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)

A Complex mHealth Coaching Intervention to Prevent Overweight, Obesity, and Diabetes in High-Risk Women in Antenatal Care: Protocol for a Hybrid Type 2 Effectiveness-Implementation Study

This project is funded by the European Union Commission Horizon 2020 grant entitled "Implementation Action to Prevent Diabetes from Bump 2 Baby (IMPACT DIABETES B2B) " under grant agreement 847984, with collaborative National Health and Medical Research Council, Australia co -funding under grant number APP1194234. The project is sponsored by University College Dublin. The funders and the sponsor have no role in the design of the study, the collection, analysis, and interpretation of data, or in the writing of the manuscript or decision to publish. The contributors associated with IMPACT DIABETES B2B Consortium1 are as follows: Janine Wirth, School of Agriculture and Food Science, University College Dublin, Dublin, Ireland; Mary Codd, School of Public Health, Physiotherapy and Sports Science, University College Dublin, Dublin, Ireland; Ricardo Segurado, School of Public Health, Physiotherapy and Sports Science, University College Dublin, Dublin, Ireland; Jacqueline Boyle, Eastern Health Clinical School, Monash University, Melbourne, Australia; Georgia Soldartis, Monash Health, Melbourne, Australia; Alberto Puertas, School of Medicine, University of Granada, Granada, Spain; Francisca S Molina, School of Medicine, University of Granada, Granada, Spain; Maria Garcia-Ricobaraza, School of Medicine, University of Granada, Granada, Spain; Nanna Husted Jensen, Department of Public Health, Aarhus University, Aarhus, Denmarkv; Elena Rey Velasco, Liva Healthcare, Copenhagen, Denmark.Background: Women with overweight and obesity are at higher risk of developing complications in pregnancy such as gestational diabetes and longer-term chronic conditions. Research concerning health behavior change interventions during pregnancy and postpartum shows promising effects, but implementation into routine services is sparsely investigated. Most interventions focus on the antenatal or postpartum life stages, failing to meet the needs of women. IMPACT DIABETES Bump2Baby is a multicenter project across 4 high-income countries developed to test the implementation of an antenatal and postpartum evidence-based mobile health (mHealth) coaching intervention called Bump2Baby and Me (B2B&Me) designed to sit alongside usual care in the perinatal period. Objective: We aim to explore the feasibility and implementation of the B2B&Me intervention and investigate the effectiveness of this intervention in women at risk of gestational diabetes. Methods: IMPACT DIABETES Bump2Baby is a hybrid type 2 effectiveness-implementation study, which integrates an evidence-based mHealth coaching app that includes personalized health behavior change coaching provided by health care professionals alongside antenatal care from the first antenatal visit to 12 months postpartum. The mHealth app offers the possibility of synchronous calls, asynchronous contact (including coach-participant text and video messaging exchanges tailored to the participant’s needs), and ongoing access to an extensive library of bespoke intervention materials. Participants will interact asynchronously with their health coach throughout the intervention via the app. This randomized controlled trial across 4 clinical sites within Ireland, the United Kingdom, Spain, and Australia will recruit 800 women in early pregnancy to evaluate the effectiveness on postpartum weight. The Exploration, Preparation, Implementation, and Sustainment implementation framework is the theoretical underpinning of the study. The implementation evaluation will be assessed at the individual, hospital staff, and broader community levels using the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework. Data sources for the RE-AIM evaluation will include app and platform analytics, screening and training records, participant medical records, key informant interviews, participant and partner exit interviews, cost data, study questionnaires, staff surveys, and blood sample analyses. Results: The study was approved and registered with the Australian New Zealand Clinical Trials Registry on November 19, 2020. Recruitment commenced on February 9, 2021, and data collection is ongoing. Publication of the results is expected in 2024. Conclusions: This is the first hybrid effectiveness-implementation study of an 18-month mHealth coaching intervention in at-risk women that we are aware of. As research aims to move toward real-world implementable solutions, it is critical that hybrid studies are conducted. The data from this large multicenter study will be useful in planning the potential implementation and scale-up of evidence-based perinatal health behavior change interventions.Horizon 2020 847984National Health and Medical Research Council (NHMRC) of Australia APP119423

Maternal weight, gut microbiota, and the association with early childhood behavior: the PREOBE follow-up study

