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The two bacterial consortia colonized the intestine of rats and converted UM-0 (non-urolithin-producing) animals into urolithin-producing animals mimicking the UM-A and UM-B metabotypes.

Background: Mexico has declared an epidemiological emergency in the country due to diabetes. Although the benefits of physical activity in middle age are established, the health effects of long-term changes in PA from adolescence to middle age have not been documented. Our aim is to explore the pattern of vigorous physical activity (VPA) in adolescence and adulthood and the risk of DM2 in a cohort of middle-age women. Methods: The Mexican Teacher′s Cohort (MTC) is an ongoing study of 115,307 public school teachers. Every three years participants answered sociodemographic, lifestyle, and medical conditions, including self-reported IPA(hours/wk) for age 15 to18 years, and at the previous year of baseline. Cases of diabetes were identified and validated through electronic health records. We estimated Hazard ratios and IC95% intervals. Based on VPA in adolescence and adulthood respectively, women were classified as: consistently inactive (reference), consistently lower activity, low active in adolescence but increase in adulthood, active in adolescence but reduced in adulthood, and consistently higher. To explore recall bias we performed analyzes stratified by age. Results: in a sample of 69,970 women with 41.6 ± 7.3 years of age at enrolment, we identified 4,564 DM cases from 2006-2008 to 2019. Compared with participants who were consistently inactive in both stages, women who increase activity had a lower risk of DM; HR = 0.86 (95% CI 0.74, 1.01). Compared with the reference category, maintaining higher amounts of VPA was associated with lower diabetes risk HR = 0.85, (95% CI 0.75, 0.96). In stratified analyses by age, we observed the same association even in people who reported physical activity up to 35 years before the reference questionnaire. Conclusions: Maintaining higher VPA levels during adolescence and adulthood and increasing VPA in adulthood were associated with a similar low risk of diabetes.

Proteostasis is a challenge for cellular organisms, as all known protein synthesis machineries are error-prone. Here we show by cell fractionation and microscopy studies that misfolded proteins formed in the endoplasmic reticulum can become associated with and partly transported into mitochondria, resulting in impaired mitochondrial function. Blocking the endoplasmic reticulum-mitochondria encounter structure (ERMES), but not the mitochondrial sorting and assembly machinery (SAM) or the mitochondrial surveillance pathway components Msp1 and Vms1, abrogated mitochondrial sequestration of ER-misfolded proteins. We term this mitochondria-associated proteostatic mechanism for ER-misfolded proteins ERAMS (ER-associated mitochondrial sequestration). We testify to the relevance of this pathway by using mutant α-1-antitrypsin as an example of a human disease-related misfolded ER protein, and we hypothesize that ERAMS plays a role in pathological features such as mitochondrial dysfunction., Sanchón et al find that misfolded proteins formed in the ER can become associated with mitochondria, both in mammalian cells and in yeast, resulting in impaired mitochondrial function. They further discover that components of ERMES-mediated ER-mitochondria contacts are needed for this mechanism, which they name ERAMS, for ER-associated mitochondrial sequestration.

The BINE mobility program has been generating exchange and student mobility experiences since 2010. In the first instance through the Young Teacher Exchange Programme, and subsequently with other teacher training institutions of the DGESPE. The present study considers the following dimensions of the instrument shared by the BINE Mobility Program: Perception of the achievement of the traits of the graduate profile, perception of the subjects taken, general evaluation of the experience, and enrichment comments. The mobility program not only aims at academic improvement but also offers opportunities for future teachers to strengthen their autonomy and become better citizens. The aim of the program in the future should be to move from individual enrichment to genuine institutional development.

Latin America continues to be severely underrepresented in genomics research, and fine-scale genetic histories as well as complex trait architectures remain hidden due to the lack of Big Data. To fill this gap, the Mexican Biobank project genotyped 1.8 million markers in 6,057 individuals from 32 states and 898 sampling localities across Mexico with linked complex trait and disease information creating a valuable nationwide genotype-phenotype database. Through a suite of state-of-the-art methods for ancestry deconvolution and inference of identity-by-descent (IBD) segments, we inferred detailed ancestral histories for the last 200 generations in different Mesoamerican regions, unraveling native and colonial/post-colonial demographic dynamics. We observed large variations in runs of homozygosity (ROH) among genomic regions with different ancestral origins reflecting their demographic histories, which also affect the distribution of rare deleterious variants across Mexico. We analyzed a range of biomedical complex traits and identified significant genetic and environmental factors explaining their variation, such as ROH found to be significant predictors for trait variation in BMI and triglycerides.

