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98 results on '"Cécile Canlet"'

1. Pharmacological activation of constitutive androstane receptor induces female-specific modulation of hepatic metabolism

Author: Marine Huillet, Frédéric Lasserre, Marie-Pierre Gratacap, Beatrice Engelmann, Justine Bruse, Arnaud Polizzi, Tiffany Fougeray, Céline Marie Pauline Martin, Clémence Rives, Anne Fougerat, Claire Naylies, Yannick Lippi, Géraldine Garcia, Elodie Rousseau-Bacquie, Cécile Canlet, Laurent Debrauwer, Ulrike Rolle-Kampczyk, Martin von Bergen, Bernard Payrastre, Elisa Boutet-Robinet, Laurence Gamet-Payrastre, Hervé Guillou, Nicolas Loiseau, and Sandrine Ellero-Simatos
Subjects: Sexual dimorphism, Hepatic xenobiotic metabolism, Lipoprotein metabolism, Platelet aggregation, Trimethylamine-N-oxide, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Background & Aims: The constitutive androstane receptor (CAR) is a nuclear receptor that binds diverse xenobiotics and whose activation leads to the modulation of the expression of target genes involved in xenobiotic detoxification and energy metabolism. Although CAR hepatic activity is considered to be higher in women than in men, its sex-dependent response to an acute pharmacological activation has seldom been investigated. Methods: The hepatic transcriptome, plasma markers, and hepatic metabolome, were analysed in Car+/+ and Car-/- male and female mice treated either with the CAR-specific agonist 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) or with vehicle. Results: Although 90% of TCPOBOP-sensitive genes were modulated in a sex-independent manner, the remaining 10% showed almost exclusive female liver specificity. These female-specific CAR-sensitive genes were mainly involved in xenobiotic metabolism, inflammation, and extracellular matrix organisation. CAR activation also induced higher hepatic oxidative stress and hepatocyte cytolysis in females than in males. Hepatic expression of flavin monooxygenase 3 (Fmo3) was almost abolished and was associated with a decrease in hepatic trimethylamine-N-oxide (TMAO) concentration in TCPOBOP-treated females. In line with a potential role in the control of TMAO homeostasis, CAR activation decreased platelet hyper-responsiveness in female mice supplemented with dietary choline. Conclusions: More than 10% of CAR-sensitive genes are sex-specific and influence hepatic and systemic responses such as platelet aggregation. CAR activation may be an important mechanism of sexually-dimorphic drug-induced liver injury. Impact and implications: CAR is activated by many drugs and pollutants. Its pharmacological activation had a stronger impact on hepatic gene expression and metabolism in females than in males, and had a specific impact on liver toxicity and trimethylamine metabolism. Sexual dimorphism should be considered when testing and/or prescribing xenobiotics known to activate CAR.
Published: 2024
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2. Lactobacillus supports Clostridiales to restrict gut colonization by multidrug-resistant Enterobacteriaceae

Author: Ana Djukovic, María José Garzón, Cécile Canlet, Vitor Cabral, Rym Lalaoui, Marc García-Garcerá, Julia Rechenberger, Marie Tremblay-Franco, Iván Peñaranda, Leonor Puchades-Carrasco, Antonio Pineda-Lucena, Eva María González-Barberá, Miguel Salavert, José Luis López-Hontangas, Miguel Á. Sanz, Jaime Sanz, Bernhard Kuster, Jean-Marc Rolain, Laurent Debrauwer, Karina B. Xavier, Joao B. Xavier, and Carles Ubeda
Subjects: Science
Abstract: Multidrug-resistant Enterobacteriaceae (MRE) represent a major threat for patients’ health. Here, the authors describe how cooperation between gut commensal bacteria (Lactobacillus spp. And Clostridiales) restrict MRE colonization in mice and patients
Published: 2022
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3. Chronic dietary exposure to a glyphosate-based herbicide results in total or partial reversibility of plasma oxidative stress, cecal microbiota abundance and short-chain fatty acid composition in broiler hens

Author: Mathias Fréville, Anthony Estienne, Christelle Ramé, Gaëlle Lefort, Marine Chahnamian, Christophe Staub, Eric Venturi, Julie Lemarchand, Elise Maximin, Alice Hondelatte, Olivier Zemb, Cécile Canlet, Rodrigo Guabiraba, Pascal Froment, and Joëlle Dupont
Subjects: birds, glyphosate, metabolism, cecal microbiome, oxidative stress, Physiology, QP1-981
Abstract: Glyphosate-based herbicides (GBHs) are massively used in agriculture. However, few studies have investigated the effects of glyphosate-based herbicides on avian species although they are largely exposed via their food. Here, we investigated the potential reversibility of the effects of chronic dietary exposure to glyphosate-based herbicides in broiler hens. For 42 days, we exposed 32-week-old hens to glyphosate-based herbicides via their food (47 mg/kg/day glyphosate equivalent, glyphosate-based herbicides, n = 75) corresponding to half glyphosate’s no-observed-adverse-effect-level in birds. We compared their performance to that of 75 control animals (CT). Both groups (glyphosate-based herbicides and control animals) were then fed for 28 additional days without glyphosate-based herbicides exposure (Ex-glyphosate-based herbicides and Ex-control animals). Glyphosate-based herbicides temporarily increased the plasma glyphosate and AMPA (aminomethylphosphonic acid) concentrations. Glyphosate and aminomethylphosphonic acid mostly accumulated in the liver and to a lesser extent in the leg muscle and abdominal adipose tissue. Glyphosate-based herbicides also temporarily increased the gizzard weight and plasma oxidative stress monitored by TBARS (thiobarbituric acid reactive substances). Glyphosate-based herbicides temporarily decreased the cecal concentrations of propionate, isobutyrate and propionate but acetate and valerate were durably reduced. The cecal microbiome was also durably affected since glyphosate-based herbicides inhibited Barnesiella and favored Alloprevotella. Body weight, fattening, food intake and feeding behavior as well as plasma lipid and uric acid were unaffected by glyphosate-based herbicides. Taken together, our results show possible disturbances of the cecal microbiota associated with plasma oxidative stress and accumulation of glyphosate in metabolic tissues in response to dietary glyphosate-based herbicides exposure in broiler hens. Luckily, glyphosate-based herbicides at this concentration does not hamper growth and most of the effects on the phenotypes are reversible.
Published: 2022
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4. Integrative biology defines novel biomarkers of resistance to strongylid infection in horses

Author: Guillaume Sallé, Cécile Canlet, Jacques Cortet, Christine Koch, Joshua Malsa, Fabrice Reigner, Mickaël Riou, Noémie Perrot, Alexandra Blanchard, and Núria Mach
Subjects: Medicine, Science
Abstract: Abstract The widespread failure of anthelmintic drugs against nematodes of veterinary interest requires novel control strategies. Selective treatment of the most susceptible individuals could reduce drug selection pressure but requires appropriate biomarkers of the intrinsic susceptibility potential. To date, this has been missing in livestock species. Here, we selected Welsh ponies with divergent intrinsic susceptibility (measured by their egg excretion levels) to cyathostomin infection and found that their divergence was sustained across a 10-year time window. Using this unique set of individuals, we monitored variations in their blood cell populations, plasma metabolites and faecal microbiota over a grazing season to isolate core differences between their respective responses under worm-free or natural infection conditions. Our analyses identified the concomitant rise in plasma phenylalanine level and faecal Prevotella abundance and the reduction in circulating monocyte counts as biomarkers of the need for drug treatment (egg excretion above 200 eggs/g). This biological signal was replicated in other independent populations. We also unravelled an immunometabolic network encompassing plasma beta-hydroxybutyrate level, short-chain fatty acid producing bacteria and circulating neutrophils that forms the discriminant baseline between susceptible and resistant individuals. Altogether our observations open new perspectives on the susceptibility of equids to strongylid infection and leave scope for both new biomarkers of infection and nutritional intervention.
Published: 2021
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5. Gestational exposure to bisphenol A induces region-specific changes in brain metabolomic fingerprints in sheep

Author: Davy Guignard, Cécile Canlet, Marie Tremblay-Franco, Elodie Chaillou, Roselyne Gautier, Véronique Gayrard, Nicole Picard-Hagen, Henri Schroeder, Fabien Jourdan, Daniel Zalko, Catherine Viguié, and Nicolas J. Cabaton
Subjects: Environmental contaminants, Bisphenol A, Fetal exposure, Neurodevelopment, Metabolomic, Sheep, Environmental sciences, GE1-350
Abstract: Abstract: Fetal brain development depends on maternofetal thyroid function. In rodents and sheep, perinatal BPA exposure is associated with maternal and/or fetal thyroid disruption and alterations in central nervous system development as demonstrated by metabolic modulations in the encephala of mice. We hypothesized that a gestational exposure to a low dose of BPA affects maternofetal thyroid function and fetal brain development in a region-specific manner. Pregnant ewes, a relevant model for human thyroid and brain development, were exposed to BPA (5 µg/kg bw/d, sc). The thyroid status of ewes during gestation and term fetuses at delivery was monitored. Fetal brain development was assessed by metabolic fingerprints at birth in 10 areas followed by metabolic network-based analysis. BPA treatment was associated with a significant time-dependent decrease in maternal TT4 serum concentrations. For 8 fetal brain regions, statistical models allowed discriminating BPA-treated from control lambs. Metabolic network computational analysis revealed that prenatal exposure to BPA modulated several metabolic pathways, in particular excitatory and inhibitory amino-acid, cholinergic, energy and lipid homeostasis pathways. These pathways might contribute to BPA-related neurobehavioral and cognitive disorders. Discrimination was particularly clear for the dorsal hippocampus, the cerebellar vermis, the dorsal hypothalamus, the caudate nucleus and the lateral part of the frontal cortex. Compared with previous results in rodents, the use of a larger animal model allowed to examine specific brain areas, and generate evidence of the distinct region-specific effects of fetal BPA exposure on the brain metabolome. These modifications occur concomitantly to subtle maternal thyroid function alteration. The functional link between such moderate thyroid changes and fetal brain metabolomic fingerprints remains to be determined as well as the potential implication of other modes of action triggered by BPA such as estrogenic ones. Our results pave the ways for new scientific strategies aiming at linking environmental endocrine disruption and altered neurodevelopment.
Published: 2022
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6. Gut microbiota derived metabolites contribute to intestinal barrier maturation at the suckling-to-weaning transition

Author: Martin Beaumont, Charlotte Paës, Eloïse Mussard, Christelle Knudsen, Laurent Cauquil, Patrick Aymard, Céline Barilly, Béatrice Gabinaud, Olivier Zemb, Sandra Fourre, Roselyne Gautier, Corinne Lencina, Hélène Eutamène, Vassilia Theodorou, Cécile Canlet, and Sylvie Combes
Subjects: early life, intestinal barrier development, organoids, epithelium, maternal milk, solid food, metabolome, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: In suckling mammals, the onset of solid food ingestion is coincident with the maturation of the gut barrier. This ontogenic process is driven by the colonization of the intestine by the microbiota. However, the mechanisms underlying the microbial regulation of the intestinal development in early life are not fully understood. Here, we studied the co-maturation of the microbiota (composition and metabolic activity) and of the gut barrier at the suckling-to-weaning transition by using a combination of experiments in vivo (suckling rabbit model), ex vivo (Ussing chambers) and in vitro (epithelial cell lines and organoids). The microbiota composition, its metabolic activity, para-cellular epithelial permeability and the gene expression of key components of the gut barrier shifted sharply at the onset of solid food ingestion in vivo, despite milk was still predominant in the diet at that time. We found that cecal content sterile supernatant (i.e. containing a mixture of metabolites) obtained after the onset of solid food ingestion accelerated the formation of the epithelial barrier in Caco-2 cells in vitro and our results suggested that these effects were driven by the bacterial metabolite butyrate. Moreover, the treatment of organoids with cecal content sterile supernatant partially replicated in vitro the effects of solid food ingestion on the epithelial barrier in vivo. Altogether, our results show that the metabolites produced by the microbiota at the onset of solid food ingestion contribute to the maturation of the gut barrier at the suckling-to-weaning transition. Targeting the gut microbiota metabolic activity during this key developmental window might therefore be a promising strategy to promote intestinal homeostasis.
Published: 2020
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7. Transgenerational metabolomic fingerprints in mice ancestrally exposed to the obesogen TBT

