Food metabolomics applied in cohorts to accelerate the discovery of nutritional biomarkers

communication orale : Claudine ManachThe Second International Congress of Translational Research in Human Nutrition is organised by the Research Centre in Human Nutrition (CRNH) of Auvergne, of which INRA is a member, in collaboration with NuGO, European Association of universities and research institutes in the field of nutrigenomics.The purpose of dietary assessment is to estimate usual and recent intake of foods, nutrients, bioactive compounds and food contaminants for exploration of associations with health outcomes and monitoring of population nutritional status. These data are still extremely difficult to obtain. Methods currently used are based on dietary questionnaires which have inherent limitations linked to self-reporting. A complementary approach to questionnaires is the use of biomarkers. However, only a few biomarkers have been properly validated, which do not cover the wide range offoods consumed. Metabolomics has emerged as a promising approach to discover nutritional biomarkers. Typically, plasma or urine samples collected before and after acute intake of a specific food are profiled using NMR or high resolution Mass Spectrometry (MS) and compared usingmultivariate statistics to pinpoint the signals reflecting the consumption of the target food. In a proof-of-concept study on citrus, we showed that urine profiling of cohort subjects stratified by consumption could be a more effective strategy for discovery of sensitive biomarkers of intake

Use of high resolution mass spectrometry for identification of specific biomarkers of coffee consumption

Présentation poster : Y. FillâtreThe Second International Congress of Translational Research in Human Nutrition is organised by the Research Centre in Human Nutrition (CRNH) of Auvergne, of which INRA is a member, in collaboration with NuGO, European Association of universities and research institutes in the field of nutrigenomicsANR Phenomenep ALIA-2010-007 Conseil Regional Auvergne-FEDER post-doc grantAs part of the ANR PhenoMeNEp project, non-targeted profiling is used to identify potential biomarkers of plant food consumption. Using 24 hour dietary recall and food frequency questionnaire data, 144 high (median 974 grams/day) and 66 low (median 305 grams/day) consumers of fruit and vegetables were selected from the French SU.VI.MAX2 cohort. Morning spot urine samples from each subjec

Nutritional Metabolomics: What are the perspectives?

International audienceUne approche traditionnelle en nutrition a longtemps été d’étudier l’effet d’un régime oubien d’un nutriment donné sur une fonction particulière ou un organe cible, ceci pour expliciter lesmécanismes par lesquels les macro et micronutriments interviennent dans les voies métaboliques. Le développement de techniques analytiques très performantes et d’outils à haut débit comme par exemple la métabolomique ouvre maintenant un champ d’investigation beaucoup plus large permettant d’intégrer un ensemble de réponses biologiques résultant de la complexité de l’aliment et des régimes alimentaires. La métabolomique consiste en l’acquisition à partir de fluides biologiques (sang, urine, salive) de profils métaboliques complexes par l’analyse de centaines de métabolites le plus souvent par 1HRMN, ou différentes techniques de couplage (HPLC-MS ou GC-MS) et leur comparaison par analyses statistiques multivariées. Elle s’est d’abord développée dans le champ de la toxicologie pour prédire les effets toxiques de médicaments dans les phases précoces de développement. Les études en nutritionsont encore récentes mais différents programmes de recherche concernent l’identification de marqueurs précoces de déséquilibres métaboliques associés à l’apparition de pathologies. Deux approches sont possibles: la première est une approche ciblée qui concerne l’étude d’une voie métabolique définie comme par exemple le métabolisme des glucides ou celui des lipides. La deuxième est une approche globale qui consiste à définir une empreinte métabolique en caractérisant le plus grand nombre possible de métabolites afin d’identifier les diverses voies métaboliques perturbées suite au stimuli. Toutefois, les bases de données « métabolites » permettant la saisie et la consultation de molécules identifiées lorsd’explorations nutritionnelles sont encore insuffisantes pour permettre l’identification d’un grand nombre de métabolites. Chez l’homme, il existe également une variabilité interindividuelle importante cequi représente un autre facteur limitant pour cette approche à haut débit. De plus, contrairement aux effets des toxiques, les effets liés à un changement de régime sont souvent de faible amplitude ce quipeut entraîner des difficultés de détection et d’identification des métabolites. La plateforme d’exploration du métabolisme de Clermont-Ferrand participe au développement de l’outil métabolomique dans le domaine de la nutrition et de la bioinformatique en partenariat avec le centre de bioinformatique de Bordeaux (CBiB) en particulier dans le cadre de l’ANR Metaprofile. Il s’agit de structurer une base de données en nutrition incluant non seulement des données de métabolomique mais également des données complémentaires de transcriptomique et de protéomique afin d’interroger et de croiser les différents jeux de données, et ainsi obtenir l’ensemble des informations des gènes aux métabolites

Western Amazonia as a hotspot of mammalian biodiversity throughout the Cenozoic

International audienc

Functional anatomy of the forelimb of Plesiotypotherium achirense (Mammalia, Notoungulata, Mesotheriidae) and evolutionary insights at the family level