Cervical ectopy is a benign condition of the lower genital tract that is frequently detected in women of reproductive age. Although cervical ectopy is regarded as a physiological condition, some women experience symptoms such as leucorrhoea, persistent bleeding and recurrent vaginal infections that require medical intervention. Cervical ectopy has not been linked to cervical cancer, but it is thought to facilitate the acquisition of sexually transmitted diseases (STDs), like Human Papillomavirus (HPV) infection, as it provides a favorable microenvironment for virus infection and dissemination. We and others have described the presence of oncogenic HPV types in women with symptomatic cervical ectopy. The relevance of this finding and the impact of symptomatic cervical ectopy on the cervicovaginal microenvironment (vaginal microbiota, immune and inflammatory responses) are currently unknown. To shed some light into the interplay between HPV, the vaginal microbiota and mucosal immune and inflammatory responses in the context of this condition, we enrolled 156 women with symptomatic cervical ectopy and determined the presence of HPV using a type-specific multiplex genotyping assay. Overall, HPV was detected in 54.48% women, oncogenic HPV types were found in more than 90% of HPV-positive cases. The most prevalent HPV types were HPV16 (29.4%), HPV31 (21.17%) and HPV18 (15.29%). Next, we evaluated the vaginal microbial composition and diversity by 16S rDNA sequencing, and quantified levels of cytokines and chemokines by flow cytometry using bead-based multiplex assays in a sub-cohort of 63 women. IL-21 and CXCL9 were significantly upregulated in HPV-positive women (p=0.0002 and p=0.013, respectively). Women with symptomatic cervical ectopy and HPV infection had increased diversity (pSneathia, Shuttleworthia, Prevotella, and Atopobium) and depleted in Lactobacillus spp. Furthermore, the vaginal microbiota of women with symptomatic cervical ectopy and HPV infection correlated with vaginal inflammation (IL-1β, rho=0.56, p=0.0004) and increased mucosal homeostatic response (IL-22, rho=0.60, p=0.0001). Taken together, our results suggest that HPV infection and dysbiotic vaginal communities could favor a vaginal microenvironment that might delay the recovery of the cervical epithelium in women with symptomatic cervical ectopy and favor STDs acquisition.

Bone marrow mesenchymal stem/stromal cells (BM-MSCs) have immunoregulatory capacity; therefore, they have been used in different clinical protocols in which it is necessary to decrease the immune response. This capacity is mainly regulated by TNF-α and IFN-γ, and it has been observed that cell-cell contact, mainly mediated by ICAM-1, is important for MSCs to carry out efficient immunoregulation. Therefore, in the present work, we analyzed the effect of TNF-α alone or in combination with IFN-γ on the expression of ICAM-1. Besides, given the importance of cell contact in the immunoregulatory function of MSCs, we analyzed whether these cells release ICAM-1+ microvesicles (MVs). Our results show for the first time that TNF-α is capable of increasing the early expression of ICAM-1 in human BM-MSCs. Also, we observed that TNF-α and IFN-γ have a synergistic effect on the increase in the expression of ICAM-1. Furthermore, we found that BM-MSCs exposed to an inflammatory environment release MVs enriched in ICAM-1 (MVs-ICAM-1high). The knowledge generated in this study will contribute to the improvement of in vitro conditioning protocols that favor the therapeutic effect of these cells or their products.

Macrophages with the M2 phenotype promote tumor development through the immunosuppression of antitumor immunity. We previously demonstrated the presence of mesenchymal stem/stromal cells (MSCs) in cervical cancer (CeCa-MSCs), suggesting an immune protective capacity in tumors, but to date, their effect in modulating macrophage polarization remains unknown. In this study, we compared the capacities of MSCs from normal cervix (NCx) and CeCa to promote M2 macrophage polarization in a coculture system. Our results demonstrated that CeCa-MSCs, in contrast to NCx-MSCs, significantly decreased M1 macrophage cell surface marker expression (HLA-DR, CD80, CD86) and increased M2 macrophage expression (CD14, CD163, CD206, Arg1) in cytokine-induced CD14+ monocytes toward M1- or M2-polarized macrophages. Interestingly, compared with NCx-MSCs, in M2 macrophages generated from CeCa-MSC cocultures, we observed an increase in the percentage of phagocytic cells, in the intracellular production of IL-10 and IDO, the capacity to decrease T cell proliferation and for the generation of CD4+CD25+FoxP3+ Tregs. Importantly, this capacity to promote M2 macrophage polarization was correlated with the intracellular expression of macrophage colony-stimulating factor (M-CSF) and upregulation of IL-10 in CeCa-MSCs. Furthermore, the presence of M2 macrophages was correlated with the increased production of IL-10 and IL-1RA anti-inflammatory molecules. Our in vitro results indicate that CeCa-MSCs, in contrast to NCx-MSCs, display an increased M2-macrophage polarization potential and suggest a role of CeCa-MSCs in antitumor immunity.