Author: Raquel Chamorro-García, Nathalie Poupin, Marie Tremblay-Franco, Cécile Canlet, Riann Egusquiza, Roselyne Gautier, Isabelle Jouanin, Bassem M. Shoucri, Bruce Blumberg, and Daniel Zalko
Subjects: Tributyltin, Endocrine disruptor, Metabolic disruptor, Transgenerational effects, Metabolomics, Obesogen, Environmental sciences, GE1-350
Abstract: Background: Endocrine disrupting chemicals (EDCs) contribute to the etiology of metabolic disorders such as obesity, insulin resistance and hepatic dysfunction. Concern is growing about the consequences of perinatal EDC exposure on disease predisposition later in life. Metabolomics are promising approaches for studying long-term consequences of early life EDC exposure. These approaches allow for the identification and characterization of biomarkers of direct or ancestral exposures that could be diagnostic for individual susceptibility to disease and help to understand mechanisms through which EDCs act. Objectives: We sought to identify metabolomic fingerprints in mice ancestrally exposed to the model obesogen tributyltin (TBT), to assess whether metabolomics could discriminate potential trans-generational susceptibility to obesity and recognize metabolic pathways modulated by ancestral TBT exposure. Methods: We used non-targeted 1H NMR metabolomic analyses of plasma and liver samples collected from male and female mice ancestrally exposed to TBT in two independent transgenerational experiments in which F3 and F4 males became obese when challenged with increased dietary fat. Results: Metabolomics confirmed transgenerational obesogenic effects of environmentally relevant doses of TBT in F3 and F4 males, in two independent studies. Although females never became obese, their specific metabolomic fingerprint evidenced distinct transgenerational effects of TBT in female mice consistent with impaired capacity for liver biotransformation. Discussion: This study is the first application of metabolomics to unveil the transgenerational effects of EDC exposure. Very early, significant changes in the plasma metabolome were observed in animals ancestrally exposed to TBT. These changes preceded the onset of obesogenic effects elicited by increased dietary fat in the TBT groups, and which ultimately resulted in significant changes in the liver metabolome. Development of metabolomic fingerprints could facilitate the identification of individuals carrying the signature of ancestral obesogen exposure that might increase their susceptibility to other risk factor such as increased dietary fat.
Published: 2021
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8. Multiplatform metabolomics for an integrative exploration of metabolic syndrome in older men

Author: Blandine Comte, Stéphanie Monnerie, Marion Brandolini-Bunlon, Cécile Canlet, Florence Castelli, Emeline Chu-Van, Benoit Colsch, François Fenaille, Charlotte Joly, Fabien Jourdan, Natacha Lenuzza, Bernard Lyan, Jean-François Martin, Carole Migné, José A. Morais, Mélanie Pétéra, Nathalie Poupin, Florence Vinson, Etienne Thevenot, Christophe Junot, Pierrette Gaudreau, and Estelle Pujos-Guillot
Subjects: Metabolic syndrome, Metabolomics, Deep phenotyping, Lipidomics, Metabolic signature, Medicine, Medicine (General), R5-920
Abstract: Background: Metabolic syndrome (MetS), a cluster of factors associated with risks of developing cardiovascular diseases, is a public health concern because of its growing prevalence. Considering the combination of concomitant components, their development and severity, MetS phenotypes are largely heterogeneous, inducing disparity in diagnosis. Methods: A case/control study was designed within the NuAge longitudinal cohort on aging. From a 3-year follow-up of 123 stable individuals, we present a deep phenotyping approach based on a multiplatform metabolomics and lipidomics untargeted strategy to better characterize metabolic perturbations in MetS and define a comprehensive MetS signature stable over time in older men. Findings: We characterize significant changes associated with MetS, involving modulations of 476 metabolites and lipids, and representing 16% of the detected serum metabolome/lipidome. These results revealed a systemic alteration of metabolism, involving various metabolic pathways (urea cycle, amino-acid, sphingo- and glycerophospholipid, and sugar metabolisms…) not only intrinsically interrelated, but also reflecting environmental factors (nutrition, microbiota, physical activity…). Interpretation: These findings allowed identifying a comprehensive MetS signature, reduced to 26 metabolites for future translation into clinical applications for better diagnosing MetS.
Published: 2021
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9. Application of Metabolomics to Identify Hepatic Biomarkers of Foie Gras Qualities in Duck

Author: Zohre Mozduri, Bara Lo, Nathalie Marty-Gasset, Ali Akbar Masoudi, Julien Arroyo, Mireille Morisson, Cécile Canlet, Agnès Bonnet, and Cécile M. D. Bonnefont
Subjects: liver, quality, biomarker, metabolomics, foie gras, Physiology, QP1-981
Abstract: Foie gras is a traditional dish in France that contains 50 to 60% of lipids. The high-fat content of the liver improves the organoleptic qualities of foie gras and reduces its technological yield at cooking (TY). As the valorization of the liver as foie gras products is strongly influenced by the TY, classifying the foie gras in their potential technological quality before cooking them is the main challenge for producers. Therefore, the current study aimed to identify hepatic biomarkers of foie gras qualities like liver weight (LW) and TY. A group of 120 male mule ducks was reared and overfed for 6–12 days, and their livers were sampled and analyzed by proton nuclear magnetic resonance (1H-NMR). Eighteen biomarkers of foie gras qualities were identified, nine for LW and TY, five specific to LW, and four specific to TY. All biomarkers were strongly negatively correlated to the liver weights and positively correlated to the technological yield, except for the lactate and the threonine, and also for the creatine that was negatively correlated to foie gras technological quality. As a result, in heavy livers, the liver metabolism was oriented through a reduction of carbohydrate and amino acid metabolisms, and the plasma membrane could be damaged, which may explain the low technological yield of these livers. The detected biomarkers have been strongly discussed with the metabolism of the liver in nonalcoholic steatohepatitis.
Published: 2021
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10. Haem iron reshapes colonic luminal environment: impact on mucosal homeostasis and microbiome through aldehyde formation

Author: Océane C. B. Martin, Maïwenn Olier, Sandrine Ellero-Simatos, Nathalie Naud, Jacques Dupuy, Laurence Huc, Sylviane Taché, Vanessa Graillot, Mathilde Levêque, Valérie Bézirard, Cécile Héliès-Toussaint, Florence Blas Y. Estrada, Valérie Tondereau, Yannick Lippi, Claire Naylies, Lindsey Peyriga, Cécile Canlet, Anne Marie Davila, François Blachier, Laurent Ferrier, Elisa Boutet-Robinet, Françoise Guéraud, Vassilia Théodorou, and Fabrice H. F. Pierre
Subjects: Lipoperoxidation, Barrier function, Metabolites, Dysbiosis, Meat, Microbial ecology, QR100-130
Abstract: Abstract Background The World Health Organization classified processed and red meat consumption as “carcinogenic” and “probably carcinogenic”, respectively, to humans. Haem iron from meat plays a role in the promotion of colorectal cancer in rodent models, in association with enhanced luminal lipoperoxidation and subsequent formation of aldehydes. Here, we investigated the short-term effects of this haem-induced lipoperoxidation on mucosal and luminal gut homeostasis including microbiome in F344 male rats fed with a haem-enriched diet (1.5 μmol/g) 14–21 days. Results Changes in permeability, inflammation, and genotoxicity observed in the mucosal colonic barrier correlated with luminal haem and lipoperoxidation markers. Trapping of luminal haem-induced aldehydes normalised cellular genotoxicity, permeability, and ROS formation on a colon epithelial cell line. Addition of calcium carbonate (2%) to the haem-enriched diet allowed the luminal haem to be trapped in vivo and counteracted these haem-induced physiological traits. Similar covariations of faecal metabolites and bacterial taxa according to haem-induced lipoperoxidation were identified. Conclusions This integrated approach provides an overview of haem-induced modulations of the main actors in the colonic barrier. All alterations were closely linked to haem-induced lipoperoxidation, which is associated with red meat-induced colorectal cancer risk.
Published: 2019
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11. Identification of Plasmatic Biomarkers of Foie Gras Qualities in Duck by Metabolomics

Author: Zohre Mozduri, Nathalie Marty-Gasset, Bara Lo, Ali Akbar Masoudi, Mireille Morisson, Cécile Canlet, Julien Arroyo, Agnès Bonnet, and Cécile M. D. Bonnefont
Subjects: liver, foie gras, quality, biomarker, plasma, metabolomics, Physiology, QP1-981
Abstract: The foie gras is an emblematic product of French gastronomy composed of waterfowl fatty liver. The organoleptic qualities of this product depend on the liver characteristics such as liver weight (LW) and technological yield (TY) at cooking. One of the main issues for producers is to classify the foie gras with high or low technological quality before cooking them. Thus the study aims at identifying biomarkers of these characteristics with non-invasive biomarkers in duck. 1H-NMR (nuclear magnetic resonance of the proton) analyses were performed on plasma of male mule ducks at different time points during the overfeeding period to obtain a large range of liver characteristics so as to identify plasmatic biomarkers of foie gras. We used two methods, one based on bucket data from the 1H-NMR spectra and another one based on the fingerprints of several metabolites. PLS analyses and Linear models were performed to identify biomarkers. We identified 18 biomarkers of liver weight and 15 biomarkers of technological yield. As these two quality parameters were strongly correlated (−0.82), 13 biomarkers were common. The lactate was the most important biomarker, the other were mainly amino acids. Contrary to the amino acids, the lactate increased with the liver weight and decreased with the technological yield. We also identified 5 biomarkers specific to LW (3 carbohydrates: glucuronic acid, mannose, sorbitol and 2 amino acids: glutamic acid and methionine) that were negatively correlated to liver weight. It was of main interest to identify 2 biomarkers specific to the technological yield. Contrary to the isovaleric acid, the valine was negatively correlated to the technological yield.
Published: 2021
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12. Perinatal exposure to a dietary pesticide cocktail does not increase susceptibility to high-fat diet-induced metabolic perturbations at adulthood but modifies urinary and fecal metabolic fingerprints in C57Bl6/J mice

Author: Lorraine Smith, Wendy Klément, Léonie Dopavogui, Frédéric de Bock, Frédéric Lasserre, Sharon Barretto, Céline Lukowicz, Anne Fougerat, Arnaud Polizzi, Benoist Schaal, Bruno Patris, Colette Denis, Guylène Feuillet, Cécile Canlet, Emilien L Jamin, Laurent Debrauwer, Laila Mselli-Lakhal, Nicolas Loiseau, Hervé Guillou, Nicola Marchi, Sandrine Ellero-Simatos, and Laurence Gamet-Payrastre
Subjects: Pesticide cocktail, Metabolism, Perinatal, Metabolomics, Dietary exposure, Environmental sciences, GE1-350
Abstract: Background: We recently demonstrated that chronic dietary exposure to a mixture of pesticides at low-doses induced sexually dimorphic obesogenic and diabetogenic effects in adult mice. Perinatal pesticide exposure may also be a factor in metabolic disease etiology. However, the long-term consequences of perinatal pesticide exposure remain controversial and largely unexplored. Objectives: Here we assessed how perinatal exposure to the same low-dose pesticide cocktail impacted metabolic homeostasis in adult mice. Methods: Six pesticides (boscalid, captan, chlopyrifos, thiachloprid, thiophanate, and ziram) were incorporated in food pellets. During the gestation and lactation periods, female (F0) mice were fed either a pesticide-free or a pesticide-enriched diet at doses exposing them to the tolerable daily intake (TDI) level for each compound, using a 1:1 body weight scaling from humans to mice. All male and female offsprings (F1) were then fed the pesticide-free diet until 18 weeks of age, followed by challenge with a pesticide-free high-fat diet (HFD) for 6 weeks. Metabolic parameters, including body weight, food and water consumption, glucose tolerance, and urinary and fecal metabolomes, were assessed over time. At the end of the experiment, we evaluated energetic metabolism and microbiota activity using biochemical assays, gene expression profiling, and 1H NMR-based metabolomics in the liver, urine, and feces. Results: Perinatal pesticide exposure did not affect body weight or energy homeostasis in 6- and 14-week-old mice. As expected, HFD increased body weight and induced metabolic disorders as compared to a low-fat diet. However, HFD-induced metabolic perturbations were similar between mice with and without perinatal pesticide exposure. Interestingly, perinatal pesticide exposure induced time-specific and sex-specific alterations in the urinary and fecal metabolomes of adult mice, suggesting long-lasting changes in gut microbiota. Conclusions: Perinatal pesticide exposure induced sustained sexually dimorphic perturbations of the urinary and fecal metabolic fingerprints, but did not significantly influence the development of HFD-induced metabolic diseases.
Published: 2020
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13. Statistical Integration of ‘Omics Data Increases Biological Knowledge Extracted from Metabolomics Data: Application to Intestinal Exposure to the Mycotoxin Deoxynivalenol

