from daidzein, is the isoflavone-derived metabolite with the greatest estrogenic and antioxidant activity. Consequently, equol has been endorsed as having many beneficial effects on human health. The conversion of daidzein into equol takes place in the intestine via the action of reductase enzymes belonging to incompletely characterized members of the gut microbiota. While all animal species analyzed so far produce equol, only between one third and one half of human subjects (depending on the community) are able to do so, ostensibly those that harbor equol-producing microbes. Conceivably, these subjects might be the only ones who can fully benefit from soy or isoflavone consumption. This review summarizes current knowledge on the microorganisms involved in, the genetic background to, and the biochemical pathways of, equol biosynthesis. It also outlines the results of recent clinical trials and meta-analyses on the effects of equol on different areas of human health and discusses briefly its presumptive mode of action., This research was partly funded by grants from the Spanish Ministry of Economy and Competitiveness (MINECO) (AGL2011-24300-ALI and AGL-2014-57820-R) and the Principality of Asturias (GRUPIN14-137 and IDI/2018/000114). L.V. was funded by a contract from MINECO within the FPI Program (BES-2015-072285).

© 2019 by the authors., Nutritional supplements which include natural antitumoral compounds could represent safe and efficient additives for cancer patients. One such nutritional supplement, Ocoxin Oral solution (OOS), is a composite formulation that contains several antioxidants and exhibits antitumoral properties in several in vitro and in vivo tumor conditions. Here, we performed a functional genomic analysis to uncover the mechanism of the antitumoral action of OOS. Using in vivo models of acute myelogenous leukemia (AML, HEL cells, representative of a liquid tumor) and small-cell lung cancer (GLC-8, representative of a solid tumor), we showed that OOS treatment altered the transcriptome of xenografted tumors created by subcutaneously implanting these cells. Functional transcriptomic studies pointed to a cell cycle deregulation after OOS treatment. The main pathway responsible for this deregulation was the E2F–TFDP route, which was affected at different points. The alterations ultimately led to a decrease in pathway activation. Moreover, when OOS-deregulated genes in the AML context were analyzed in patient samples, a clear correlation with their levels and prognosis was observed. Together, these data led us to suggest that the antitumoral effect of OOS is due to blockade of cell cycle progression mainly caused by the action of OOS on the E2F–TFDP pathway., This study was partially supported by the Ministry of Economy and Competitiveness of Spain (BFU2012-39151 and BFU2015-71371-R) and Catalysis S.L. (Madrid, Spain). Our Cancer Research Institute and the work carried out at our laboratory receive support from the European Community through the Regional Development Funding Program (FEDER)

The present work aimed to assess the susceptibility of dominant and representative bacterial populations from the human gut to isoflavones and their metabolites. To do so, the minimum inhibitory concentration (MIC) of isoflavone glycosides, isoflavone aglycones, and equol to 37 bacterial strains was determined by broth microdilution. Additionally, for 10 representative strains, growth curves, growth rate (μ), and optical density (OD600 nm) of the cultures at 24 h were also determined. MICs of daidzin, genistin, daidzein, and genistein were >2048 μg mL−1 for all strains assayed, while that of equol ranged from 16 μg mL−1 for Bifidobacterium animalis subsp. animalis to >2048 μg mL−1 for Enterobacteriaceae strains. Changes in growth curves, μ, and final OD were observed among the species in the presence of all tested compounds. Genistein reduced μ of Bacteroides fragilis, Lactococcus lactis subsp. lactis, and Slackia equolifaciens, while both genistein and equol increased that of Lactobacillus rhamnosus and Faecalibacterium prausnitzii. Compared to controls, lower final OD in the presence of aglycones and equol were recorded for some strains but were higher for others. Altogether, the results suggest that isoflavone-derived compounds could modify numbers of key bacterial species in the gut, which might be associated with their beneficial properties, The study was partially supported by projects from the Spanish Ministry of Economy and Competitiveness (AGL-2014-57820-R) and Asturias Principality (GRUPIN14-137). L.G. and L.V. were supported by research contracts of the FPI Program from MINECO (BES-2012-062502 and BES-2015-072285, respectively).

Diabetes mellitus is associated with reductions in glutathione, supporting the critical role of oxidative stress in its pathogenesis. Antioxidant food components such as flavonoids have a protective role against oxidative stress-induced degenerative and age-related diseases. Flavonoids constitute an important part of the human diet; they can be found in most plant foods, including green tea, grapes or cocoa and possess multiple biological activities. This study investigates the chemo-protective effect of a cocoa phenolic extract (CPE) containing mainly flavonoids against oxidative stress induced by tert-butylhydroperoxide (t-BOOH) on Ins-1E pancreatic beta cells. Cell viability and oxidative status were evaluated. Ins-1E cells treatment with 5–20 μg/mL CPE for 20 h evoked no cell damage and did not alter ROS production. Addition of 50 μM t-BOOH for 2 h increased ROS and carbonyl groups content and decreased reduced glutathione level. Pre-treatment of cells with CPE significantly prevented the t-BOOH-induced ROS and carbonyl groups and returned antioxidant defences to adequate levels. Thus, Ins-1E cells treated with CPE showed a remarkable recovery of cell viability damaged by t-BOOH, indicating that integrity of surviving machineries in the CPE-treated cells was notably protected against the oxidative insult, This work was supported by grants AGL2010-17579 and project CSD2007-00063 from Programa Consolider-Ingenio from the Spanish Ministry of Economy and Competitivity.

The composition of human breast milk is highly variable, and it can be influenced by genetics, diet, lifestyle, and other environmental factors. This study aimed to investigate the impact of geographical location and mode of delivery on the nuclear magnetic resonance spectroscopy (NMR) metabolic profile of breast milk and its relationship with the milk microbiome. Human milk metabolic and microbiota profiles were determined using NMR and 16S rRNA gene sequencing, respectively, in 79 healthy women from Finland, Spain, South Africa, and China. Up to 68 metabolites, including amino acids, oligosaccharides, and fatty acid-associated metabolites, were identified in the milk NMR spectra. The metabolite profiles showed significant differences between geographical locations, with significant differences (p < 0.05) in the levels of galactose, lacto-N-fucopentaose III, lacto-N-fucopentaose I and 2-fucosyllactose, 3-fucosyllactose, lacto-N-difucohexaose II, lacto-N-fucopentaose III, 2-hydroxybutyrate, 3-hydroxybutyrate, proline, N-acetyl lysine, methyl-histidine, dimethylamine, kynurenine, urea, creatine and creatine phosphate, formate, lactate, acetate, phosphocholine, acetylcholine, LDL, VLDL, ethanolamine, riboflavin, hippurate, spermidine, spermine and uridine. Additionally, the effect of caesarean section on milk metabolome was dependent on the geographical region. Specific interrelations between human milk metabolites and microbiota were also identified. Proteobacteria, Actinobacteria, and Bacilli were most significantly associated with the milk metabolites, being either positively or negatively correlated depending on the metabolite. Our results reveal specific milk metabolomic profiles across geographical locations and also highlight the potential interactions between human milk’s metabolites and microbes., This work has been funded by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (ERC Starting Grant, project no. 639226). DM gratefully acknowledges financial support from the JPI HDHL (GUTMOM project) and the Ministerio de Ciencia, Innovación y Universidades from Spain (PCIN-2017-117 and SAF2014-52875R), and also from the ‘Instituto de Salud Carlos III and co-funded by FEDER founds’ (grant number PIE15/00013).