Urolithins, metabolites produced by the gut microbiota from the polyphenols ellagitannins and ellagic acid, are discovered by the research group in humans almost 20 years ago. Pioneering research suggests urolithins as pleiotropic bioactive contributors to explain the health benefits after consuming ellagitannin-rich sources (pomegranates, walnuts, strawberries, etc.). Here, this study comprehensively updates the knowledge on urolithins, emphasizing the review of the literature published during the last 5 years. To date, 13 urolithins and their corresponding conjugated metabolites (glucuronides, sulfates, etc.) have been described and, depending on the urolithin, detected in different human fluids and tissues (urine, blood, feces, breastmilk, prostate, colon, and breast tissues). There has been a substantial advance in the research on microorganisms involved in urolithin production, along with the compositional and functional characterization of the gut microbiota associated with urolithins metabolism that gives rise to the so-called urolithin metabotypes (UM-A, UM-B, and UM-0), relevant in human health. The design of in vitro studies using physiologically relevant assay conditions (molecular forms and concentrations) is still a pending subject, making some reported urolithin activities questionable. In contrast, remarkable progress has been made in the research on the safety, bioactivity, and associated mechanisms of urolithin A, including the first human interventions., This research was supported by the Project PID2019-103914RB-I00 from the Ministry of Science and Innovation (MICINN, Spain) and the Projects 20880/PI/18 and 19900/GERM/15 (Fundación Séneca de la Región de Murcia, Spain). J.A.G.-B. was supported by a Standard European Marie Curie Fellowship from the European Commission. This project has received funding from the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement no. 838991.

Ebstein's anomaly is a rare complex congenital heart disease, first described in 1866 by physician Wilhelm Ebstein, characterized by anatomical and functional malformations of the tricuspid valve and the right ventricle because of inadequate delaminization of the tricuspid valve tissue. By presenting a clinical case and reviewing the literature, we analyzed the approach of an adult patient with Ebstein anomaly with ventricular preexcitation.We describe the case of a 34-year-old male patient, with a clinical history of palpitations and dyspnea, and his paraclinics documented Ebstein type B anomaly associated with patent foramen oval and paroxysmal supraventricular tachycardia, Successful radiofrequency ablation was performed and tricuspid valvuloplasty was proposed.It is concluded that Ebstein's anomaly is complex with clinical, morphological and physiopathological heterogeneous spectrum. Manifested from severe symptomatic forms in the neonatal period to asymptomatic or minimally symptomatic ones detected incidentally. Its diagnosis is based on clinical suspicion and confirmed by echocardiography or imaging studies. The therapeutic strategy may be based on medical management in its mild asymptomatic forms up to surgical interventions that include tricuspid valvuloplasty, palliative surgery, valve replacement or cardiac transplantation.la anomalía de Ebstein es una cardiopatía congénita compleja infrecuente, descrita por primera vez en 1866 por el médico Wilhelm Ebstein, caracterizada por malformaciones anatómicas y funcionales de la válvula tricúspide y del ventrículo derecho a consecuencia de una inadecuada deslaminización del tejido valvular tricuspídeo. Mediante la presentación de caso clínico y revisión de la literatura analizamos el abordaje de un paciente adulto con anomalía de Ebstein con preexcitación ventricular.describimos el caso de un paciente masculino de 34 años, con historial clínico de palpitaciones y disnea, en sus paraclínicos se documentó anomalía de Ebstein tipo B asociado a foramen oval permeable y taquicardia paroxística supraventricular, como tratamiento se realizó ablación por radiofrecuencia exitosa y proponiéndose valvuloplastia tricuspídea.la anomalía de Ebstein es compleja de espectro clínico, morfológico y fisiopatológico heterogéneo, manifestada desde formas graves sintomáticas en el periodo neonatal hasta asintomáticas o mininamente sintomáticas detectadas de forma incidental. Su diagnóstico parte de la sospecha clínica confirmándose a partir de ecocardiografía o estudios de imagen. La estrategia terapéutica puede estar basada en manejo médico en sus formas leves asintomáticas hasta intervenciones quirúrgicas que incluyen valvulo-plastia tricuspídea, cirugía paliativa, reemplazo valvular o trasplante cardiaco.

