The Role of Probiotics and Prebiotics in the Prevention and Treatment of Obesity

Obesity is a global pandemic complex to treat due to its multifactorial pathogenesis—an unhealthy lifestyle, neuronal and hormonal mechanisms, and genetic and epigenetic factors are involved. Scientific evidence supports the idea that obesity and metabolic consequences are strongly related to changes in both the function and composition of gut microbiota, which exert an essential role in modulating energy metabolism. Modifications of gut microbiota composition have been associated with variations in body weight and body mass index. Lifestyle modifications remain as primary therapy for obesity and related metabolic disorders. New therapeutic strategies to treat/prevent obesity have been proposed, based on pre- and/or probiotic modulation of gut microbiota to mimic that found in healthy non-obese subjects. Based on human and animal studies, this review aimed to discuss mechanisms through which gut microbiota could act as a key modifier of obesity and related metabolic complications. Evidence from animal studies and human clinical trials suggesting potential beneficial effects of prebiotic and various probiotic strains on those physical, biochemical, and metabolic parameters related to obesity is presented. As a conclusion, a deeper knowledge about pre-/probiotic mechanisms of action, in combination with adequately powered, randomized controlled follow-up studies, will facilitate the clinical application and development of personalized healthcare strategies.Supported by funds from European Union 7th FP KBBE.2013.2.2-02—MyNewGut Project (“Factors influencing the human gut microbiome and its effect on the development of diet-related diseases and brain development”, Grant Agreement 613979) and from Spanish Ministry of Economy and Competitiveness GD-Brain Projects (SAF2015-69265-c2.2)

Influence of a Functional Nutrients-Enriched Infant Formula on Language Development in Healthy Children at Four Years Old

Nutrition during early life is essential for brain development and establishes the basis for cognitive and language skills development. It is well established that breastfeeding, compared to formula feeding, has been traditionally associated with increased neurodevelopmental scores up to early adulthood. We analyzed the long-term effects of a new infant formula enriched with bioactive compounds on healthy children’s language development at four years old. In a randomized double-blind COGNIS study, 122 children attended the follow-up call at four years. From them, 89 children were fed a standard infant formula (SF, n = 46) or an experimental infant formula enriched with functional nutrients (EF, n = 43) during their first 18 months of life. As a reference group, 33 exclusively breastfed (BF) were included. Language development was assessed using the Oral Language Task of Navarra-Revised (PLON-R). ANCOVA, chi-square test, and logistic regression models were performed. EF children seemed to show higher scores in use of language and oral spontaneous expression than SF children, and both SF and EF groups did not differ from the BF group. Moreover, it seems that SF children were more frequently categorized into “need to improve and delayed” in the use of language than EF children, and might more frequently present “need to improve and delayed” in the PLON-R total score than BF children. Finally, the results suggest that SF children presented a higher risk of suffering language development than BF children. Secondary analysis also showed a slight trend between low socioeconomic status and poorer language skills. The functional compound-enriched infant formula seems to be associated with beneficial long-term effects in the development of child’s language at four years old in a similar way to breastfed infants.This project has been funded by Ordesa Laboratories, S.L. Contract University of Granada General Foundation, No. 3349 and SMARTFOODS (CIEN) Contract University of Granada General Foundation, No. 4003, Spanish Ministry of Economy, Industry and Competitiveness; funded in part by HORIZON 2020 EU DynaHEALTH Project (GA No.633595). Natalia Sepúlveda-Valbuena has been granted with a scholarship from Fundación Carolina, Madrid, Spai

Cortical Visual Evoked Potentials and Growth in Infants Fed with Bioactive Compounds-Enriched Infant Formula: Results from COGNIS Randomized Clinical Trial

Postnatal nutrition is essential for growth and neurodevelopment. We analyzed the influence of a new enriched-infant formula with bioactive compounds on growth, neurodevelopment, and visual function (VF) in healthy infants during their first 18 months of life. A total of 170 infants were randomized in the COGNIS randomized clinical trial (RCT) to receive a standard infant formula (SF = 85) or a new experimental infant formula supplemented with functional nutrients (EF = 85). As a control, 50 breastfed infants (BF) were enrolled. Growth patterns were evaluated up to 18 months of life; neurodevelopment was assessed by general movements at 2, 3, and 4 months; VF was measured by cortical visual evoked potentials at 3 and 12 months. No differences in growth and neurodevelopment were found between groups. Regarding VF, SF and EF infants presented prolonged latencies and lower amplitudes in the P100 wave than BF infants. In the EF group, a higher percentage of infants presented response at 7 1/2' of arc at 12 months compared to 3 months of age; a similar proportion of BF and EF infants presented responses at 7 1/2' of arc at 12 months of age. Early nutritional intervention with bioactive compounds could narrow the gap in growth and neurodevelopment between breastfed and formula-fed infants.This project has been funded by Ordesa Laboratories, S.L. Contract University of Granada General Foundation, No. 3349 and SMARTFOODS (CIEN) Contract University of Granada General Foundation, No. 4003, Spanish Ministry of Economy, Industry and Competitiveness; funded in part by HORIZON 2020 EU DynaHEALTH Project (GA No.633595)