Background and aim Maternal overweight and breastfeeding seem to have a significant impact on the gut microbiota colonization process, which co-occurs simultaneously with brain development and the establishment of the “microbiota-gut-brain axis”, which potentially may affect behavior later in life. This study aimed to examine the influence of maternal overweight, obesity and/or gestational diabetes on the offspring behavior at 3.5 years of age and its association with the gut microbiota already established at 18 months of life. Methods 156 children born to overweight (OV, n = 45), obese (OB, n = 40) and normoweight (NW, n = 71) pregnant women participating in the PREOBE study were included in the current analysis. Stool samples were collected at 18 months of life and gut microbiome was obtained by 16S rRNA gene sequencing. Behavioral problems were evaluated at 3.5 years by using the Child Behavior Checklist (CBCL). ANOVA, Chi-Square Test, ANCOVA, Spearman’s correlation, logistic regression model and generalized linear model (GLM) were performed. Results At 3.5 years of age, Children born to OV/OB mothers showed higher scores in behavioral problems than those born to NW mothers. Additionally, offspring born to OB mothers who developed gestational diabetes mellitus (GDM) presented higher scores in attention/deficit hyperactivity and externalizing problems than those born to GDM OV/NW mothers. Fusicatenibacter abundance found at 18 months of age was associated to lower scores in total, internalizing and pervasive developmental problems, while an unidentified genus within Clostridiales and Flavonifractor families abundance showed a positive correlation with anxiety/depression and somatic complaints, respectively. On the other hand, children born to mothers with higher BMI who were breastfed presented elevated anxiety, internalizing problems, externalizing problems and total problems scores; likewise, their gut microbiota composition at 18 months of age showed positive correlation with behavioral problems at 3.5 years: Actinobacteria abundance and somatic complaints and between Fusobacteria abundance and withdrawn behavior and pervasive developmental problems. Conclusions Our findings suggests that OV/OB and/or GDM during pregnancy is associated with higher behavioral problems scores in children at 3.5 years old. Additionally, associations between early life gut microbiota composition and later mental health in children was also found.Andalusian Government, Economy, Science and Innovation Ministry P06-CTS-02341Spanish Government SB2010-0025EU Project FP7 MyNewGut KBBE-2013-7 613979Ministry of Economic Transformation, Industry, Knowledge, and University of the Junta de Andalucia (Andalusian Plan for Research, Development and Innovation, PAIDI 2020)Institute of Health Carlos III (ISCIII) CD21/0018

Association study between hypothalamic functional connectivity, early nutrition, and glucose levels in healthy children aged 6 years: The COGNIS study follow-up

Breastfeeding (BF) is the gold standard in infant nutrition; knowing how it influences brain connectivity would help understand the mechanisms involved, which would help close the nutritional gap between infant formulas and breast milk. We analyzed potential long-term differences depending on the diet with an experimental infant formula (EF), compared to a standard infant formula (SF) or breastfeeding (BF) during the first 18 months of life on children's hypothalamic functional connectivity (FC) assessed at 6 years old. A total of 62 children participating in the COGNIS randomized clinical trial (Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02094547) were included in this study. They were randomized to receive an SF (n = 22) or a bioactive nutrient-enriched EF (n = 20). BF children were also included as a control study group (BF: n = 20). Brain function was evaluated using functional magnetic resonance imaging (fMRI) and mean glucose levels were collected through a 24-h continuous glucose monitoring (CGM) device at 6 years old. Furthermore, nutrient intake was also analyzed during the first 18 months of life and at 6 years old through 3-day dietary intake records. Groups fed with EF and BF showed lower FC between the medial hypothalamus (MH) and the anterior cingulate cortex (ACC) in comparison with SF-fed children. Moreover, the BF children group showed lower FC between the MH and the left putamen extending to the middle insula, and higher FC between the MH and the inferior frontal gyrus (IFG) compared to the EF-fed children group. These areas are key regions within the salience network, which is involved in processing salience stimuli, eating motivation, and hedonic-driven desire to consume food. Indeed, current higher connectivity found on the MH-IFG network in the BF group was associated with lower simple sugars acceptable macronutrient distribution ranges (AMDRs) at 6 months of age. Regarding linoleic acid intake at 12 months old, a negative association with this network (MH-IFG) only in the BF group was found. In addition, BF children showed lower mean glucose levels compared to SF-fed children at 6 years old. Our results may point out a possible relationship between diet during the first 18 months of life and inclined proclivity for hedonic eating later in life.Randox LaboratoriesS.L. Contract University of Granada General FoundationSpanish Government 3349Contract University of Granada General Foundation 3349European Commission CIEN-IDI-20141206Junta de Andalucia Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades 4003Fundacion Carolina, Madrid, Spain 633595 40