Mitochondrial misreading, conferred by mutation V338Y in mitoribosomal protein Mrps5, in-vivo is associated with a subtle neurological phenotype. Brain mitochondria of homozygous knock-in mutant Mrps5V338Y/V338Y mice show decreased oxygen consumption and reduced ATP levels. Using a combination of unbiased RNA-Seq with untargeted metabolomics, we here demonstrate a concerted response, which alleviates the impaired functionality of OXPHOS complexes in Mrps5 mutant mice. This concerted response mitigates the age-associated decline in mitochondrial gene expression and compensates for impaired respiration by transcriptional upregulation of OXPHOS components together with anaplerotic replenishment of the TCA cycle (pyruvate, 2-ketoglutarate)., International Journal of Molecular Sciences, 22 (5), ISSN:1422-0067

The maternal-infant transmission of several urolithins through breast milk and the gut colonization of infants by the urolithin-producing bacterium

© 2020 by the authors., The gut microbiota (GM) has attracted attention as a new target to combat several diseases, including metabolic syndrome (MetS), a pathological condition with many factors (diabetes, obesity, dyslipidemia, hypertension, etc.) that increase cardiovascular disease (CVD) risk. However, the existence of a characteristic taxonomic signature associated with obesity-related metabolic dysfunctions is under debate. To investigate the contribution of the CVD risk factors and(or) their associated drug treatments in the composition and functionality of GM in MetS patients, we compared the GM of obese individuals (n = 69) vs. MetS patients (n = 50), as well as within patients, depending on their treatments. We also explored associations between medication, GM, clinical variables, endotoxemia, and short-chain fatty acids. Poly-drug treatments, conventional in MetS patients, prevented the accurate association between medication and GM profiles. Our results highlight the heterogeneity of taxonomic signatures in MetS patients, which mainly depend on the CVD risk factors. Hypertension and(or) its associated medication was the primary trait involved in the shaping of GM, with an overabundance of lipopolysaccharide-producing microbial groups from the Proteobacteria phylum. In the context of precision medicine, our results highlight that targeting GM to prevent and(or) treat MetS should consider MetS patients more individually, according to their CVD risk factors and associated medication., This research was funded by MINECO (Spain), grant number AGL2015-64124-R, and Fundación Séneca de la Región de Murcia (Spain), grant number 20880/PI/18. A.C.M. is the holder of a predoctoral grant from MINECO (Spain).

Dietary (poly)phenols are extensively metabolized, limiting their anticancer activity. Exosomes (EXOs) are extracellular vesicles that could protect polyphenols from metabolism. Our objective was to compare the delivery to breast tissue and anticancer activity in breast cancer cell lines of free curcumin (CUR) and resveratrol (RSV) vs. their encapsulation in milk-derived EXOs (EXO-CUR and EXO-RSV). A kinetic breast tissue disposition was performed in rats. CUR and RSV were analyzed using UPLC-QTOF-MS and GC-MS, respectively. Antiproliferative activity was tested in MCF-7 and MDA-MB-231 breast cancer and MCF-10A non-tumorigenic cells. Cell cycle distribution, apoptosis, caspases activation, and endocytosis pathways were determined. CUR and RSV peaked in the mammary tissue (41 ± 15 and 300 ± 80 nM, respectively) 6 min after intravenous administration of EXO-CUR and EXO-RSV, but not with equivalent free polyphenol concentrations. Nanomolar EXO-CUR or EXO-RSV concentrations, but not free CUR or RSV, exerted a potent antiproliferative effect on cancer cells with no effect on normal cells. Significant (p < 0.05) cell cycle alteration and pro-apoptotic activity (via the mitochondrial pathway) were observed. EXO-CUR and EXO-RSV entered the cells primarily via clathrin-mediated endocytosis, avoiding ATP-binding cassette transporters (ABC). Milk EXOs protected CUR and RSV from metabolism and delivered both polyphenols to the mammary tissue at concentrations compatible with the fast and potent anticancer effects exerted in model cells. Milk EXOs enhanced the bioavailability and anticancer activity of CUR and RSV by acting as Trojan horses that escape from cancer cells’ ABC-mediated chemoresistance.