Author: Marie Tremblay-Franco, Cécile Canlet, Philippe Pinton, Yannick Lippi, Roselyne Gautier, Claire Naylies, Manon Neves, Isabelle P. Oswald, Laurent Debrauwer, and Imourana Alassane-Kpembi
Subjects: mycotoxin exposure 1, transcriptomics 2, metabolomics 3, statistical integration 4, Microbiology, QR1-502
Abstract: The effects of low doses of toxicants are often subtle and information extracted from metabolomic data alone may not always be sufficient. As end products of enzymatic reactions, metabolites represent the final phenotypic expression of an organism and can also reflect gene expression changes caused by this exposure. Therefore, the integration of metabolomic and transcriptomic data could improve the extracted biological knowledge on these toxicants induced disruptions. In the present study, we applied statistical integration tools to metabolomic and transcriptomic data obtained from jejunal explants of pigs exposed to the food contaminant, deoxynivalenol (DON). Canonical correlation analysis (CCA) and self-organizing map (SOM) were compared for the identification of correlated transcriptomic and metabolomic features, and O2-PLS was used to model the relationship between exposure and selected features. The integration of both ‘omics data increased the number of discriminant metabolites discovered (39) by about 10 times compared to the analysis of the metabolomic dataset alone (3). Besides the disturbance of energy metabolism previously reported, assessing correlations between both functional levels revealed several other types of damage linked to the intestinal exposure to DON, including the alteration of protein synthesis, oxidative stress, and inflammasome activation. This confirms the added value of integration to enrich the biological knowledge extracted from metabolomics.
Published: 2021
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14. Postprandial NMR-Based Metabolic Exchanges Reflect Impaired Phenotypic Flexibility across Splanchnic Organs in the Obese Yucatan Mini-Pig

Author: Marie Tremblay-Franco, Nathalie Poupin, Aurélien Amiel, Cécile Canlet, Didier Rémond, Laurent Debrauwer, Dominique Dardevet, Fabien Jourdan, Isabelle Savary-Auzeloux, and Sergio Polakof
Subjects: arteriovenous differences, postprandial, high fat-high sucrose diet, mini-pigs, energy metabolism, metabolomics, Nutrition. Foods and food supply, TX341-641
Abstract: The postprandial period represents one of the most challenging phenomena in whole-body metabolism, and it can be used as a unique window to evaluate the phenotypic flexibility of an individual in response to a given meal, which can be done by measuring the resilience of the metabolome. However, this exploration of the metabolism has never been applied to the arteriovenous (AV) exploration of organs metabolism. Here, we applied an AV metabolomics strategy to evaluate the postprandial flexibility across the liver and the intestine of mini-pigs subjected to a high fat–high sucrose (HFHS) diet for 2 months. We identified for the first time a postprandial signature associated to the insulin resistance and obesity outcomes, and we showed that the splanchnic postprandial metabolome was considerably affected by the meal and the obesity condition. Most of the changes induced by obesity were observed in the exchanges across the liver, where the metabolism was reorganized to maintain whole body glucose homeostasis by routing glucose formed de novo from a large variety of substrates into glycogen. Furthermore, metabolites related to lipid handling and energy metabolism showed a blunted postprandial response in the obese animals across organs. Finally, some of our results reflect a loss of flexibility in response to the HFHS meal challenge in unsuspected metabolic pathways that must be further explored as potential new events involved in early obesity and the onset of insulin resistance.
Published: 2020
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15. Important Considerations for Sample Collection in Metabolomics Studies with a Special Focus on Applications to Liver Functions

Author: Lorraine Smith, Joran Villaret-Cazadamont, Sandrine P. Claus, Cécile Canlet, Hervé Guillou, Nicolas J. Cabaton, and Sandrine Ellero-Simatos
Subjects: metabolomics, standard operating procedures, urine, blood, feces, tissue, cells, liver function, Microbiology, QR1-502
Abstract: Metabolomics has found numerous applications in the study of liver metabolism in health and disease. Metabolomics studies can be conducted in a variety of biological matrices ranging from easily accessible biofluids such as urine, blood or feces, to organs, tissues or even cells. Sample collection and storage are critical steps for which standard operating procedures must be followed. Inappropriate sample collection or storage can indeed result in high variability, interferences with instrumentation or degradation of metabolites. In this review, we will first highlight important general factors that should be considered when planning sample collection in the study design of metabolomic studies, such as nutritional status and circadian rhythm. Then, we will discuss in more detail the specific procedures that have been described for optimal pre-analytical handling of the most commonly used matrices (urine, blood, feces, tissues and cells).
Published: 2020
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16. Evaluation of sample preparation methods for NMR-based metabolomics of cow milk

Author: Bénédict Yanibada, Hamid Boudra, Laurent Debrauwer, Cécile Martin, Diego P. Morgavi, and Cécile Canlet
Subjects: Nutrition, Food analysis, Analytical chemistry, Science (General), Q1-390, Social sciences (General), H1-99
Abstract: The quality of milk metabolome analyzed by nuclear magnetic resonance (NMR) is greatly influenced by the way samples are prepared. Although this analytical method is increasingly used to study milk metabolites, a thorough examination of available sample preparation protocols for milk has not been reported yet. We evaluated the performance of eight milk preparation methods namely (1) raw milk without any processing; (2) skimmed milk; (3) ultrafiltered milk; (4) skimming followed by ultrafiltration; (5) ultracentrifuged milk; (6) methanol; (7) dichloromethane; and (8) methanol/dichloromethane, in terms of spectra quality, repeatability, signal-to-noise ratio, extraction efficiency and yield criteria. A pooled sample of milk was used for all protocols. Skimming, ultracentrifugation and unprocessed milk protocols showed poor NMR spectra quality. Protocols involving multiple steps, namely methanol/dichloromethane extraction, and skimming followed by ultrafiltration produced inadequate results for signal-to-noise ratio parameter. Methanol and skimming associated to ultrafiltration provided good repeatability results compared to the other protocols. Chemical-based sample preparation protocols, particularly methanol, showed more efficient metabolite extraction compared to physical preparation methods. When considering all evaluation parameters, the methanol extraction protocol proved to be the best method. As a proof of utility, methanol protocol was then applied to milk samples from dairy cows fed a diet with or without a feed additive, showing a clear separation between the two groups of cows.
Published: 2018
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17. An Untargeted Metabolomics Approach to Investigate the Metabolic Modulations of HepG2 Cells Exposed to Low Doses of Bisphenol A and 17β-Estradiol

Author: Nicolas J. Cabaton, Nathalie Poupin, Cécile Canlet, Marie Tremblay-Franco, Marc Audebert, Jean-Pierre Cravedi, Anne Riu, Fabien Jourdan, and Daniel Zalko
Subjects: HepG2, metabolomics, BPA, 17β-estradiol, endocrine disruption, metabolic network, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: The model xeno-estrogen bisphenol A (BPA) has been extensively studied over the past two decades, contributing to major advances in the field of endocrine disrupting chemicals research. Besides its well documented adverse effects on reproduction and development observed in rodents, latest studies strongly suggest that BPA disrupts several endogenous metabolic pathways, with suspected steatogenic and obesogenic effects. BPA's adverse effects on reproduction are attributed to its ability to activate estrogen receptors (ERs), but its effects on metabolism and its mechanism(s) of action at low doses are so far only marginally understood. Metabolomics based approaches are increasingly used in toxicology to investigate the biological changes induced by model toxicants and chemical mixtures, to identify markers of toxicity and biological effects. In this study, we used proton nuclear magnetic resonance (1H-NMR) based untargeted metabolite profiling, followed by multivariate statistics and computational analysis of metabolic networks to examine the metabolic modulation induced in human hepatic cells (HepG2) by an exposure to low and very low doses of BPA (10−6M, 10−9M, and 10−12M), vs. the female reference hormone 17β-estradiol (E2, 10−9M, 10−12M, and 10−15M). Metabolomic analysis combined to metabolic network reconstruction highlighted different mechanisms at lower doses of exposure. At the highest dose, our results evidence that BPA shares with E2 the capability to modulate several major metabolic routes that ensure cellular functions and detoxification processes, although the effects of the model xeno-estrogen and of the natural hormone can still be distinguished.
Published: 2018
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18. Metabolome disruption of pregnant rats and their offspring resulting from repeated exposure to a pesticide mixture representative of environmental contamination in Brittany.

Author: Nathalie Bonvallot, Cécile Canlet, Florence Blas-Y-Estrada, Roselyne Gautier, Marie Tremblay-Franco, Sylvie Chevolleau, Sylvaine Cordier, and Jean-Pierre Cravedi
Subjects: Medicine, Science
Abstract: The use of pesticides exposes humans to numerous harmful molecules. Exposure in early-life may be responsible for adverse effects in later life. This study aimed to assess the metabolic modifications induced in pregnant rats and their offspring by a pesticide mixture representative of human exposure. Ten pregnant rats were exposed to a mixture of eight pesticides: acetochlor (246 μg/kg bw/d) + bromoxynil (12 μg/kg bw/d) + carbofuran (22.5 μg/kg bw/d) + chlormequat (35 μg/kg bw/d) + ethephon (22.5 μg/kg bw/d) + fenpropimorph (15.5 μg/kg bw/d) + glyphosate (12 μg/kg bw/d) + imidacloprid (12.5 μg/kg bw/d) representing the main environmental pesticide exposure in Brittany (France) in 2004. Another group of 10 pregnant rats served as controls. Females were fed ad libitum from early pregnancy, which is from gestational day (GD) 4 to GD 21. Urine samples were collected at GD 15. At the end of the exposure, mothers and pups were euthanized and blood, liver, and brain samples collected. 1H NMR-based metabolomics and GC-FID analyses were performed and PCA and PLS-DA used to discriminate between control and exposed groups. Metabolites for which the levels were significantly modified were then identified using the Kruskal-Wallis test, and p-values were adjusted for multiple testing correction using the False Discovery Rate. The metabolomics analysis revealed many differences between dams of the two groups, especially in the plasma, liver and brain. The modified metabolites are involved in TCA cycle, energy production and storage, lipid and carbohydrate metabolism, and amino-acid metabolism. These modifications suggest that the pesticide mixture may induce oxidative stress associated with mitochondrial dysfunction and the impairment of glucose and lipid metabolism. These observations may reflect liver dysfunction with increased relative liver weight and total lipid content. Similar findings were observed for glucose and energy metabolism in the liver of the offspring, and oxidative stress was also suggested in the brains of male offspring.
Published: 2018
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19. Quantification of Lipids: Model, Reality, and Compromise

Author: Spiro Khoury, Cécile Canlet, Marlène Z. Lacroix, Olivier Berdeaux, Juliette Jouhet, and Justine Bertrand-Michel
Subjects: lipidomic, mass spectrometry, nuclear magnetic resonance, quantification, universal detector, Microbiology, QR1-502
Abstract: Lipids are key molecules in various biological processes, thus their quantification is a crucial point in a lot of studies and should be taken into account in lipidomics development. This family is complex and presents a very large diversity of structures, so analyzing and quantifying all this diversity is a real challenge. In this review, the different techniques to analyze lipids will be presented: from nuclear magnetic resonance (NMR) to mass spectrometry (with and without chromatography) including universal detectors. First of all, the state of the art of quantification, with the definitions of terms and protocol standardization, will be presented with quantitative lipidomics in mind, and then technical considerations and limitations of analytical chemistry’s tools, such as NMR, mass spectrometry and universal detectors, will be discussed, particularly in terms of absolute quantification.
Published: 2018
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20. Dynamic Metabolic Disruption in Rats Perinatally Exposed to Low Doses of Bisphenol-A.