Infant Formula Supplemented With Milk Fat Globule Membrane, Long-Chain Polyunsaturated Fatty Acids, and Synbiotics Is Associated With Neurocognitive Function and Brain Structure of Healthy Children Aged 6 Years: The COGNIS Study

Background: Adequate nutrient intake during the first few months of life plays a critical role on brain structure and function development. Objectives: To analyze the long-term effects of an experimental infant formula (EF) on neurocognitive function and brain structure in healthy children aged 6 years compared to those fed with a standard infant formula or breastfed. Methods: The current study involved 108 healthy children aged 6 years and participating in the COGNIS Study. At 0-2 months, infants were randomized to receive up to 18 months of life a standard infant formula (SF) or EF enriched with milk fat globule membrane (MFGM), long-chain polyunsaturated fatty acids (LC-PUFAs) and synbiotics. Furthermore, a reference group of breastfed (BF) infants were also recruited. Children were assessed using neurocognitive tests and structural Magnetic Resonance Imaging (MRI) at 6 years old. Results: Experimental infant formula (EF) children showed greater volumes in the left orbital cortex, higher vocabulary scores and IQ, and better performance in an attention task than BF children. EF children also presented greater volumes in parietal regions than SF kids. Additionally, greater cortical thickness in the insular, parietal, and temporal areas were found in children from the EF group than those fed with SF or BF groups. Further correlation analyses suggest that higher volumes and cortical thickness of different parietal and frontal regions are associated with better cognitive development in terms of language (verbal comprehension) and executive function (working memory). Finally, arachidonic acid (ARA), adrenic acid (AdA), docosahexaenoic acid (DHA) levels in cheek cell glycerophospholipids, ARA/DHA ratio, and protein, fatty acid, and mineral intake during the first 18 months of life seem to be associated with changes in the brain structures at 6 years old. Conclusions: Supplemented infant formula with MFGM components, LC-PUFAs, and synbiotics seems to be associated to long-term effects on neurocognitive development and brain structure in children at 6 years old.This project has been funded by Laboratorios Ordesa, S.L. Contract University of Granada General Foundation, No. 3349 and SMARTFOODS (CIEN) Contract University of Granada General Foundation, No. 4003, Spanish Ministry of Economy, Industry and Competitiveness. Furthermore, the project has been partially funded by HORIZON 2020 EU DynaHEALTH Project (GA No. 633595).S

SMAD3 rs17228212 Gene Polymorphism Is Associated with Reduced Risk to Cerebrovascular Accidents and Subclinical Atherosclerosis in Anti-CCP Negative Spanish Rheumatoid Arthritis Patients

Rheumatoid arthritis (RA) is a complex polygenic inflammatory disease associated with accelerated atherosclerosis and increased risk of cardiovascular (CV) disease. Previous genome-wide association studies have described SMAD3 rs17228212 polymorphism as an important signal associated with CV events. The aim of the present study was to evaluate for the first time the relationship between this gene polymorphism and the susceptibility to CV manifestations and its potential association with the presence of subclinical atherosclerosis assessed by the evaluation of carotid intima-media thickness (cIMT) in patients with RA

RICORS2040 : The need for collaborative research in chronic kidney disease

Chronic kidney disease (CKD) is a silent and poorly known killer. The current concept of CKD is relatively young and uptake by the public, physicians and health authorities is not widespread. Physicians still confuse CKD with chronic kidney insufficiency or failure. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. Thus health authorities may consider CKD a non-issue: very few persons eventually need KRT and, for those in whom kidneys fail, the problem is 'solved' by dialysis or kidney transplantation. However, KRT is the tip of the iceberg in the burden of CKD. The main burden of CKD is accelerated ageing and premature death. The cut-off points for kidney function and kidney damage indexes that define CKD also mark an increased risk for all-cause premature death. CKD is the most prevalent risk factor for lethal coronavirus disease 2019 (COVID-19) and the factor that most increases the risk of death in COVID-19, after old age. Men and women undergoing KRT still have an annual mortality that is 10- to 100-fold higher than similar-age peers, and life expectancy is shortened by ~40 years for young persons on dialysis and by 15 years for young persons with a functioning kidney graft. CKD is expected to become the fifth greatest global cause of death by 2040 and the second greatest cause of death in Spain before the end of the century, a time when one in four Spaniards will have CKD. However, by 2022, CKD will become the only top-15 global predicted cause of death that is not supported by a dedicated well-funded Centres for Biomedical Research (CIBER) network structure in Spain. Realizing the underestimation of the CKD burden of disease by health authorities, the Decade of the Kidney initiative for 2020-2030 was launched by the American Association of Kidney Patients and the European Kidney Health Alliance. Leading Spanish kidney researchers grouped in the kidney collaborative research network Red de Investigación Renal have now applied for the Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) call for collaborative research in Spain with the support of the Spanish Society of Nephrology, Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true

The Helicobacter pylori Genome Project : insights into H. pylori population structure from analysis of a worldwide collection of complete genomes