International audienceIn the present work, we provide muscular reconstruction and we infer functional properties of the forelimb of Plesiotypotherium achirense, a fossil mesotheriid notoungulate from the late Miocene of Achiri (Bolivia). This locality has yielded the widest sample ever available for the forelimb of a mesotheriid. In addition, we propose a qualitative comparison of the forelimb (osteology and myology) at the family level, including the Miocene–Pleistocene mesotheriines Mesotherium cristatum, Plesiotypotherium achirense, Caraguatypotherium munozi, Plesiotypotherium casirense, and Pseudotypotherium sp, and the late Oligocene trachytheriine Trachytherus alloxus. Functional properties are consistent with a digging ability and a “scratch-digger” lifestyle for Mesotheriidae. In general, there are only slight differences among the comparison sample, except for Mesotherium cristatum, which reflect significant osteological modifications, likely to help increasing the moment arm while scratch-digging. These features are mainly observable on scapulae (distal border caudally displaced) and humeri (deltoid crest distally oriented and crista supracondylaris lateralis laterally projected)

Western Amazonia as a hotspot of mammalian biodiversity throughout the Cenozoic

International audienceA state-of-the-art review of the Cenozoic fossil recordfrom Western Amazonia is provided, based on literatureand new data (regarding Paleogene native ungulates). It allowssummarizing the evolution and dynamics of middleEocene–Holocene mammalian guilds, at the level of species,families, and orders. Major gaps in the Western Amazonianmammal record occur in the pre-Lutetian and early Mioceneintervals, and in the Pliocene epoch. Twenty-three orders, 89families, and 320 species are recognized in the fossil record,widely dominated by eutherians from the middle Eocene onward.Probable Allotheria (Gondwanatheria) occur only in theearliest interval, whereas Metatheria and Eutheria are conspicuouscomponents of any assemblage. Taxonomic diversitywas probably fairly constant at the ordinal level (~12–14 ordersin each time slice considered) and much more variable interms of family and species richness: if most intervals arecharacterized by 40–50 co-occurring species and 19–31 cooccurringfamilies, the early Miocene period illustrates a depauperatefauna (21 species, 17 families), strongly contrastingwith the late Miocene climactic guild (82 species, 38 families).Recent mammalian taxonomic diversity from WesternAmazonia (12 orders, 37 families, and 286 species) is at oddswith all past intervals, as it encompasses only three orders ofSouth American origin (Didelphimorphia, Cingulata, andPilosa) but four North American immigrant orders(Artiodactyla, Perissodactyla, Carnivora, and Lagomorpha).In terms of taxonomic diversity, recent mammalian guildsare fully dominated by small-sized taxa (Chiroptera,Rodentia, and Primates). This overview also confirms thescarcity of large mammalian flesh-eaters in ancientNeotropical mammalian assemblages. The pattern and thetiming of mammalian dispersals from northern landmassesinto Western Amazonia are not elucidated yet

Development and validation of a UPLC/MS method for a nutritional metabolomic study of human plasma

International audienceIn order to study the effect of a diet on metabolites found in body fluids such as plasma, we have developed and validated a UPLC/MS method. While methods using NMR have been well established to analyse different biological tissues, recent studies have described robust untargeted UPLC-MS methods for plasma analysis. One major concern when profiling plasma is the presence of an important quantity of proteins which have to be precipitated without any loss of metabolites prior to LC/MS analysis. The utilization of untargeted approaches in nutritional metabolomics still suffers from the lack of identification of specific biomarkers. We therefore suggest an alternative method still using a global approach but focusing at the same time on metabolites previously described in human plasma in order to detect biomarkers of metabolic dysregulations. Thus, to fulfil our objectives, analytical parameters were tested (i) the anticoagulant type for sample collection, (ii) the protein precipitation method and (iii) UPLC/MS analytical conditions. Three protein precipitation methods and two anticoagulants were tested and compared. The method utilizing blood collection on heparin and methanol precipitation was chosen for giving the most reproducible results while keeping the complexity of the sample. Finally, a validation was proposed to evaluate the stability of this analytical method applied to a large batch of samples for nutritional metabolomic studies

Un inventaire fossile de la Guyane : historique et nouvelles perspectives

International audienc

Evolution of body size in anteaters and sloths (Xenarthra, Pilosa): phylogeny, metabolism, diet and substrate preferences

Fil: Toledo, Néstor. División Paleontología Vertebrados. Facultad de Ciencias Naturales y Museo. Universidad Nacional de La Plata; ArgentinaFil: Bargo, María Susana. División Paleontología Vertebrados. Facultad de Ciencias Naturales y Museo. Universidad Nacional de La Plata; ArgentinaFil: Vizcaíno, Sergio Fabián. División Paleontología Vertebrados. Facultad de Ciencias Naturales y Museo. Universidad Nacional de La Plata; ArgentinaFil: De Iuliis, Gerardo. Department of Ecology and Evolutionary Biology. University of Toronto; CanadaFil: Pujos, Francois. IANIGLA. Mendoza. Mendoza; Argentin

The utilization of sulfur amino acid in the mercapturate pathway to detoxify maximal therapeutic dose of acetaminophen is associated with glutathione and protein homeosteny in adult rats

International audienc