Author: Marie Tremblay-Franco, Nicolas J Cabaton, Cécile Canlet, Roselyne Gautier, Cheryl M Schaeberle, Fabien Jourdan, Carlos Sonnenschein, Florence Vinson, Ana M Soto, and Daniel Zalko
Subjects: Medicine, Science
Abstract: Along with the well-established effects on fertility and fecundity, perinatal exposure to endocrine disrupting chemicals, and notably to xeno-estrogens, is strongly suspected of modulating general metabolism. The metabolism of a perinatally exposed individual may be durably altered leading to a higher susceptibility of developing metabolic disorders such as obesity and diabetes; however, experimental designs involving the long term study of these dynamic changes in the metabolome raise novel challenges. 1H-NMR-based metabolomics was applied to study the effects of bisphenol-A (BPA, 0; 0.25; 2.5, 25 and 250 μg/kg BW/day) in rats exposed perinatally. Serum and liver samples of exposed animals were analyzed on days 21, 50, 90, 140 and 200 in order to explore whether maternal exposure to BPA alters metabolism. Partial Least Squares-Discriminant Analysis (PLS-DA) was independently applied to each time point, demonstrating a significant pair-wise discrimination for liver as well as serum samples at all time-points, and highlighting unequivocal metabolic shifts in rats perinatally exposed to BPA, including those exposed to lower doses. In BPA exposed animals, metabolism of glucose, lactate and fatty acids was modified over time. To further explore dynamic variation, ANOVA-Simultaneous Component Analysis (A-SCA) was used to separate data into blocks corresponding to the different sources of variation (Time, Dose and Time*Dose interaction). A-SCA enabled the demonstration of a dynamic, time/age dependent shift of serum metabolome throughout the rats' lifetimes. Variables responsible for the discrimination between groups clearly indicate that BPA modulates energy metabolism, and suggest alterations of neurotransmitter signaling, the latter finding being compatible with the neurodevelopmental effect of this xenoestrogen. In conclusion, long lasting metabolic effects of BPA could be characterized over 200 days, despite physiological (and thus metabolic) changes connected with sexual maturation and aging.
Published: 2015
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21. Specific Metabolic Fingerprint of a Dietary Exposure to a Very Low Dose of Endosulfan

Author: Cécile Canlet, Marie Tremblay-Franco, Roselyne Gautier, Jérôme Molina, Benjamin Métais, Florence Blas-Y Estrada, and Laurence Gamet-Payrastre
Subjects: Toxicology. Poisons, RA1190-1270
Abstract: Like other persistent organochlorine pesticides, endosulfan residues have been detected in foods including fruit, vegetables, and fish. The aim of our study was to assess the impact of a dietary exposure to low doses of endosulfan from foetal development until adult age on metabolic homeostasis in mice and to identify biomarkers of exposure using an 1H-NMR-based metabonomic approach in various tissues and biofluids. We report in both genders an increase in plasma glucose as well as changes in levels of factors involved in the regulation of liver oxidative stress, confirming the prooxidant activities of this compound. Some metabolic changes were distinct in males and females. For example in plasma, a decrease in lipid LDL and choline content was only observed in female. Lactate levels in males were significantly increased. In conclusion, our results show that metabolic changes in liver could be linked to the onset of pathologies like diabetes and insulin resistance. Moreover from our results it appears that the NMR-based metabonomic approach could be useful for the characterization in plasma of a dietary exposure to low dose of pesticide in human.
Published: 2013
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22. Metabolomics tools for describing complex pesticide exposure in pregnant women in Brittany (France).

Author: Nathalie Bonvallot, Marie Tremblay-Franco, Cécile Chevrier, Cécile Canlet, Charline Warembourg, Jean-Pierre Cravedi, and Sylvaine Cordier
Subjects: Medicine, Science
Abstract: BACKGROUND: The use of pesticides and the related environmental contaminations can lead to human exposure to various molecules. In early-life, such exposures could be responsible for adverse developmental effects. However, human health risks associated with exposure to complex mixtures are currently under-explored. OBJECTIVE: THIS PROJECT AIMS AT ANSWERING THE FOLLOWING QUESTIONS: What is the influence of exposures to multiple pesticides on the metabolome? What mechanistic pathways could be involved in the metabolic changes observed? METHODS: Based on the PELAGIE cohort (Brittany, France), 83 pregnant women who provided a urine sample in early pregnancy, were classified in 3 groups according to the surface of land dedicated to agricultural cereal activities in their town of residence. Nuclear magnetic resonance-based metabolomics analyses were performed on urine samples. Partial Least Squares Regression-Discriminant Analysis (PLS-DA) and polytomous regressions were used to separate the urinary metabolic profiles from the 3 exposure groups after adjusting for potential confounders. RESULTS: The 3 groups of exposure were correctly separated with a PLS-DA model after implementing an orthogonal signal correction with pareto standardizations (R2 = 90.7% and Q2 = 0.53). After adjusting for maternal age, parity, body mass index and smoking habits, the most statistically significant changes were observed for glycine, threonine, lactate and glycerophosphocholine (upward trend), and for citrate (downward trend). CONCLUSION: This work suggests that an exposure to complex pesticide mixtures induces modifications of metabolic fingerprints. It can be hypothesized from identified discriminating metabolites that the pesticide mixtures could increase oxidative stress and disturb energy metabolism.
Published: 2013
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23. Trypacidin, a spore-borne toxin from Aspergillus fumigatus, is cytotoxic to lung cells.

Author: Thierry Gauthier, Xiaodi Wang, Joice Sifuentes Dos Santos, Athanasios Fysikopoulos, Souria Tadrist, Cécile Canlet, Marie Pierre Artigot, Nicolas Loiseau, Isabelle P Oswald, and Olivier Puel
Subjects: Medicine, Science
Abstract: Inhalation of Aspergillus fumigatus conidia can cause severe aspergillosis in immunosuppressed people. A. fumigatus produces a large number of secondary metabolites, some of which are airborne by conidia and whose toxicity to the respiratory tract has not been investigated. We found that spores of A. fumigatus contain five main compounds, tryptoquivaline F, fumiquinazoline C, questin, monomethylsulochrin and trypacidin. Fractionation of culture extracts using RP-HPLC and LC-MS showed that samples containing questin, monomethylsulochrin and trypacidin were toxic to the human A549 lung cell line. These compounds were purified and their structure verified using NMR in order to compare their toxicity against A549 cells. Trypacidin was the most toxic, decreasing cell viability and triggering cell lysis, both effects occurring at an IC₅₀ close to 7 µM. Trypacidin toxicity was also observed in the same concentration range on human bronchial epithelial cells. In the first hour of exposure, trypacidin initiates the intracellular formation of nitric oxide (NO) and hydrogen peroxide (H₂O₂). This oxidative stress triggers necrotic cell death in the following 24 h. The apoptosis pathway, moreover, was not involved in the cell death process as trypacidin did not induce apoptotic bodies or a decrease in mitochondrial membrane potential. This is the first time that the toxicity of trypacidin to lung cells has been reported.
Published: 2012
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24. Immunological and metabolomic impacts of administration of Cry1Ab protein and MON 810 maize in mouse.

Author: Karine Adel-Patient, Valeria D Guimaraes, Alain Paris, Marie-Françoise Drumare, Sandrine Ah-Leung, Patricia Lamourette, Marie-Claire Nevers, Cécile Canlet, Jérôme Molina, Hervé Bernard, Christophe Créminon, and Jean-Michel Wal
Subjects: Medicine, Science
Abstract: We have investigated the immunological and metabolomic impacts of Cry1Ab administration to mice, either as a purified protein or as the Cry1Ab-expressing genetically modified (GM) MON810 maize. Humoral and cellular specific immune responses induced in BALB/cJ mice after intra-gastric (i.g.) or intra-peritoneal (i.p.) administration of purified Cry1Ab were analyzed and compared with those induced by proteins of various immunogenic and allergic potencies. Possible unintended effects of the genetic modification on the pattern of expression of maize natural allergens were studied using IgE-immunoblot and sera from maize-allergic patients. Mice were experimentally sensitized (i.g. or i.p. route) with protein extracts from GM or non-GM maize, and then anti-maize proteins and anti-Cry1Ab-induced immune responses were analyzed. In parallel, longitudinal metabolomic studies were performed on the urine of mice treated via the i.g. route. Weak immune responses were observed after i.g. administration of the different proteins. Using the i.p. route, a clear Th2 response was observed with the known allergenic proteins, whereas a mixed Th1/Th2 immune response was observed with immunogenic protein not known to be allergenic and with Cry1Ab. This then reflects protein immunogenicity in the BALB/c Th2-biased mouse strain rather than allergenicity. No difference in natural maize allergen profiles was evidenced between MON810 and its non-GM comparator. Immune responses against maize proteins were quantitatively equivalent in mice treated with MON810 vs the non-GM counterpart and no anti-Cry1Ab-specific immune response was detected in mice that received MON810. Metabolomic studies showed a slight "cultivar" effect, which represented less than 1% of the initial metabolic information. Our results confirm the immunogenicity of purified Cry1Ab without evidence of allergenic potential. Immunological and metabolomic studies revealed slight differences in mouse metabolic profiles after i.g. administration of MON810 vs its non-GM counterpart, but no significant unintended effect of the genetic modification on immune responses was seen.
Published: 2011
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25. Milk metabolome reveals variations on enteric methane emissions from dairy cows fed a specific inhibitor of the methanogenesis pathway

Author: Diego P. Morgavi, Hamid Boudra, Bénédict Yanibada, Stéphanie Durand, Ulli Hohenester, Fabien Jourdan, Cécile Canlet, Anne Ferlay, Mélanie Pétéra, LESUR, Hélène, Unité Mixte de Recherche sur les Herbivores - UMR 1213 (UMRH), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Plateforme Exploration du Métabolisme-MetaboHUB (PFEM-MetaboHUB), Institut National de la Recherche Agronomique (INRA)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Metatoul AXIOM (E20 ), MetaboHUB-MetaToul, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-ToxAlim (ToxAlim), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Métabolisme et Xénobiotiques (ToxAlim-MeX), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), MetaToul-MetaboHUB, Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Plateforme Exploration du Métabolisme (PFEM), Institut National de la Recherche Agronomique (INRA)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-MetaboHUB-Clermont, MetaboHUB-MetaboHUB, Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-ToxAlim (ToxAlim), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3)
Subjects: Rumen, multiplatform metabolomics, [SDV.BA] Life Sciences [q-bio]/Animal biology, Methanogenesis, [SDV]Life Sciences [q-bio], Gas Chromatography-Mass Spectrometry, 03 medical and health sciences, Metabolomics, Lactation, Genetics, Metabolome, medicine, Animals, [SDV.SA.SPA] Life Sciences [q-bio]/Agricultural sciences/Animal production studies, Food science, microbial metabolite, 030304 developmental biology, 2. Zero hunger, milk, 0303 health sciences, methane biomarker, Chemistry, dairy cow, [SDV.BA]Life Sciences [q-bio]/Animal biology, 0402 animal and dairy science, 04 agricultural and veterinary sciences, Metabolism, 040201 dairy & animal science, Diet, [SDV] Life Sciences [q-bio], Metabolic pathway, medicine.anatomical_structure, 13. Climate action, [SDV.SA.SPA]Life Sciences [q-bio]/Agricultural sciences/Animal production studies, Fermentation, Cattle, Female, Animal Science and Zoology, Gas chromatography, Methane, Food Science
Abstract: International audience; Metabolome profiling in biological fluids is an interesting approach for exploring markers of methane emissions in ruminants. In this study, a multiplatform metabolomics approach was used for investigating changes in milk metabolic profiles related to methanogenesis in dairy cows. For this purpose, 25 primiparous Holstein cows at similar lactation stage were fed the same diet supplemented with (treated, n = 12) or without (control, n = 13) a specific antimethanogenic additive that reduced enteric methane production by 23% with no changes in intake, milk production, and health status. The study lasted 6 wk, with sampling and measures performed in wk 5 and 6. Milk samples were analyzed using 4 complementary analytical methods, including 2 untargeted (nuclear magnetic resonance and liquid chromatography coupled to a quadrupole-time-of-flight mass spectrometer) and 2 targeted (liquid chromatography-tandem mass spectrometry and gas chromatography coupled to a flame ionization detector) approaches. After filtration, variable selection and normalization data from each analytical platform were then analyzed using multivariate orthogonal partial least square discriminant analysis. All 4 analytical methods were able to differentiate cows from treated and control groups. Overall, 38 discriminant metabolites were identified, which affected 10 metabolic pathways including methane metabolism. Some of these metabolites such as dimethylsulfoxide, dimethylsulfone, and citramalic acid, detected by nuclear magnetic resonance or liquid chromatography-mass spectrometry methods, originated from the rumen microbiota or had a microbial-host animal co-metabolism that could be associated with methanogenesis. Also, discriminant milk fatty acids detected by targeted gas chromatography were mostly of ruminal microbial origin. Other metabolites and metabolic pathways significantly affected were associated with AA metabolism. These findings provide new insight on the potential role of milk metabolites as indicators of enteric methane modifications in dairy cows.
Published: 2021

26. PeakForest: a multi-platform digital infrastructure for interoperable metabolite spectral data and metadata management