Helicobacter pylori, a dominant member of the gastric microbiota, shares co-evolutionary history with humans. This has led to the development of genetically distinct H. pylori subpopulations associated with the geographic origin of the host and with differential gastric disease risk. Here, we provide insights into H. pylori population structure as a part of the Helicobacter pylori Genome Project (HpGP), a multi-disciplinary initiative aimed at elucidating H. pylori pathogenesis and identifying new therapeutic targets. We collected 1011 well-characterized clinical strains from 50 countries and generated high-quality genome sequences. We analysed core genome diversity and population structure of the HpGP dataset and 255 worldwide reference genomes to outline the ancestral contribution to Eurasian, African, and American populations. We found evidence of substantial contribution of population hpNorthAsia and subpopulation hspUral in Northern European H. pylori. The genomes of H. pylori isolated from northern and southern Indigenous Americans differed in that bacteria isolated in northern Indigenous communities were more similar to North Asian H. pylori while the southern had higher relatedness to hpEastAsia. Notably, we also found a highly clonal yet geographically dispersed North American subpopulation, which is negative for the cag pathogenicity island, and present in 7% of sequenced US genomes. We expect the HpGP dataset and the corresponding strains to become a major asset for H. pylori genomics

Search for electroweak production of charginos and neutralinos in multilepton final states in proton-proton collisions at root s=13 TeV

Results are presented from a search for the direct electroweak production of charginos and neutralinos in signatures with either two or more leptons (electrons or muons) of the same electric charge, or with three or more leptons, which can include up to two hadronically decaying tau leptons. The results are based on a sample of protonproton collision data collected at p s = 13TeV, recorded with the CMS detector at the LHC, corresponding to an integrated luminosity of 35.9 fb1. The observed event yields are consistent with the expectations based on the standard model. The results are interpreted in simpli ed models of supersymmetry describing various scenarios for the production and decay of charginos and neutralinos. Depending on the model parameters chosen, mass values between 180GeV and 1150 GeV are excluded at 95% CL. These results signi cantly extend the parameter space probed for these particles in searches at the LHC. In addition, results are presented in a form suitable for alternative theoretical interpretations.Sponsoring Consortium for Open Access Publishing in Particle Physic

Impact of Total Parenteral Nutrition on Gut Microbiota in Pediatric Population Suffering Intestinal Disorders.

Parenteral nutrition (PN) is a life-saving therapy providing nutritional support in patients with digestive tract complications, particularly in preterm neonates due to their gut immaturity during the first postnatal weeks. Despite this, PN can also result in several gastrointestinal complications that are the cause or consequence of gut mucosal atrophy and gut microbiota dysbiosis, which may further aggravate gastrointestinal disorders. Consequently, the use of PN presents many unique challenges, notably in terms of the potential role of the gut microbiota on the functional and clinical outcomes associated with the long-term use of PN. In this review, we synthesize the current evidence on the effects of PN on gut microbiome in infants and children suffering from diverse gastrointestinal diseases, including necrotizing enterocolitis (NEC), short bowel syndrome (SBS) and subsequent intestinal failure, liver disease and inflammatory bowel disease (IBD). Moreover, we discuss the potential use of pre-, pro- and/or synbiotics as promising therapeutic strategies to reduce the risk of severe gastrointestinal disorders and mortality. The findings discussed here highlight the need for more well-designed studies, and harmonize the methods and its interpretation, which are critical to better understand the role of the gut microbiota in PN-related diseases and the development of efficient and personalized approaches based on pro- and/or prebiotics

Solid Dispersions as a Technological Strategy to Improve the Bio-Performance of Antiparasitic Drugs with Limited Solubility

Albendazole (ABZ) and benznidazole (BZL) are drugs with low solubility used in parasitic infections treatment. In this research, solid dispersion (SD) technology was used to enhance ABZ and BZL performance by increasing their dissolution rate and solubility. SDs were prepared by the fusion method, employing Poloxamer 407 (P407) as carrier to disperse 32 of BZL or 50% w/w of ABZ. Furthermore, physical mixtures (PM) of P407 and either ABZ or BZL were also prepared, and then SDs and PMs were characterized. Dissolution tests of SDs, PMs and commercial formulations (CF) of ABZ and BZL were carried out and dissolution profiles were analyzed with the lumped mathematical model, which allowed parameters of pharmaceutical relevance to be obtained. The results indicated that ABZ SD presented an initial dissolution rate (IDR) 21-fold and 11-fold faster than PM and CF, respectively, while the IDR of BZL SD was 2.5-fold and 4.5-fold faster than PM and CF, respectively. For BZL formulations, the time required to reach 80% dissolution of the drug (t80%) was 4 (SD), 46 (PM), and 239 min (CF), while the dissolution efficiency (DE) at 30 min was 85 (DS), 71 (MF) and 65% (FC). For ABZ formulations, t80% was 2 (SD), value not reached (PM) and 40 min (CF), while the DE at 30 min was 85 (SD), 36 (MF) and 65% (CF). The SDs developed notably increased the dissolution rate, in consonance with the values obtained from the pharmaceutical parameters, which could lead to faster absorption and, consequently, increase the bioavailability of these drugs