Nutrimetabolomics: An Integrative Action for Metabolomic Analyses in Human Nutritional Studies

The life sciences are currently being transformed by an unprecedented wave of developments in molecular analysis, which include important advances in instrumental analysis as well as biocomputing. In light of the central role played by metabolism in nutrition, metabolomics is rapidly being established as a key analytical tool in human nutritional studies. Consequently, an increasing number of nutritionists integrate metabolomics into their study designs. Within this dynamic landscape, the potential of nutritional metabolomics (nutrimetabolomics) to be translated into a science, which can impact on health policies, still needs to be realized. A key element to reach this goal is the ability of the research community to join, to collectively make the best use of the potential offered by nutritional metabolomics. This article, therefore, provides a methodological description of nutritional metabolomics that reflects on the state‐of‐the‐art techniques used in the laboratories of the Food Biomarker Alliance (funded by the European Joint Programming Initiative "A Healthy Diet for a Healthy Life" (JPI HDHL)) as well as points of reflections to harmonize this field. It is not intended to be exhaustive but rather to present a pragmatic guidance on metabolomic methodologies, providing readers with useful "tips and tricks" along the analytical workflow

Genetic landscape of a large cohort of Primary Ovarian Insufficiency : New genes and pathways and implications for personalized medicine

Background Primary Ovarian Insufficiency (POI), a public health problem, affects 1-3.7% of women under 40 yield-ing infertility and a shorter lifespan. Most causes are unknown. Recently, genetic causes were identified, mostly in single families. We studied an unprecedented large cohort of POI to unravel its molecular pathophysiology.Methods 375 patients with 70 families were studied using targeted (88 genes) or whole exome sequencing with pathogenic/likely-pathogenic variant selection. Mitomycin-induced chromosome breakages were studied in patients' lymphocytes if necessary. Findings A high-yield of 29.3% supports a clinical genetic diagnosis of POI. In addition, we found strong evidence of pathogenicity for nine genes not previously related to a Mendelian phenotype or POI: ELAVL2, NLRP11, CENPE, SPATA33, CCDC150, CCDC185, including DNA repair genes: C17orf53(HROB), HELQ, SWI5 yielding high chromo-somal fragility. We confirmed the causal role of BRCA2, FANCM, BNC1, ERCC6, MSH4, BMPR1A, BMPR1B, BMPR2, ESR2, CAV1, SPIDR, RCBTB1 and ATG7 previously reported in isolated patients/families. In 8.5% of cases, POI is the only symptom of a multi-organ genetic disease. New pathways were identified: NF-kB, post-translational regulation, and mitophagy (mitochondrial autophagy), providing future therapeutic targets. Three new genes have been shown to affect the age of natural menopause supporting a genetic link.Interpretation We have developed high-performance genetic diagnostic of POI, dissecting the molecular pathogene-sis of POI and enabling personalized medicine to i) prevent/cure comorbidities for tumour/cancer susceptibility genes that could affect life-expectancy (37.4% of cases), or for genetically-revealed syndromic POI (8.5% of cases), ii) predict residual ovarian reserve (60.5% of cases). Genetic diagnosis could help to identify patients who may benefit from the promising in vitro activation-IVA technique in the near future, greatly improving its success in treating infertility.Funding Universite? Paris Saclay, Agence Nationale de Biome?decine.Copyright (c) 2022 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)Peer reviewe

Symptom-based stratification of patients with primary Sjögren's syndrome: multi-dimensional characterisation of international observational cohorts and reanalyses of randomised clinical trials

Background Heterogeneity is a major obstacle to developing effective treatments for patients with primary Sjögren's syndrome. We aimed to develop a robust method for stratification, exploiting heterogeneity in patient-reported symptoms, and to relate these differences to pathobiology and therapeutic response. Methods We did hierarchical cluster analysis using five common symptoms associated with primary Sjögren's syndrome (pain, fatigue, dryness, anxiety, and depression), followed by multinomial logistic regression to identify subgroups in the UK Primary Sjögren's Syndrome Registry (UKPSSR). We assessed clinical and biological differences between these subgroups, including transcriptional differences in peripheral blood. Patients from two independent validation cohorts in Norway and France were used to confirm patient stratification. Data from two phase 3 clinical trials were similarly stratified to assess the differences between subgroups in treatment response to hydroxychloroquine and rituximab. Findings In the UKPSSR cohort (n=608), we identified four subgroups: Low symptom burden (LSB), high symptom burden (HSB), dryness dominant with fatigue (DDF), and pain dominant with fatigue (PDF). Significant differences in peripheral blood lymphocyte counts, anti-SSA and anti-SSB antibody positivity, as well as serum IgG, κ-free light chain, β2-microglobulin, and CXCL13 concentrations were observed between these subgroups, along with differentially expressed transcriptomic modules in peripheral blood. Similar findings were observed in the independent validation cohorts (n=396). Reanalysis of trial data stratifying patients into these subgroups suggested a treatment effect with hydroxychloroquine in the HSB subgroup and with rituximab in the DDF subgroup compared with placebo. Interpretation Stratification on the basis of patient-reported symptoms of patients with primary Sjögren's syndrome revealed distinct pathobiological endotypes with distinct responses to immunomodulatory treatments. Our data have important implications for clinical management, trial design, and therapeutic development. Similar stratification approaches might be useful for patients with other chronic immune-mediated diseases. Funding UK Medical Research Council, British Sjogren's Syndrome Association, French Ministry of Health, Arthritis Research UK, Foundation for Research in Rheumatology