Author: Nils Paulhe, Cécile Canlet, Annelaure Damont, Lindsay Peyriga, Stéphanie Durand, Catherine Deborde, Sandra Alves, Stephane Bernillon, Thierry Berton, Raphael Bir, Alyssa Bouville, Edern Cahoreau, Delphine Centeno, Robin Costantino, Laurent Debrauwer, Alexis Delabrière, Christophe Duperier, Sylvain Emery, Amelie Flandin, Ulli Hohenester, Daniel Jacob, Charlotte Joly, Cyril Jousse, Marie Lagree, Nadia Lamari, Marie Lefebvre, Claire Lopez-Piffet, Bernard Lyan, Mickael Maucourt, Carole Migne, Marie-Francoise Olivier, Estelle Rathahao-Paris, Pierre Petriacq, Julie Pinelli, Léa Roch, Pierrick Roger, Simon Roques, Jean-Claude Tabet, Marie Tremblay-Franco, Mounir Traïkia, Anna Warnet, Vanessa Zhendre, Dominique Rolin, Fabien Jourdan, Etienne Thévenot, Annick Moing, Emilien Jamin, François Fenaille, Christophe Junot, Estelle Pujos-Guillot, Franck Giacomoni, Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Metatoul AXIOM (E20 ), MetaboHUB-MetaToul, MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-ToxAlim (ToxAlim), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), ToxAlim (ToxAlim), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Plateforme Exploration du Métabolisme (PFEM), Institut National de la Recherche Agronomique (INRA)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-MetaboHUB-Clermont, MetaboHUB-MetaboHUB, Biologie du fruit et pathologie (BFP), Université de Bordeaux (UB)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Plateforme Bordeaux Metabolome, Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-MetaboHUB-Bordeaux, MetaToul FluxoMet (TBI-MetaToul), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Toulouse Biotechnology Institute (TBI), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), The PeakForest project is supported by the French National Facility in Metabolomics & Fluxomics, MetaboHUB (11-INBS-0010), launched by the French Ministry of Research and Higher Education and the French ANR funding agency within the Programme 'Investissements d’Avenir', and ANR-11-INBS-0010,METABOHUB,Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation(2011)
Subjects: Metadata, [INFO.INFO-DB]Computer Science [cs]/Databases [cs.DB], Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Clinical Biochemistry, Metabolite identification, Spectral library, Interoperability, Biochemistry, Mass Spectrometry, Curation, Database, Metabolome, [CHIM]Chemical Sciences, Metabolomics, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Data Curation, FAIR
Abstract: Introduction Accuracy of feature annotation and metabolite identification in biological samples is a key element in metabolomics research. However, the annotation process is often hampered by the lack of spectral reference data in experimental conditions, as well as logistical difficulties in the spectral data management and exchange of annotations between laboratories. Objectives To design an open-source infrastructure allowing hosting both nuclear magnetic resonance (NMR) and mass spectra (MS), with an ergonomic Web interface and Web services to support metabolite annotation and laboratory data management. Methods We developed the PeakForest infrastructure, an open-source Java tool with automatic programming interfaces that can be deployed locally to organize spectral data for metabolome annotation in laboratories. Standardized operating procedures and formats were included to ensure data quality and interoperability, in line with international recommendations and FAIR principles. Results PeakForest is able to capture and store experimental spectral MS and NMR metadata as well as collect and display signal annotations. This modular system provides a structured database with inbuilt tools to curate information, browse and reuse spectral information in data treatment. PeakForest offers data formalization and centralization at the laboratory level, facilitating shared spectral data across laboratories and integration into public databases. Conclusion PeakForest is a comprehensive resource which addresses a technical bottleneck, namely large-scale spectral data annotation and metabolite identification for metabolomics laboratories with multiple instruments. PeakForest databases can be used in conjunction with bespoke data analysis pipelines in the Galaxy environment, offering the opportunity to meet the evolving needs of metabolomics research. Developed and tested by the French metabolomics community, PeakForest is freely-available at https://github.com/peakforest.
Published: 2022

27. Gut microbiota derived metabolites contribute to intestinal barrier maturation at the suckling-to-weaning transition

Author: Vassilia Theodorou, Helene Eutamene, Cécile Canlet, Céline Barilly, Patrick Aymard, Sylvie Combes, Béatrice Gabinaud, Eloïse Mussard, Sandra Fourre, Charlotte Paës, Corinne Lencina, Roselyne Gautier, Martin Beaumont, Laurent Cauquil, Christelle Knudsen, Olivier Zemb, Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Génome et Transcriptome - Plateforme Génomique ( GeT-PlaGe), Plateforme Génome & Transcriptome (GET), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), MetaToul-MetaboHUB, Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), ToxAlim (ToxAlim), Neuro-Gastroentérologie & Nutrition (ToxAlim-NGN), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), GeT PlaGe, Genotoul (GeT PlaGe), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3)
Subjects: 0301 basic medicine, Male, Metabolite, [SDV]Life Sciences [q-bio], RC799-869, Gut flora, chemistry.chemical_compound, Eating, 0302 clinical medicine, RNA, Ribosomal, 16S, solid food, Ingestion, Intestinal Mucosa, Cecum, organoids, biology, digestive, oral, and skin physiology, Gastroenterology, Diseases of the digestive system. Gastroenterology, Cell biology, Animals, Suckling, Infectious Diseases, Milk, [SDV.TOX]Life Sciences [q-bio]/Toxicology, 030211 gastroenterology & hepatology, metabolome, Rabbits, Research Article, Microbiology (medical), Butyrate, Weaning, Microbiology, digestive system, maternal milk, Early life, Permeability, 03 medical and health sciences, In vivo, Metabolome, Organoid, Animals, Humans, intestinal barrier development, Bacteria, Genes, rRNA, biology.organism_classification, Gastrointestinal Microbiome, 030104 developmental biology, chemistry, Gene Expression Regulation, Research Paper/Report, Caco-2 Cells, epithelium, Transcriptome, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Ex vivo
Abstract: International audience; In suckling mammals, the onset of solid food ingestion is coincident with the maturation of the gut barrier. This ontogenic process is driven by the colonization of the intestine by the microbiota. However, the mechanisms underlying the microbial regulation of the intestinal development in early life are not fully understood. Here, we studied the co-maturation of the microbiota (composition and metabolic activity) and of the gut barrier at the suckling-to-weaning transition by using a combination of experiments in vivo (suckling rabbit model), ex vivo (Ussing chambers) and in vitro (epithelial cell lines and organoids). The microbiota composition, its metabolic activity, para-cellular epithelial permeability and the gene expression of key components of the gut barrier shifted sharply at the onset of solid food ingestion in vivo, despite milk was still predominant in the diet at that time. We found that cecal content sterile supernatant (i.e. containing a mixture of metabolites) obtained after the onset of solid food ingestion accelerated the formation of the epithelial barrier in Caco-2 cells in vitro and our results suggested that these effects were driven by the bacterial metabolite butyrate. Moreover, the treatment of organoids with cecal content sterile supernatant partially replicated in vitro the effects of solid food ingestion on the epithelial barrier in vivo. Altogether, our results show that the metabolites produced by the microbiota at the onset of solid food ingestion contribute to the maturation of the gut barrier at the suckling-to-weaning transition. Targeting the gut microbiota metabolic activity during this key developmental window might therefore be a promising strategy to promote intestinal homeostasis.
Published: 2020

28. Lactobacillus supports Clostridiales to restrict gut colonization by multidrug-resistant Enterobacteriaceae

Author: Ana Djukovic, María José Garzón, Cécile Canlet, Vitor Cabral, Rym Lalaoui, Marc García-Garcerá, Julia Rechenberger, Marie Tremblay-Franco, Iván Peñaranda, Leonor Puchades-Carrasco, Antonio Pineda-Lucena, Eva María González-Barberá, Miguel Salavert, José Luis López-Hontangas, Miguel Á. Sanz, Jaime Sanz, Bernhard Kuster, Jean-Marc Rolain, Laurent Debrauwer, Karina B. Xavier, Joao B. Xavier, Carles Ubeda, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana [Espagne] (FISABIO), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Metatoul AXIOM (E20 ), MetaboHUB-MetaToul, MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-ToxAlim (ToxAlim), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Instituto Gulbenkian de Ciência [Oeiras] (IGC), Fundação Calouste Gulbenkian, Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Université de Lausanne = University of Lausanne (UNIL), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Instituto de Investigación Sanitaria de Aragón [Zaragoza] (IIS Aragón), Universidad de Navarra [Pamplona] (UNAV), Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, Instituto de Salud Carlos III [Madrid] (ISC), Memorial Sloan-Kettering Cancer Institute, Memorial Sloane Kettering Cancer Center [New York], C.U. was supported by the InfectERA-ERANET-Acciones complementarias grant [PCIN-2015-094] from the Spanish Ministerio de Economia y Competitividad and the 7th Research framework program from EU, grants from Conselleria d'Innovacio, Universitats, Ciencia i Societat Digital [AICO/2019/266, CIPROM/2021/053] and a grant from the Spanish MICINN [PID2020-120292RB-I00]. A.D. was supported by a Boehringer Ingelheim Fonds travel grant, and with J.B.X. by grant R01 AI137269/AI/NIAID from the US National Institutes of Health. B.K. was supported by the BMBF FloraStopMRE grant [031L0089]. V.C. was supported by an European Commission grant [MSCA-IF-2018-843183]. J.S. was supported by an InfectERA-ERANET-Acciones complementarias de programacion conjunta internacional grant (AC15/00070) and Proyectos de Investigacion en Salud del Instituto Carlos III (PI18/00280). K.B.X. was supported by FundacAo para a Ciencia e a Tecnologia grant (InfectERA/0004/2015). J.M.R. was supported by ANR FloraStopInfectMRE project., Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-ToxAlim (ToxAlim), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), and LESUR, Hélène
Subjects: Clostridiales, Multidisciplinary, [SDV]Life Sciences [q-bio], General Physics and Astronomy, General Chemistry, General Biochemistry, Genetics and Molecular Biology, Anti-Bacterial Agents, [SDV] Life Sciences [q-bio], Butyrates, Lactobacillus, Mice, Enterobacteriaceae, Animals, Prospective Studies
Abstract: Infections by multidrug-resistant Enterobacteriaceae (MRE) are life-threatening to patients. The intestinal microbiome protects against MRE colonization, but antibiotics cause collateral damage to commensals and open the way to colonization and subsequent infection. Despite the significance of this problem, the specific commensals and mechanisms that restrict MRE colonization remain largely unknown. Here, by performing a multi-omic prospective study of hospitalized patients combined with mice experiments, we find that Lactobacillus is key, though not sufficient, to restrict MRE gut colonization. Lactobacillus rhamnosus and murinus increase the levels of Clostridiales bacteria, which induces a hostile environment for MRE growth through increased butyrate levels and reduced nutrient sources. This mechanism of colonization resistance, an interaction between Lactobacillus spp. and Clostridiales involving cooperation between microbiota members, is conserved in mice and patients. These results stress the importance of exploiting microbiome interactions for developing effective probiotics that prevent infections in hospitalized patients.
Published: 2021

29. Slightly different metabolomic profiles are associated with high or low weights duck foie gras

Author: Hervé Rémignon, Renaud Domitile, Hélène Manse, Nathalie Marty-Gasset, Cécile Canlet, and Bara Lo
Subjects: medicine.medical_specialty, Chemistry, Cholesterol, Glucose uptake, Fatty liver, Lipid metabolism, Metabolism, medicine.disease, medicine.disease_cause, chemistry.chemical_compound, Metabolomics, Endocrinology, Liver metabolism, Internal medicine, medicine, Oxidative stress
Abstract: Understanding the evolution of fatty liver metabolism of ducks is a recurrent issue for researchers and industry. Indeed, the increase in weight during the overfeeding period leads to an important change in the liver metabolism. However, liver weight is highly variable at the end of overfeeding within a batch of animals reared, force-fed and slaughtered in the same way. For this study, we performed a proton nuclear magnetic resonance (1H-NMR) analysis on two classes of fatty liver samples, called low-weight liver (weight between 550 and 599 g) and high-weight liver (weight above 700 g). The aim of this study was to identify the differences in metabolism between two classes of liver weight (low and high). Firstly, the results showed that increased liver weight is associated with higher glucose uptake leading to greater lipid synthesis. Secondly, this increase is probably also due to a decline in the level of export of triglycerides and cholesterol from the liver by maintaining them at high hepatic concentration levels. Finally, the increase in liver weight could lead to a significant decrease in the efficiency of aerobic energy metabolism associated with a significant increase in the level of oxidative stress.
Published: 2021