Acompañamiento directo para la mejora de la práctica docente en la unidad educativa Albertina Rivas Medina

The managerial accompaniment for the improvement of teaching practice is important in the educational field because it allows improvements to be achieved to be able to implement in teaching praxis and in that sense the educational institution can achieve new skills complying with what is indicated by the Ministry of Education of the Ecuador in educational standards. The objective of the research was to develop an intervention proposal for the managerial accompaniment process that strengthens the pedagogical practice of teachers in the Albertina Rivas Medina Educational Unit. The study was carried out under a mixed approach, theoretical, empirical and statistical methods were applied. The study was carried out at the Albertina Rivas Medina Educational Unit at the Baccalaureate level, a structured base survey was applied to teachers and an interview with the directors of the institution. The results detect that teachers need to increase their knowledge in the domain of didactic and methodological strategies so that they have good classroom practices, this is evidenced in the applied evaluations where the results indicate that they do not meet the educational standards of Ecuador. It is concluded that the managerial accompaniment for the improvement of the teaching practice is important to detect the problems in the process inherent to the educational institution, proposing improvements in them, reaching high scores in the evaluations carried out by the pedagogical advisors.El acompañamiento directivo para la mejora de la práctica docente es importante en el ámbito educativo porque permite que se logren mejoras para poder implementar en la praxis y en este sentido la institución educativa pueda alcanzar nuevas habilidades cumpliendo con lo que indica el Ministerio de Educación del Ecuador en los estándares educativos. El objetivo de la investigación fue elaborar una propuesta de intervención para el proceso de acompañamiento directivo que fortalezca la práctica pedagógica de los docentes en la Unidad Educativa Albertina Rivas Medina. El estudio se realizó bajo un enfoque mixto, se aplicaron los métodos teóricos, empíricos y estadístico. El estudio se realizó en la Unidad Educativa Albertina Rivas Medina en el nivel de Bachillerato, se aplicó una encuesta de base estructurada a los docentes y una entrevista a los directivos de la institución. Los resultados detectan que los docentes necesitan incrementar sus conocimientos en el dominio de estrategias didácticas y metodológicas para que tengan buenas prácticas de aula, esto evidenciado en las evaluaciones aplicadas en donde los resultados indican que no cumplen con los estándares educativos del Ecuador. Se concluye que el acompañamiento directivo para la mejora de la práctica docente es importante para detectar las problemáticas en el proceso inherentes a la institución educativa proponiendo mejoras en ellos alcanzando altos puntajes en las evaluaciones que realizan los asesores pedagógicos. &nbsp

Association study of rs1801282 PPARG gene polymorphism and immune cells and cytokine levels in a Spanish pregnant women cohort and their offspring

Background: Peroxisome proliferator activated receptor gamma (PPARG ) belongs to the nuclear receptor superfamily functioning as transcription factors to regulate cellular differentiation, development and metabolism. Moreover, it has been implicated in the regulation of lipid metabolism, as well as the maturation of monocytes/macrophages and the control of inflammatory reactions. The aim of this study was to evaluate the relationship between the Pro12Ala (rs1808212) PPARG gene polymorphism on immune molecular and cellular components in mothers and their offspring participating in the PREOBE study. Methods: DNA from maternal venous blood samples at 24, 34 and 40 gestational weeks, plus cord blood samples was extracted. Pro12Ala PPARG polymorphism genotyping was performed, and immune system markers were analyzed by flow cytometry. Results: Study findings revealed no effect of rs1808212 PPARG genotypes on innate immune parameters in mothers and their offspring; however, CD4 + /CD8 + ratio were decreased at 24 and 34 weeks in pregnant women carrying the CG (Pro12Ala) rs1808212 polymorphism, (p = 0,012 and p = 0,030; respectively). Only CD19 levels in peripheral blood were significantly higher at delivery in pregnant women carrying the CC (Pro12Pro) genotype (p ≤ 0.001). Moreover, there were statistically significant differences in leukocytes and neutrophils maternal levels at 34 weeks of gestation, being lower in carriers of Pro12Ala genotype (p = 0.028 and p = 0.031, respectively). Conclusions: Results suggest that Pro12Ala PPARG polymorphism may have an effect on some cell and immune parameters in pregnant women during pregnancy and at time of delivery. However, newborn innate immune system does not seems to be influenced by PPARG Pro12Ala polymorphism in cord blood.Andalusian Ministry of Innovation and Science, Junta de Andalucía, Excellence Project P06-CTS-02341Spanish Ministry of Economy and Competitiveness BFU2012-40254-C03-01Abbott Laboratories, Granada, Spai