GAME 2014

GAME - Global Approach by Modular Experiments is in an international training programme that combines applied research with training for young scientists. Every year, parallel research projects on current ecological issues are organised at different locations around the world. The research is carried out by students working in bi-national pairs and supervised by scientists from GAME’s partner institutes. The unique GAME projects enable generalizable insights into urgent ecological issues. At the same time GAME links GEOMAR with numerous partner institutes worldwide and creates a global network for the sustainable exchange of scientific knowledge. In 2014, the participants investigate if microplastic is able to harm marine animals. In a short film, they report about their life and work

La contribución de la producción del cacao orgánico a la resiliencia socio-ecológica en el contexto del cambio climático en el Alto Beni – La Paz

El cultivo del cacao en pequeña escala, sustento básico de muchas familias del Alto Beni, es afectado por los impactos del cambio climático. Para el desarrollo sostenible, es necesario que las fincas adquieran resiliencia: la capacidad de un sistema para reducir su sensibilidad hacia factores de estrés y perturbaciones, manteniendo su productividad, capacidad auto-organizativa, de aprendizaje y adaptación al cambio. Investigamos las diferencias en la resiliencia entre las fincas orgánicas y no orgánicas de cacao, y los rasgos significativos que inciden en la resiliencia socio-ecológica de los sistemas agrícolas del cacao. Definimos indicadores de resiliencia con expertos locales y productores durante un taller y con grupos focales. Los indicadores de la capacidad de amortiguación fueron: materia orgánica de los suelos, densidad aparente del suelo, e infestación con Moniliophthora perniciosa, diversidad arbórea, diversidad de cultivos, hormigas y fuentes de ingresos de las familias productoras. Los indicadores de auto-organización fueron: afiliación a organizaciones productoras, nivel de subsistencia, rendimientos de cacao e ingreso familiar anual. La capacidad de adaptación se evaluó indagando la cantidad de capacitaciones en que participaron las familias y la cantidad de fuentes de información que poseían. Entrevistamos 52 hogares: 30 orgánicos, 22 no orgánicos. Las fincas orgánicas en el área eran más diversificadas y rendían más. El ingreso familiar anual de las fincas orgánicas era sustancialmente mayor al de las no orgánicas. Probablemente el mayor rendimiento se debió principalmente a que los productores orgánicos participaron en más capacitaciones debido a su pertenencia a las organizaciones locales. Concluimos que las organizaciones locales de agricultura orgánica contribuyeron a crear resiliencia proporcionando servicios de extensión mediante el establecimiento de parcelas, creación de capacidades y seguros sociale

Farm resilience in organic and nonorganic cocoa farming systems in Alto Beni, Bolivia

Cocoa production in Alto Beni, Bolivia, is a major source of income and is severely affected by climate change impacts and other stress factors. Resilient farming systems are, thus, important for local families. This study compares indicators for social–ecological resilience in 30 organic and 22 nonorganic cocoa farms of Alto Beni. Organic farms had a higher tree and crop diversity, higher yields and incomes, more social connectedness, and participated in more courses on cocoa cultivation. Resilience was enhanced by local farmers’ organizations, providing organic certification and supporting diversified agroforestry with seedlings and extension, going beyond basic organic certification requirements

Image3_Acute effects of moderate vs. vigorous endurance exercise on urinary metabolites in healthy, young, physically active men—A multi-platform metabolomics approach.JPEG

Introduction: Endurance exercise alters whole-body as well as skeletal muscle metabolism and physiology, leading to improvements in performance and health. However, biological mechanisms underlying the body’s adaptations to different endurance exercise protocols are not entirely understood.Methods: We applied a multi-platform metabolomics approach to identify urinary metabolites and associated metabolic pathways that distinguish the acute metabolic response to two endurance exercise interventions at distinct intensities. In our randomized crossover study, 16 healthy, young, and physically active men performed 30 min of continuous moderate exercise (CME) and continuous vigorous exercise (CVE). Urine was collected during three post-exercise sampling phases (U01/U02/U03: until 45/105/195 min post-exercise), providing detailed temporal information on the response of the urinary metabolome to CME and CVE. Also, fasting spot urine samples were collected pre-exercise (U00) and on the following day (U04). While untargeted two-dimensional gas chromatography-mass spectrometry (GC×GC-MS) led to the detection of 608 spectral features, 44 metabolites were identified and quantified by targeted nuclear magnetic resonance (NMR) spectroscopy or liquid chromatography-mass spectrometry (LC-MS).Results: 104 urinary metabolites showed at least one significant difference for selected comparisons of sampling time points within or between exercise trials as well as a relevant median fold change >1.5 or 2.0 or Discussion: To conclude, this study provided first evidence of specific urinary metabolites as potential metabolic markers of endurance exercise intensity. Future studies are needed to validate our results and to examine whether acute metabolite changes in urine might also be partly reflective of mechanisms underlying the health- or performance-enhancing effects of endurance exercise, particularly if performed at high intensities.</p