30. Integrative biology defines novel biomarkers of resistance to strongylid infection in horses

Author: Mickaël Riou, Cécile Canlet, Alexandra Blanchard, Núria Mach, Guillaume Sallé, Christine Koch, Fabrice Reigner, Joshua Malsa, Jacques Cortet, Noémie Perrot, Infectiologie et Santé Publique (UMR ISP), Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-ToxAlim (ToxAlim), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Unité Expérimentale de Physiologie Animale de l‘Orfrasiére (UE PAO), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Plateforme d'Infectiologie Expérimentale (PFIE), Pancosma, Génétique Animale et Biologie Intégrative (GABI), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), INRAE, grant of Institut Français du Cheval et de l’Équitation, Université de Tours-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-ToxAlim (ToxAlim), Université Paris-Saclay-AgroParisTech-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse)
Subjects: Drug, Parasitic infection, Magnetic Resonance Spectroscopy, Nematoda, Science, Phenylalanine, media_common.quotation_subject, Biology, Article, Blood cell, Feces, 03 medical and health sciences, Drug treatment, 0302 clinical medicine, medicine, Prevotella, Animals, Metabolomics, Integrative biology, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Horses, Anthelmintic, Phenylalanine level, Parasite Egg Count, 030304 developmental biology, media_common, Anthelmintics, 2. Zero hunger, 0303 health sciences, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, 3-Hydroxybutyric Acid, Resistance (ecology), Discriminant Analysis, Diagnostic markers, biology.organism_classification, 3. Good health, medicine.anatomical_structure, Immunology, Medicine, Horse Diseases, Seasons, Systems biology, Biomarkers, 030217 neurology & neurosurgery, medicine.drug
Abstract: International audience; The widespread failure of anthelmintic drugs against nematodes of veterinary interest requires novel control strategies. Selective treatment of the most susceptible individuals could reduce drug selection pressure but requires appropriate biomarkers of the intrinsic susceptibility potential. To date, this has been missing in livestock species. Here, we selected Welsh ponies with divergent intrinsic susceptibility (measured by their egg excretion levels) to cyathostomin infection and found that their divergence was sustained across a 10-year time window. Using this unique set of individuals, we monitored variations in their blood cell populations, plasma metabolites and faecal microbiota over a grazing season to isolate core differences between their respective responses under worm-free or natural infection conditions. Our analyses identified the concomitant rise in plasma phenylalanine level and faecal Prevotella abundance and the reduction in circulating monocyte counts as biomarkers of the need for drug treatment (egg excretion above 200 eggs/g). This biological signal was replicated in other independent populations. We also unravelled an immunometabolic network encompassing plasma beta-hydroxybutyrate level, short-chain fatty acid producing bacteria and circulating neutrophils that forms the discriminant baseline between susceptible and resistant individuals. Altogether our observations open new perspectives on the susceptibility of equids to strongylid infection and leave scope for both new biomarkers of infection and nutritional intervention.
Published: 2021

31. Identification of Plasmatic Biomarkers of

Author: Zohre, Mozduri, Nathalie, Marty-Gasset, Bara, Lo, Ali Akbar, Masoudi, Mireille, Morisson, Cécile, Canlet, Julien, Arroyo, Agnès, Bonnet, and Cécile M D, Bonnefont
Subjects: Physiology, quality, biomarker, foie gras, liver, metabolomics, plasma, Original Research
Abstract: The foie gras is an emblematic product of French gastronomy composed of waterfowl fatty liver. The organoleptic qualities of this product depend on the liver characteristics such as liver weight (LW) and technological yield (TY) at cooking. One of the main issues for producers is to classify the foie gras with high or low technological quality before cooking them. Thus the study aims at identifying biomarkers of these characteristics with non-invasive biomarkers in duck. 1H-NMR (nuclear magnetic resonance of the proton) analyses were performed on plasma of male mule ducks at different time points during the overfeeding period to obtain a large range of liver characteristics so as to identify plasmatic biomarkers of foie gras. We used two methods, one based on bucket data from the 1H-NMR spectra and another one based on the fingerprints of several metabolites. PLS analyses and Linear models were performed to identify biomarkers. We identified 18 biomarkers of liver weight and 15 biomarkers of technological yield. As these two quality parameters were strongly correlated (−0.82), 13 biomarkers were common. The lactate was the most important biomarker, the other were mainly amino acids. Contrary to the amino acids, the lactate increased with the liver weight and decreased with the technological yield. We also identified 5 biomarkers specific to LW (3 carbohydrates: glucuronic acid, mannose, sorbitol and 2 amino acids: glutamic acid and methionine) that were negatively correlated to liver weight. It was of main interest to identify 2 biomarkers specific to the technological yield. Contrary to the isovaleric acid, the valine was negatively correlated to the technological yield.
Published: 2020

32. Metabolomic signatures in elite cyclists: differential characterization of a seeming normal endocrine status regarding three serum hormones

Author: François-Xavier Lejeune, Alain Paris, Jean-Christophe Thalabard, Jérôme Molina, Boris Labrador, Michel Guinot, Michel Rieu, Cécile Canlet, Yves Le Bouc, Armand Mégret, Molécules de Communication et Adaptation des Micro-organismes (MCAM), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre] (IM2A), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-ToxAlim (ToxAlim), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Dynamiques et écologie des paysages agriforestiers (DYNAFOR), École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National Polytechnique (Toulouse) (Toulouse INP), Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Hypoxie : Physiopathologie Respiratoire et Cardiovasculaire (HP2), Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM), FFC, Agence Française de Lutte contre le Dopage (AFLD), Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), French Agency for Doping Control (AFLD) R09223DD, World Anti-Doping Agency (WADA): 006D1442, R07157DD, AFLD, WADA, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Sorbonne Université (SU), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-ToxAlim (ToxAlim), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), PARIS, Alain, Metatoul AXIOM (E20 ), MetaboHUB-MetaToul, and Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Subjects: Magnetic Resonance Spectroscopy, SDA, Hydrocortisone, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Physiology, Context (language use), Biology, 01 natural sciences, Biochemistry, Cortisol, 03 medical and health sciences, 0302 clinical medicine, Metabolomics, Doping, Endocrine system, Humans, Testosterone, IGF1, 010401 analytical chemistry, 030229 sport sciences, Linear discriminant analysis, [STAT] Statistics [stat], 0104 chemical sciences, Diet, [SDV] Life Sciences [q-bio], [STAT]Statistics [stat], Sample size determination, Cohort, Hormone
Abstract: International audience; • IntroductionSerum phenotyping of elite cyclists regarding cortisol, IGF1 and testosterone is a way to detect endocrine disruptions possibly explained by exercise overload, non-balanced diet or by doping. This latter disruption-driven approach is supported by fundamental physiology although without any evidence of any metabolic markers. • ObjectivesSerum samples were distributed through Low, High or Normal endocrine classes according to hormone concentration. A 1H NMR metabolomic study of 655 serum obtained in the context of the longitudinal medical follow-up of 253 subjects was performed to discriminate the three classes for every endocrine phenotype.• MethodsAn original processing algorithm was built which combined a partial-least squares-based orthogonal correction of metabolomic signals and a shrinkage discriminant analysis (SDA) to get satisfying classifications. An extended validation procedure was used to plan in larger size cohorts a minimal size to get a global prediction rate (GPR), i.e. the product of the three class prediction rates, higher than 99.9%.• ResultsConsidering the 200 most SDA-informative variables, a sigmoidal fitting of the GPR gave estimates of a minimal sample size to 929, 2346 and 1408 for cortisol, IGF1 and testosterone, respectively. Analysis of outliers from cortisol and testosterone Normal classes outside the 97.5%-confidence limit of score prediction revealed possibly i) an inadequate protein intake for outliers or ii) an intake of dietary ergogenics, glycine or glutamine, which might explain the significant presence of heterogeneous metabolic profiles in a supposedly normal cyclists subgroup. • ConclusionIn a next validation metabolomics study of a so-sized cohort, anthropological, clinical and dietary metadata should be recorded in priority at the blood collection time to confirm these functional hypotheses.
Published: 2020

33. Perinatal exposure to a dietary pesticide cocktail does not increase susceptibility to high-fat diet-induced metabolic perturbations at adulthood but modifies urinary and fecal metabolic fingerprints in C57Bl6/J mice

Author: Wendy Klement, Hervé Guillou, Léonie Dopavogui, Lorraine Smith, Laurence Gamet-Payrastre, Guylène Feuillet, Nicola Marchi, Arnaud Polizzi, Frédéric de Bock, Emilien L. Jamin, Laurent Debrauwer, Sandrine Ellero-Simatos, Céline Lukowicz, Benoist Schaal, Sharon Barretto, Nicolas Loiseau, Bruno Patris, Cécile Canlet, Laila Mselli-Lakhal, Frédéric Lasserre, Anne Fougerat, Colette Denis, Toxicologie Intégrative & Métabolisme (ToxAlim-TIM), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-ToxAlim (ToxAlim), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Exposition, Perturbation Endocrino-métabolique et Reproduction (ToxAlim-EXPER), L.S. PhD is supported by grants from the Ministry for Agriculture and Food and the Ministry for an Ecological and Solidary Transition, with the financial support of the French Biodiversity Agency and from the department AlimH of INRAE. This work was supported by a grant from the Ministry for Agriculture and Food and the Ministry for an Ecological and Solidary Transition, with the financial support of the French Biodiversity Agency (Epidemicmac and GepeTho), by ANR, France (Syneract and Hepatobrain) and Region Occitanie. We thank Anexplo Genotoul MetaToul for their excellent work on plasma biochemistry. All MS and NMR experiments were performed using instruments of the Metatoul-AXIOM platform, partner of the national infrastructure of metabolomics and fluxomics: MetaboHUB [MetaboHUB-ANR-11-INBS-0010, 2011], ANR-11-INBS-0010,METABOHUB,Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation(2011), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Metatoul AXIOM (E20 ), MetaboHUB-MetaToul, Guerineau, Nathalie C., and Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation - - METABOHUB2011 - ANR-11-INBS-0010 - INBS - VALID
Subjects: Tolerable daily intake, 010504 meteorology & atmospheric sciences, [SDV]Life Sciences [q-bio], Physiology, Urine, 010501 environmental sciences, Perinatal, Diet, High-Fat, 01 natural sciences, Energy homeostasis, Dietary exposure, chemistry.chemical_compound, Feces, Mice, Lactation, Medicine, Animals, Metabolomics, Pesticides, lcsh:Environmental sciences, Captan, 0105 earth and related environmental sciences, General Environmental Science, lcsh:GE1-350, 2. Zero hunger, Perinatal Exposure, business.industry, Pesticide, Pesticide cocktail, Gastrointestinal Microbiome, [SDV] Life Sciences [q-bio], Mice, Inbred C57BL, medicine.anatomical_structure, Metabolism, chemistry, 13. Climate action, Female, business
Abstract: International audience; Background: We recently demonstrated that chronic dietary exposure to a mixture of pesticides at low-doses induced sexually dimorphic obesogenic and diabetogenic effects in adult mice. Perinatal pesticide exposure may also be a factor in metabolic disease etiology. However, the long-term consequences of perinatal pesticide exposure remain controversial and largely unexplored.Objectives: Here we assessed how perinatal exposure to the same low-dose pesticide cocktail impacted metabolic homeostasis in adult mice.Methods: Six pesticides (boscalid, captan, chlopyrifos, thiachloprid, thiophanate, and ziram) were incorporated in food pellets. During the gestation and lactation periods, female (F0) mice were fed either a pesticide-free or a pesticide-enriched diet at doses exposing them to the tolerable daily intake (TDI) level for each compound, using a 1:1 body weight scaling from humans to mice. All male and female offsprings (F1) were then fed the pesticide-free diet until 18 weeks of age, followed by challenge with a pesticide-free high-fat diet (HFD) for 6 weeks. Metabolic parameters, including body weight, food and water consumption, glucose tolerance, and urinary and fecal metabolomes, were assessed over time. At the end of the experiment, we evaluated energetic metabolism and microbiota activity using biochemical assays, gene expression profiling, and 1H NMR-based metabolomics in the liver, urine, and feces.Results: Perinatal pesticide exposure did not affect body weight or energy homeostasis in 6- and 14-week-old mice. As expected, HFD increased body weight and induced metabolic disorders as compared to a low-fat diet. However, HFD-induced metabolic perturbations were similar between mice with and without perinatal pesticide exposure. Interestingly, perinatal pesticide exposure induced time-specific and sex-specific alterations in the urinary and fecal metabolomes of adult mice, suggesting long-lasting changes in gut microbiota.Conclusions: Perinatal pesticide exposure induced sustained sexually dimorphic perturbations of the urinary and fecal metabolic fingerprints, but did not significantly influence the development of HFD-induced metabolic diseases.
Published: 2020