Understanding individuals' response to dietary bioactives is crucial for personalized nutrition. We report here for the first time in a Caucasian cohort (5-90 years, n = 839) that aging is the main factor that determines the gut microbiota involved in the ellagic acid-ellagitannin metabolism (urolithin metabotypes), with potential consequences for human health.

The monohydration of SO2 has been achieved in solution mediated by a platinum-aquo complex. Benzamidate ligands play a key role along the process, acting as versatile proton shuttles. Finally, the platinum center allows the stabilization of benzimidic acid and a hydrogensulphite anion, the disfavored tautomers of benzamide and sulphonate, respectively., This work was supported by the Spanish MINECO/FEDER (Project CTQ2015-67461-P) and the Gobierno de Aragón and Fondo Social Europeo (Grupo de referencia E17_17R: Química Inorgánica y de los Compuestos Organometálicos).

Environmental and genetic factors are associated with pandemic obesity since childhood. However, the association of overweight-obesity with these factors, acting as a consortium, has been scarcely studied in children. We aimed here to assess the probabilities of being overweighed-obese in a randomly recruited cohort of Spanish children and adolescents (n = 415, 5−17 years-old) by estimating the odds ratios for different predictor variables, and their relative importance in the prediction. The predictor variables were ethnicity, age, sex, adherence to the Mediterranean diet (KIDMED), physical activity, urolithin metabotypes (UM-A, UM-B and UM-0) as biomarkers of the gut microbiota, and 53 single-nucleotide polymorphisms (SNPs) from 43 genes mainly related to obesity and cardiometabolic diseases. A proportional-odds logistic ordinal regression, validated through bootstrap, was used to model the data. While every variable was not independently associated with overweight-obesity, however, the ordinal logistic model revealed that overweight-obesity prevalence was related to being a young boy with either UM-B or UM-0, low KIDMED score and high contribution of a consortium of 24 SNPs, being rs1801253-ADRB1, rs4343-ACE, rs8061518-FTO, rs1130864-CRP, rs659366-UCP2, rs6131-SELP, rs12535708-LEP, rs1501299-ADIPOQ, rs708272-CETP and rs2241766-ADIPOQ the top-ten contributing SNPs. Additional research should confirm and complete this model by including dietary interventions and the individuals’ gut microbiota composition., This research was funded by the Project AGL2015-64124-R (MINECO, Spain). A.C.-M. is the holder of a FPI predoctoral grant from MINECO (Spain).

The metabolism of dietary polyphenols ellagitannins by the gut-microbiota allows the human stratification in urolithin metabotypes depending on the final urolithins produced. Metabotype-A only produces urolithin-A, metabotype-B yields urolithin-B and isourolithin-A in addition to urolithin-A, and metabotype 0 does not produce urolithins. Metabotype-A has been suggested to be &lsquo, protective&rsquo, and metabotype-B dysbiotic-prone to cardiometabolic impairments. We analyzed the gut-microbiome of 40 healthy women and determined their metabotypes and enterotypes, and their associations with anthropometric and gut-microbial changes after 3 weeks, 4, 6, and 12 months postpartum. Metabotype-A was predominant in mothers who lost weight (&ge, 2 kg) (75%) versus metabotype-B (54%). After delivery, the microbiota of metabotype-A mothers changed, unlike metabotype-B, which barely changed over 1 year. The metabotype-A discriminating bacteria correlated to the decrease of the women&rsquo, s waist while some metabotype-B bacteria were inversely associated with a reduction of body mass index (BMI), waist, and waist-to-hip ratio. Metabotype-B was associated with a more robust and less modulating microbial and anthropometric profiles versus metabotype-A, in which these profiles were normalized through the 1-year follow-up postpartum. Consequently, urolithin metabotypes assessment could be a tool to anticipate the predisposition of women to normalize their anthropometric values and gut-microbiota, significantly altered during pregnancy and after childbirth.