The mRNA degradation factor Xrn1 regulates transcription elongation in parallel to Ccr4

Co-transcriptional imprinting of mRNA by Rpb4 and Rpb7 subunits of RNA polymerase II (RNAPII) and by the Ccr4–Not complex conditions its posttranscriptional fate. In turn, mRNA degradation factors like Xrn1 are able to influence RNAPII-dependent transcription, making a feedback loop that contributes to mRNA homeostasis. In this work, we have used repressible yeast GAL genes to perform accurate measurements of transcription and mRNA degradation in a set of mutants. This genetic analysis uncovered a link from mRNA decay to transcription elongation. We combined this experimental approach with computational multi-agent modelling and tested different possibilities of Xrn1 and Ccr4 action in gene transcription. This double strategy brought us to conclude that both Xrn1-decaysome and Ccr4–Not regulate RNAPII elongation, and that they do it in parallel. We validated this conclusion measuring TFIIS genome-wide recruitment to elongating RNAPII. We found that xrn1Δ and ccr4Δ exhibited very different patterns of TFIIS versus RNAPII occupancy, which confirmed their distinct role in controlling transcription elongation. We also found that the relative influence of Xrn1 and Ccr4 is different in the genes encoding ribosomal proteins as compared to the rest of the genome

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

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).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.Laboratorios OrdesaContract University of Granada General Foundation 3349SMARTFOODS (CIEN) Contract University of Granada General Foundation 4003Spanish Ministry of Economy, Industry and Competitiveness. FurthermoreEU DynaHEALTH Project 63359

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)

The Effects of an Infant Formula Enriched with Milk Fat Globule Membrane, Long-Chain Polyunsaturated Fatty Acids and Synbiotics on Child Behavior up to 2.5 Years Old: The COGNIS Study

Although early life nutrition influences brain development and mental health, the long-term e ects of supplemented infant formula on children´s behavior remain unclear. We analyzed the e ects of a bioactive nutrients-enriched-infant formula on children’s behavior up to 2.5 years, compared to a standard infant formula or breastfeeding. Current analysis involved 70 children who were fed a standard infant formula (SF, n = 29) or a bioactive compounds enriched-infant formula (EF, n = 41), during their first 18 months of life, and 33 breastfed (BF) children (reference group) participating in the COGNIS study. Behavioral problems were evaluated using the Child Behavior Checklist at 18 months and 2.5 years. Di erent statistical analyses were performed using SPSS. EF children aged 2.5 years presented fewer pathological a ective problems than SF children. Besides, SF children were classified more frequently as bordering on internalizing problems than BF children. Rates of externalizing problems were increased in SF infants compared to EF and BF infants. Higher maternal IQ was found to have beneficial e ects on internalizing and total problem rate in their o spring at 18 months of life; finally, higher maternal educational level was related with fewer ADHD problems in children at 18 months, as well as internalizing, externalizing, total and anxiety problems in children aged 2.5 years. Our analysis suggests that enriched infant formula fed infants seem to show fewer behavioral problems up to 2.5 years compared to a standard infant formula-fed infants. In addition to type of early feeding, maternal IQ and educational level seem to play a key role on children behavioral development.Ordesa LaboratoriesS.L. Contract University of Granada General Foundation 3349SMARTFOODS (CIEN) Contract University of Granada General Foundation 4003Spanish Ministry of Economy, Industry and CompetitivenessHORIZON 2020 EU DynaHEALTH Project 633595Fundación Carolina, Madrid, SpainCatedra ORDESA-University of Granada, Spain as part of Special Issue "Early Nutrition and Re-programming of Health and Disease