34. Joint automatic metabolite identification and quantification of a set of 1H NMR spectra

Author: Gaëlle Lefort, Cécile Canlet, Laurence Liaubet, Nathalie Marty-Gasset, Rémi Servien, Nathalie Vialaneix, Unité de Mathématiques et Informatique Appliquées de Toulouse (MIAT INRA), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire de Biotechnologie de l'Environnement [Narbonne] (LBE), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Innovations Thérapeutiques et Résistances (InTheRes), SubPig project funded by INRAE metaprogram fund GISA, ANR-16-CONV-0004,DIGITAG,Institut Convergences en Agriculture Numérique(2016), ToxAlim (ToxAlim), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), and Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier SupAgro
Subjects: Computer science, Metabolite, 010402 general chemistry, 01 natural sciences, Spectral line, Analytical Chemistry, Set (abstract data type), 03 medical and health sciences, chemistry.chemical_compound, Metabolomics, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, [MATH.MATH-ST]Mathematics [math]/Statistics [math.ST], Metabolome, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], 030304 developmental biology, [STAT.AP]Statistics [stat]/Applications [stat.AP], 0303 health sciences, business.industry, 010401 analytical chemistry, Pattern recognition, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 0104 chemical sciences, Identification (information), chemistry, Proton NMR, Biomarker (medicine), Artificial intelligence, Joint (audio engineering), business, Biological system, [CHIM.CHEM]Chemical Sciences/Cheminformatics
Abstract: Metabolomics is a promising approach to characterize phenotypes or to identify biomarkers. It is also easily accessible through NMR, which can provide a comprehensive understanding of the metabolome of any living organisms. However, the analysis of 1H NMR spectrum remains difficult, mainly due to the different problems encountered to perform automatic identification and quantification of metabolites in a reproducible way. In addition, methods that perform automatic identification and quantification of metabolites often do it for one given complex mixture spectrum. Hence, when a set of complex mixture spectra coming from the same experiment has to be processed, the approach is simply repeated independently for every spectrum, despite their resemblance. Here, we present a new method that is the first to identify and quantify metabolites by integrating information coming from several complex spectra of the same experiment. The performances of this new method are then evaluated on both simulated and real datasets. The results show an improvement in the metabolite identification and in the accuracy of metabolite quantifications, especially when the concentration is low. This joint procedure is available in version 2.0 of ASICS package.
Published: 2020

35. Transgenerational metabolic disorders and reproduction defects induced by benzo[a]pyrene in Xenopus tropicalis

Author: Sophie Sroda, Marie Usal, Sylvie Veyrenc, Marie Tremblay-Franco, Jean-Baptiste Fini, Muriel Raveton, Christophe Regnault, Marie Darracq--Ghitalla-Ciock, Cécile Canlet, Stéphane Reynaud, Laboratoire d'Ecologie Alpine (LECA ), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Physiologie moléculaire et adaptation (PhyMA), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-ToxAlim (ToxAlim), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-ToxAlim (ToxAlim), Metatoul AXIOM (E20 ), MetaboHUB-MetaToul, ToxAlim (ToxAlim), and CCSD, Accord Elsevier
Subjects: [SDE] Environmental Sciences, medicine.medical_specialty, 010504 meteorology & atmospheric sciences, Health, Toxicology and Mutagenesis, Metabolite, media_common.quotation_subject, Xenopus, Population, 010501 environmental sciences, Biology, Endocrine Disruptors, Toxicology, 01 natural sciences, chemistry.chemical_compound, Metabolic Diseases, Internal medicine, medicine, Benzo(a)pyrene, Sexual maturity, Animals, Humans, Xenopus tropicalis, Metamorphosis, education, 0105 earth and related environmental sciences, media_common, education.field_of_study, Reproduction, Fatty liver, General Medicine, medicine.disease, biology.organism_classification, Pollution, Metabolic syndrome, Endocrinology, chemistry, Endocrine disruptor, Amphibian population decline, [SDE]Environmental Sciences, Female, Transgenerational
Abstract: International audience; Metabolic disorders induced by endocrine disruptors (ED) may contribute to amphibian population declines but no transgenerational studies have evaluated this hypothesis. Here we show that Xenopus tropicalis, exposed from the tadpole stage, to the ED benzo[a]pyrene (BaP, 50 ng.L−1) produced F2 progeny with delayed metamorphosis and sexual maturity. At the adult stage, F2–BaP females displayed fatty liver with inflammation, tissue disorganization and metabolomic and transcriptomic signatures typical of nonalcoholic steato-hepatitis (NASH). This phenotype, similar to that observed in F0 and F1 females, was accompanied by a pancreatic insulin secretory defect. Metabolic disrupted F2–BaP females laid eggs with metabolite contents significantly different from the control and these eggs did not produce viable progeny. This study demonstrated that an ED can induce transgenerational disruption of metabolism and population collapse in amphibians under laboratory conditions. These results show that ED benzo[a]pyrene can impact metabolism over multiple generations and support epidemiological studies implicating environmental EDs in metabolic diseases in humans.
Published: 2020

36. Postprandial NMR-Based Metabolic Exchanges Reflect Impaired Phenotypic Flexibility across Splanchnic Organs in the Obese Yucatan Mini-Pig

Author: Isabelle Savary-Auzeloux, Cécile Canlet, Nathalie Poupin, Dominique Dardevet, Marie Tremblay-Franco, Aurélien Amiel, Fabien Jourdan, Sergio Polakof, Laurent Debrauwer, Didier Rémond, Metatoul AXIOM (E20 ), MetaboHUB-MetaToul, MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-ToxAlim (ToxAlim), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MetaToul FluxoMet (TBI-MetaToul), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Toulouse Biotechnology Institute (TBI), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Métabolisme et Xénobiotiques (ToxAlim-MeX), ToxAlim (ToxAlim), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Unité de Nutrition Humaine (UNH), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), INRAE AlimH department funding French Infrastructure for Metabolomics and Fluxomics MetaboHUB-ANR-11-INBS-0010, Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-ToxAlim (ToxAlim), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Métabolomique et Fluxomique (MetaToul) (TBI-MetaToul), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Biotechnology Institute (TBI), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3)
Subjects: 0301 basic medicine, Blood Glucose, Magnetic Resonance Spectroscopy, Swine, high fat-high sucrose diet, [SDV]Life Sciences [q-bio], postprandial, mini-pigs, chemistry.chemical_compound, 0302 clinical medicine, Dietary Sucrose, energy metabolism, Glucose homeostasis, Homeostasis, Intestinal Mucosa, Nutrition and Dietetics, Glycogen, Postprandial Period, metabolomics, Postprandial, Swine, Miniature, Animal Nutritional Physiological Phenomena, Female, Splanchnic, lcsh:Nutrition. Foods and food supply, arteriovenous differences, medicine.medical_specialty, 030209 endocrinology & metabolism, lcsh:TX341-641, Biology, Diet, High-Fat, liver, Article, 03 medical and health sciences, Metabolomics, Insulin resistance, Internal medicine, medicine, Metabolome, Animals, Obesity, intestine, phenotypic flexibility, medicine.disease, 030104 developmental biology, Endocrinology, chemistry, Insulin Resistance, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Food Science
Abstract: The postprandial period represents one of the most challenging phenomena in whole-body metabolism, and it can be used as a unique window to evaluate the phenotypic flexibility of an individual in response to a given meal, which can be done by measuring the resilience of the metabolome. However, this exploration of the metabolism has never been applied to the arteriovenous (AV) exploration of organs metabolism. Here, we applied an AV metabolomics strategy to evaluate the postprandial flexibility across the liver and the intestine of mini-pigs subjected to a high fat&ndash, high sucrose (HFHS) diet for 2 months. We identified for the first time a postprandial signature associated to the insulin resistance and obesity outcomes, and we showed that the splanchnic postprandial metabolome was considerably affected by the meal and the obesity condition. Most of the changes induced by obesity were observed in the exchanges across the liver, where the metabolism was reorganized to maintain whole body glucose homeostasis by routing glucose formed de novo from a large variety of substrates into glycogen. Furthermore, metabolites related to lipid handling and energy metabolism showed a blunted postprandial response in the obese animals across organs. Finally, some of our results reflect a loss of flexibility in response to the HFHS meal challenge in unsuspected metabolic pathways that must be further explored as potential new events involved in early obesity and the onset of insulin resistance.
Published: 2020

37. Functional maturation of the gut microbiota at weaning is influenced by maternal environment in piglets

Author: Olivier Zemb, Céline Barilly, Lisa F. Gill, Laurent Cauquil, Géraldine Pascal, Cécile Canlet, Sylvie Combes, Allan Bertide, Ingrid Ahn, Arnaud Samsom, and Martin Beaumont
Subjects: Animal science, fluids and secretions, Ruminococcus, Lactobacillus, animal diseases, Weaning, Microbiome, Biology, Gut flora, biology.organism_classification, Relative species abundance, Feces, Ruminococcaceae
Abstract: SUMMARYThe objective of this study was to analyze in piglets the impact of weaning on the production of metabolites by gut bacteria and to determine whether early life environment influences the functional maturation of the gut microbiota. Fecal metabolome and microbiome were analyzed in piglets raised in two separate maternity farms and mixed at weaning. In piglets from both maternity farms, the relative abundance ofLactobacillusand of the predicted function “Fucose degradation” decreased after weaning while the relative abundance ofRuminococcus 2and of the predicted function “Starch degradation” increased. In piglets from the first maternity farm, the relative concentration of biogenic amines and the relative abundance ofEscherichi-Shigelladecreased after weaning while the relative concentration of short chain fatty acids and the relative abundance ofChristensenellaceae R-7 groupandRuminococcaceae UCG-002increased. These changes were not observed at weaning in piglets from the second maternity farm probably because they already had high relative concentration of short chain fatty acids and higher relative abundance ofChristensenellaceae R-7 groupandRuminococcaceae UCG-002during the suckling period. In conclusion, the functional maturation of the microbiota at weaning is highly dependent on the maternal environment in piglets.ORIGINALITY - SIGNIFICANCE STATEMENTBacterial metabolites are key molecular intermediates between the gut microbiota and host cells. Our study in piglets reveals that the metabolic activity of the gut microbiota shifts at weaning, a key developmental period for intestinal and immune health. We also show that this functional maturation of the gut microbiota is strongly influenced by maternal environment. Thus, targeting early life environmental factors is a promising strategy to program health trough the production of beneficial bacterial metabolites at the suckling-to-weaning transition.
Published: 2020
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38. The maturity in fetal pigs using a multi-fluid metabolomic approach

Author: Cécile Canlet, Nathalie Vialaneix, Alain Paris, Hélène Quesnel, Gaëlle Lefort, Laurianne Canario, Rémi Servien, Laurence Liaubet, Nathalie Iannuccelli, Yvon Billon, Unité de Mathématiques et Informatique Appliquées de Toulouse (MIAT INRA), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire de Biotechnologie de l'Environnement [Narbonne] (LBE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier SupAgro, Innovations Thérapeutiques et Résistances (InTheRes), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Physiologie, Environnement et Génétique pour l'Animal et les Systèmes d'Elevage [Rennes] (PEGASE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-INSTITUT AGRO Agrocampus Ouest, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Unité Expérimentale Elevages Porcins Innovants (GenESI), Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-ToxAlim (ToxAlim), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Molécules de Communication et Adaptation des Micro-organismes (MCAM), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), INRAE Mathematics and Computer Science Division, by INRAE Animal Genetics Division and by INRAE Animal Health Divison, ANR-09-GENM-0005,PORCINET,Approche intégrée de la maturité des porcelets(2009), ANR-16-CONV-0004,DIGITAG,Institut Convergences en Agriculture Numérique(2016), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), AGROCAMPUS OUEST, Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse)
Subjects: Litter (animal), Amniotic fluid, Litter Size, Swine, lcsh:Medicine, Physiology, Reproductive biology, Biology, Article, Fetal Development, 03 medical and health sciences, Metabolomics, Fetus, Pregnancy, Metabolome, Weaning, Animals, lcsh:Science, 030304 developmental biology, 2. Zero hunger, 0303 health sciences, [STAT.AP]Statistics [stat]/Applications [stat.AP], [SDV.BA]Life Sciences [q-bio]/Animal biology, lcsh:R, 0402 animal and dairy science, 04 agricultural and veterinary sciences, Intrauterine growth, 040201 dairy & animal science, Maturity (finance), Phenotype, Animals, Newborn, Gestation, lcsh:Q, Female
Abstract: In mammalian species, the first days after birth are an important period for survival and the rates of mortality before weaning are high. In pigs, the perinatal deaths average 20% of the litter, with important economic and societal consequences. Among the factors influencing piglet survival at birth, the maturity is likely to be one of the most important. Maturity can be defined as the outcome of complex mechanisms of intra-uterine development and maturation occurring during the last month of gestation. Here, we provide new insights on maturity by studying the end of gestation at two different stages (three weeks before term and close to term) in two breeds of pigs that strongly differ in terms of neonatal survival. Since metabolomics is a promising approach for phenotype characterization or biomarker discovery, we provide a complete understanding of the metabolome of the fetuses in late gestation in three fluids (plasma, urine, and amniotic fluid). We found that biological processes related to amino acid and carbohy-drate metabolisms are critical for piglet maturity. We also confirmed some previously described metabolites associated with delayed growth (e.g., proline and myo-inositol). Altogether, our study proposes new routes for a better characterization of piglet maturity at birth.
Published: 2020
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39. 1H-NMR metabolomics response to a realistic diet contamination with the mycotoxin deoxynivalenol: Effect of probiotics supplementation