Scope: Poly-pharmacological therapy shapes the gut microbiota (GM) in metabolic syndrome (MetS) patients. The effects of polyphenols in poly-medicated MetS patients are unknown. Methods and results: A randomized, placebo-controlled, double-blinded, and crossover trial in poly-medicated MetS patients (n=50) explored whether the effects of a pomegranate extract nutraceutical (PE, 320 mg phenolics/day for 1 month) are affected by the drug therapy. Considering the lipid-lowering (LL-), anti-hypertensive (HP-) and(or) anti-diabetic (AD-) treatments: GM (16S rRNA sequencing), short-chain fatty acids, 40 inflammatory-metabolic and endotoxemia-related biomarkers, associations between biomarkers and GM with 53 cardiometabolic dysfunctions-related single-nucleotide polymorphisms (SNPs), and urolithin metabotypes (UMs) influence are evaluated. Representative SNPs-GM associations after PE include Lactococcus and ClostridiumXIVa with rs5443-GNB3 (G-protein-β-polypeptide-3) and ClostridiumXIVa with rs7903146-TCF7L2 (transcription-factor-7-like-2) and rs1137101-LEPR (leptin-receptor). PE decreases sICAM-1 in LL-patients and the lipopolysaccharide-binding protein in all the patients. PE does not affect the other patients’ markers as a group or stratifying by UMs. After PE, Lactococcus increases in AD-, LL-, and HP-patients, Bifidobacterium increases in LL- and AD-, while Clostridium XIVa decreases in non-LL- and non-HP-patients. Conclusion: The prebiotic effect of PE depends on the medication, mainly on HP-treatments. Targeting GM can complement MetS therapy, but the patients’ drug therapy should be considered individually., Ministerio de Economía y Competitividad. Grant Number: AGL2015-94124-R Fundación Séneca. Grant Number: 20880/PI/18 Ministerio de Ciencia e Innovación. Grant Number: PID2019-103914RB-I00

Human mesenchymal stem cells (MSCs) are good candidates for brain cell replacement strategies and have already been used as adjuvant treatments in neurological disorders. MSCs can be obtained from many different sources, and the present study compares the potential of neuronal transdifferentiation in MSCs from adult and neonatal sources (Wharton’s jelly (WhJ), dental pulp (DP), periodontal ligament (PDL), gingival tissue (GT), dermis (SK), placenta (PLAC), and umbilical cord blood (UCB)) with a protocol previously tested in bone marrow- (BM-) MSCs consisting of a cocktail of six small molecules: I-BET151, CHIR99021, forskolin, RepSox, Y-27632, and dbcAMP (ICFRYA). Neuronal morphology and the presence of cells positive for neuronal markers (TUJ1 and MAP2) were considered attributes of neuronal induction. The ICFRYA cocktail did not induce neuronal features in WhJ-MSCs, and these features were only partial in the MSCs from dental tissues, SK-MSCs, and PLAC-MSCs. The best response was found in UCB-MSCs, which was comparable to the response of BM-MSCs. The addition of neurotrophic factors to the ICFRYA cocktail significantly increased the number of cells with complex neuron-like morphology and increased the number of cells positive for mature neuronal markers in BM- and UCB-MSCs. The neuronal cells generated from UCB-MSCs and BM-MSCs showed increased reactivity of the neuronal genes TUJ1, MAP2, NF-H, NCAM, ND1, TAU, ENO2, GABA, and NeuN as well as down- and upregulation of MSC and neuronal genes, respectively. The present study showed marked differences between the MSCs from different sources in response to the transdifferentiation protocol used here. These results may contribute to identifying the best source of MSCs for potential cell replacement therapies.

The full consensus on the role of dietary polyphenols as human-health-promoting compounds remains elusive. The two-way interaction between polyphenols and gut microbiota (GM) (i.e., modulation of GM by polyphenols and their catabolism by the GM) is determinant in polyphenols' effects. The identification of human metabotypes associated with a differential gut microbial metabolism of polyphenols has opened new research scenarios to explain the inter-individual variability upon polyphenols consumption. The metabotypes unequivocally identified so far are those involved in the metabolism of isoflavones (equol and(or) O-desmethylangolesin producers versus non-producers) and ellagic acid (urolithin metabotypes, including producers of only urolithin-A (UM-A), producers of urolithin-A, isourolithin-A, and urolithin-B (UM-B), and non-producers (UM-0)). In addition, the microbial metabolites (phenolic-derived postbiotics) such as equol, urolithins, valerolactones, enterolactone, and enterodiol, and 8-prenylnaringenin, among others, can exert differential health effects. The knowledge is updated and position is taken here on i) the two-way interaction between GM and polyphenols, ii) the evidence between phenolic-derived postbiotics and health, iii) the role of metabotypes as biomarkers of GM and the clustering of individuals depending on their metabotypes (metabotyping) to explain polyphenols' effects, and iv) the gut microbial metabolism of catecholamines to illustrate the intersection between personalized nutrition and precision medicine.

The monohydration of SO2 has been achieved in solution mediated by a platinum-aquo complex. Benzamidate ligands play a key role along the process, acting as versatile proton shuttles. Finally, the platinum center allows the stabilization of benzimidic acid and a hydrogensulphite anion, the disfavored tautomers of benzamide and sulphonate, respectively.

Scope The gut microbiota ellagitannin-metabolizing phenotypes (i.e., urolithin metabotypes [UMs]) are proposed as potential cardiovascular disease (CVD) risk biomarkers because the host blood lipid profile is reported to be associated with specific UMs. However, the link for this association remains unknown so far. Methods and results The gut microbiome of 249 healthy individuals is analyzed using 16S rDNA sequencing analysis. Individuals are also stratified by UMs (UM-A, UM-B, and UM-0) and enterotypes (Bacteroides, Prevotella, and Ruminococcus). Associations of UMs discriminating bacteria with CVD risk markers are investigated. Distribution and gut microbiota composition of UMs and enterotypes are not coincident. Almost half of the discriminating genera between UM-A and UM-B belongs to the Coriobacteriaceae family. UM-B individuals present higher blood cholesterol levels and higher alpha-diversity, including Coriobacteriaceae family, than those of UM-A. Coriobacteriaceae, whose abundance is the highest in UM-B, is positively correlated with total cholesterol, LDL cholesterol, and body mass index. Conclusions Results herein suggest that the family Coriobacteriaceae could be a link between individuals' UMs and their blood cholesterol levels. Further research is needed to explore the mechanisms of the host metabolic phenotype, including cholesterol excretion products, to modulate this bacterial family.

SCOPE: The stratification of individuals according to their gut microbiota metabotypes is crucial to understand the polyphenols health effects as reported for isoflavones and ellagitannins. To date, the existence of human gut microbiota metabotypes associated with proanthocyanidins (PAs) catabolism remains unclear. METHODS & RESULTS: Sixty‐eight healthy volunteers (40 adolescents and 28 adults) consumed a mixture of walnuts, almonds, and hazelnuts for 3 days, providing 163.65 ± 11.74 mg of PAs. Urine samples were analyzed by ultra‐performance LC–ESI‐quadrupole time‐of‐flight. Twenty‐one isomers of conjugated valerolactones and valeric acids were identified, which derived from six valerolactone and valeric acid precursors after analysis of hydrolyzed urine. This combined approach allowed discrimination between the inter‐individual variability related to phase‐II enzymes polymorphisms and the metabolism of PAs by the gut microbiota. No associations of PAs metabolism with gender, age, BMI, or ellagitannin metabotypes were found. Different quantitative excretion was observed after multivariate analysis but not true gut microbiota metabotypes associated with PAs catabolism. CONCLUSIONS: The metabolism of PAs does not reveal urinary metabolites consistent with distinctive gut microbiota metabotypes. The quantitative excretion of metabolites is inadequate to stratify individuals due to the strong influence of external factors (source, quantity, and time of the last intake of PAs, etc.).

SCOPE: Gut microbiota dysbiosis, intestinal barrier failure, obesity, metabolic endotoxemia, and pro‐inflammatory status promote cardiovascular risk. However, the modulation of the gut microbiome to prevent endotoxemia in obesity has been scarcely studied. We investigated the association between gut microbiota modulation and plasma lipopolysaccharide‐binding protein (LBP), a surrogate marker of endotoxemia, in overweight‐obese individuals. METHODS AND RESULTS: In a randomized trial, 49 overweight‐obese subjects (body mass index> 27 kg m⁻²) with mild hypelipidemia daily consumed, in a cross‐over fashion, two doses (D1 and D2, lasting 3 weeks each) of pomegranate extract (PE) or placebo alternating with 3 weeks of wash‐out periods. A significant decrease (p < 0.05) of plasma LBP and a marginal decrease (p = 0.054) of high‐sensitivity C‐reactive protein were observed, but only after PE‐D2 administration (656 mg phenolics). 16S rDNA sequencing analyses revealed the increase of microorganisms important for maintaining normal balance of gut microbiota and gut barrier function, particularly Bacteroides, Faecalibacterium, Butyricicoccus, Odoribacter, and Butyricimonas. PE‐D2 also decreased pro‐inflammatory microorganisms including Parvimonas, Methanobrevibacter, and Methanosphaera. Remarkably, plasma LBP reduction was significantly associated (p < 0.05) with both Faecalibacterium and Odoribacter increase and Parvimonas decrease. CONCLUSIONS: Consumption of PE decreased endotoxemia in overweight‐obese individuals by reshaping the gut microbiota, mainly through the modulation of Faecalibacterium, Odoribacter, and Parvimonas.

Bone marrow mesenchymal stem/stromal cells (BM-MSCs) have immunoregulatory properties and have been used as immune regulators for the treatment of graft-versus-host disease (GVHD). Human dental tissue mesenchymal stem cells (DT-MSCs) constitute an attractive alternative to BM-MSCs for potential clinical applications because of their accessibility and easy preparation. The aim of this in vitro study was to compare MSCs from dental pulp (DP-MSCs), gingival tissue (G-MSCs), and periodontal ligament (PDL-MSCs) in terms of their immunosuppressive properties against lymphoid cell populations enriched for CD3+ T cells to determine which MSCs would be the most appropriate for in vivo immunoregulatory applications. BM-MSCs were included as the gold standard. Our results demonstrated, in vitro, that MSCs from DP, G, and PDL showed immunoregulatory properties similar to those from BM, in terms of the cellular proliferation inhibition of both CD4+- and CD8+-activated T-cells. This reduced proliferation in cell co-cultures correlated with the production of interferon-&gamma, and tumor necrosis factor alpha (TNF-&alpha, ) and the upregulation of programmed death ligand 1 (PD-L1) in MSCs and cytotoxic T-cell-associated Ag-4 (CTLA-4) in T-cells and increased interleukin-10 and prostaglandin E2 production. Interestingly, we observed differences in the production of cytokines and surface and secreted molecules that may participate in T-cell immunosuppression in co-cultures in the presence of DT-MSCs compared with BM-MSCs. Importantly, MSCs from four sources favored the generation of T-cell subsets displaying the regulatory phenotypes CD4+CD25+Foxp3+ and CD4+CD25+CTLA-4+. Our results in vitro indicate that, in addition to BM-MSCs, MSCs from all of the dental sources analyzed in this study might be candidates for future therapeutic applications.

The purpose of this study was to determine the frequency of emerging parasites in two groups of immunosuppressed patients, including individuals infected with the human immunodeficiency virus (AIDS) (HIV) or having acute lymphoblastic leukemia (ALL) with or without diarrhea. Stool samples were collected from 96 HIV and 77 ALL patients from March 2010 through December 2011. Screening for opportunistic parasites was carried out by the coproparasitoscopic Faust method, Ziehl Neelsen staining, and Polymerase Chain Reaction (PCR). Results showed that 22.9% of HIV fecal samples were positive for emerging parasites, including Cryptosporidium spp. (7.3%), Microsporidium spp. (5.2%), Isospora belli (1.0%), Giardia intestinalis (2.6%), and Cyclospora spp. (7.3%). On the other hand, 32.5% of ALL fecal samples were positive for emerging parasites, including Cryptosporidium spp. (9.1%), Microsporidium spp. (19.5%), Isospora belli (1.3%), and Giardia intestinalis (2.6%). Our results highlighted the need for specific, efficient, and reliable diagnostic methods to identify the presence of emerging parasites in immunocompromised patients susceptible to different infectious diseases or neoplastic processes and avoid the consequences for the host as an increased disease rate, alterations in the clinical manifestation of the infection or even exacerbation of its course.

The purpose of this investigation was to determine the intestinal parasite prevalence in puppies from six different kennels; four kennels were in Guadalajara and Zapopan cities (Jalisco State) and two kennels were in Mexico City. From October 2006 to November 2007, we collected 441 fecal samples from 147 puppies, both male and female, ranging from 1 to 36 months of age. Three samples from every puppy were analyzed by using the Faust technique. The prevalence found were as follows: Giardia intestinalis (genotype A and B) 6.8%; Cystoisospora 21.08%; Uncinaria 7.48%; Toxocara canis 12.29% and multiparasitism (Giardia, Toxocara and Uncinaria) 4.76%. The highest prevalence for both Giardia and Cystoisospora were found in 2-3- month-old puppies; the highest prevalence for Toxocara canis was found in 3-4-month-old puppies. In the kennels of Mexico City we found mainly Giardia intestinalis, Cystoisospora to be most prevalent in Zapopan and Toxocara canis in Guadalajara. The high prevalence of intestinal parasites found in this study demonstrates an increased risk for infection in humans, as these animals are usually a common pet in many homes. This zoonotic phenomenon represents an important health problem for any community.