Author: Mathieu Castex, Marie Tremblay-Franco, Caroline Achard, Philippe Pinton, Ana Paula Frederico Rodrigues Loureiro Bracarense, Fabien Jourdan, Anne Marie Cossalter, Cécile Canlet, Imourana Alassane-Kpembi, Maxime Chalzaviel, Sylvie Combes, Isabelle P. Oswald, ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université d'Abomey-Calavi, University of Abomey Calavi (UAC), Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-ToxAlim (ToxAlim), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Métabolisme et Xénobiotiques (ToxAlim-MeX), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), MedDay Pharmaceuticals, Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), Plateforme Ezop (Ezop), Lallemand S.A.S., Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Lab. Patologia Animal, and State University of Londrina = Universidade Estadual de Londrina
Subjects: pig, Biology, Toxicology, law.invention, histology, 03 medical and health sciences, chemistry.chemical_compound, Probiotic, 0404 agricultural biotechnology, Metabolomics, law, mycotoxins, Metabolome, Food science, Mycotoxin, intestine, 030304 developmental biology, Subclinical infection, 2. Zero hunger, 0303 health sciences, Saccharomyces cerevisiae boulardii, 04 agricultural and veterinary sciences, General Medicine, Metabolism, 040401 food science, metabolomics, Yeast, 3. Good health, chemistry, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Toxicity, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Food Science
Abstract: International audience; Low-level contamination of food and feed by deoxynivalenol (DON) is unavoidable. We investigated the effects of subclinical treatment with DON, and supplementation with probiotic yeast Saccharomyces cerevisiae boulardii I1079 as a preventive strategy in piglets. Thirty-six animals were randomly assigned to either a control diet, a diet contaminated with DON (3 mg/kg), a diet supplemented with yeast (4 × 109 CFU/kg), or a DON-contaminated diet supplemented with yeast, for four weeks. Plasma and tissue samples were collected for biochemical analysis, 1H-NMR untargeted metabolomics, and histology. DON induced no significant modifications in biochemical parameters. However, lesion scores were higher and metabolomics highlighted alterations of amino acid and 2-oxocarboxylic acid metabolism. Administering yeast affected aminoacyl-tRNA synthesis and amino acid and glycerophospholipid metabolism. Yeast supplementation of piglets exposed to DON prevented histological alterations, and partial least square discriminant analysis emphasised similarity between the metabolic profiles of their plasma and that of the control group. The effect on liver metabolome remained marginal, indicating that the toxicity of the mycotoxin was not eliminated. These findings show that the 1H-NMR metabolomics profile is a reliable biomarker to assess subclinical exposure to DON, and that supplementation with S. cerevisiae boulardii increases the resilience of piglets to this mycotoxin.
Published: 2020

40. Proton NMR enables the absolute quantification of aqueous metabolites and lipid classes in unique mouse liver samples

Author: Aurélien Amiel, Hervé Guillou, Marie Tremblay-Franco, Simon Ducheix, Roselyne Gautier, Alexandra Montagner, Laurent Debrauwer, Arnaud Polizzi, Justine Bertrand-Michel, Cécile Canlet, ProdInra, Migration, ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), National Infrastructure for Metabolomics and Fluxomics, Metatoul AXIOM (E20 ), MetaboHUB-MetaToul, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-ToxAlim (ToxAlim), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Toxicologie Intégrative & Métabolisme (ToxAlim-TIM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Institut National de la Santé et de la Recherche Médicale (INSERM), Plateau MetaToul-LIPIDOMIQUE = MetaToul-Lipidomics, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-MetaboHUB-MetaToul, Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Région Occitanie (H.G., A.P., A.M., S.D.), ANR Hepadialogue ANR-17-CE14-0015 (H.G., A.P., A.M., S.D.), and the French National Infrastructure for Metabolomics and Fluxomics MetaboHUB ANR-11-INBS-010 (C.C., A.A., L.D., M.T.-F., R.G., J.B.-M.), Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), MetaToul-MetaboHUB, Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-MetaToul-MetaboHUB, Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), and Canlet, Cécile
Subjects: 0301 basic medicine, Endocrinology, Diabetes and Metabolism, Metabolite, 1H-NMR spectroscopy, Toxicology, liver, 01 natural sciences, Biochemistry, Article, 03 medical and health sciences, chemistry.chemical_compound, Lipidomics, medicine, steatosis, Food and Nutrition, Molecular Biology, Toxicologie, Alanine, Aqueous solution, Chromatography, Cholesterol, 010401 analytical chemistry, Extraction (chemistry), metabolomics quantitative profiling, medicine.disease, 0104 chemical sciences, [SDV.TOX] Life Sciences [q-bio]/Toxicology, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, 030104 developmental biology, chemistry, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Alimentation et Nutrition, Proton NMR, lipidomics, Steatosis, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: International audience; Hepatic metabolites provide valuable information on the physiological state of an organism, and thus, they are monitored in many clinical situations. Typically, monitoring requires several analyses for each class of targeted metabolite, which is time consuming. The present study aimed to evaluate a proton nuclear magnetic resonance (1H-NMR) method for obtaining quantitative measurements of aqueous and lipidic metabolites. We optimized the extraction protocol, the standard samples, and the organic solvents for the absolute quantification of lipid species. To validate the method, we analyzed metabolic profiles in livers of mice fed three different diets. We compared our results with values obtained with conventional methods and found strong correlations. The 1H-NMR protocol enabled the absolute quantification of 29 aqueous metabolites and eight lipid classes. Results showed that mice fed a diet enriched in saturated fatty acids had higher levels of triglycerides, cholesterol ester, monounsaturated fatty acids, lactate, 3-hydroxy-butyrate, and alanine and lower levels of glucose, compared to mice fed a control diet. In conclusion, proton NMR provided a rapid overview of the main lipid classes (triglycerides, cholesterol, phospholipids, fatty acids) and the most abundant aqueous metabolites in liver.
Published: 2020

41. Create, run, share, publish, and reference your LC–MS, FIA–MS, GC–MS, and NMR data analysis workflows with the Workflow4Metabolomics 3.0 Galaxy online infrastructure for metabolomics

Author: Cécile Canlet, Franck Giacomoni, Sophie Goulitquer, Jean-François Martin, Patrick Tardivel, Rémi Servien, Etienne A. Thévenot, Alexis Delabrière, Marie Tremblay-Franco, Yann Guitton, Mélanie Pétéra, Gildas Le Corguillé, Christophe Duperier, Pierrick Roger-Mele, Christophe Caron, Misharl Monsoor, Laboratoire d'étude des Résidus et Contaminants dans les Aliments (LABERCA), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Institut de Recherche en Génie Civil et Mécanique (GeM), Université de Nantes - Faculté des Sciences et des Techniques, Université de Nantes (UN)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), ABiMS - Informatique et bioinformatique = Analysis and Bioinformatics for Marine Science (FR2424), Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Plateforme d'Exploration du Métbolisme, MetaboHUB, Laboratoire d'analyse des données et d'intelligence des systèmes (LADIS), Département Métrologie Instrumentation & Information (DM2I), Laboratoire d'Intégration des Systèmes et des Technologies (LIST), Université Paris-Saclay-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Laboratoire d'Intégration des Systèmes et des Technologies (LIST), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (LUBEM), Ingenum, Institut National de la Recherche Agronomique (INRA), ANR-11-INBS-0013/11-INBS-0013,ReNaBi-IFB,Institut français de bioinformatique(2011), ANR-11-INBS-0010/11-INBS-0010,METABOHUB,Développement d’une infrastructure française distribuée pour la métabolomique dédiée à l’innovation(2011), ANR-10-BTBR-04-01/10-BTBR-0004,IDEALG,IDEALG(2010), Institut National de la Recherche Agronomique (INRA)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), MetaToul AXIOM (E20), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-MetaboHUB-MetaToul, MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), ABiMS - Informatique et bioinformatique = Analysis and Bioinformatics for Marine Science (ABIMS), Fédération de recherche de Roscoff (FR2424), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Station biologique de Roscoff (SBR), Plateforme Exploration du Métabolisme (PFEM), MetaboHUB-Clermont, MetaboHUB-MetaboHUB-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Laboratoire d'Intégration des Systèmes et des Technologies (LIST (CEA)), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Laboratoire d'Intégration des Systèmes et des Technologies (LIST (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Université de Toulouse (UT)-Université de Toulouse (UT), Laboratoire Sciences des Données et de la Décision (LS2D), French Institute of Bioinformatics (IFB) ANR-11-INBS-0013, French Infrastructure for Metabolomics and Fluxomics (MetaboHUB) ANR-11-INBS-0010, IDEALG project ANR-10-BTBR-04, ANR-11-INBS-0013,IFB (ex Renabi-IFB),Institut français de bioinformatique(2011), ANR-11-INBS-0010,METABOHUB,Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation(2011), ANR-10-BTBR-0004,IDEALG,Biotechnologies pour la valorisation des macroalgues(2010), Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Laboratoire d'Intégration des Systèmes et des Technologies (LIST), Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: MASS SPECTROMETRY, 0301 basic medicine, Web server, Magnetic Resonance Spectroscopy, Computer science, Data analysis, CHROMATOGRAPHY, spectrum analysis, Bioinformatics, computer.software_genre, Quantitative Biology - Quantitative Methods, Biochemistry, Workflow, 03 medical and health sciences, Annotation, Resource (project management), [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Digital Object Identifier, Animals, Humans, Metabolomics, [INFO.INFO-DL]Computer Science [cs]/Digital Libraries [cs.DL], Preprocessor, signal processing, Quantitative Methods (q-bio.QM), Electronic Data Processing, ADULT URINARY METABOLOME, IDENTIFICATION, BIOINFORMATICS, MASS-SPECTROMETRY, Cell Biology, COMPUTATIONAL METABOLOMICS, Data science, GENOME, Galaxy, Identification (information), 030104 developmental biology, FOS: Biological sciences, WEB SERVER, E-infrastructure, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], computer, Software, REPOSITORY, STANDARDS
Abstract: Metabolomics is a key approach in modern functional genomics and systems biology. Due to the complexity of metabolomics data, the variety of experimental designs, and the variety of existing bioinformatics tools, providing experimenters with a simple and efficient resource to conduct comprehensive and rigorous analysis of their data is of utmost importance. In 2014, we launched the Workflow4Metabolomics (W4M, http://workflow4metabolomics.org) online infrastructure for metabolomics built on the Galaxy environment, which offers user-friendly features to build and run data analysis workflows including preprocessing, statistical analysis, and annotation steps. Here we present the new W4M 3.0 release, which contains twice as many tools as the first version, and provides two features which are, to our knowledge, unique among online resources. First, data from the four major metabolomics technologies (i.e., LC-MS, FIA-MS, GC-MS, and NMR) can be analyzed on a single platform. By using three studies in human physiology, alga evolution, and animal toxicology, we demonstrate how the 40 available tools can be easily combined to address biological issues. Second, the full analysis (including the workflow, the parameter values, the input data and output results) can be referenced with a permanent digital object identifier (DOI). Publication of data analyses is of major importance for robust and reproducible science. Furthermore, the publicly shared workflows are of high-value for e-learning and training. The Workflow4Metabolomics 3.0 e-infrastructure thus not only offers a unique online environment for analysis of data from the main metabolomics technologies, but it is also the first reference repository for metabolomics workflows., The International Journal of Biochemistry \& Cell Biology, Elsevier, 2017
Published: 2017

42. ASICS : identifier et quantifier des métabolites à partir d'un spectre RMN 1H

Author: Gaëlle Lefort, Laurence Liaubet, Cécile Canlet, Nathalie Vialaneix, Rémi Servien, Unité de Mathématiques et Informatique Appliquées de Toulouse (MIAT INRA), Institut National de la Recherche Agronomique (INRA), Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Innovations Thérapeutiques et Résistances (InTheRes), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), ANR-16-CONV-0004, ANR-09-GENM005, Société Française de Statistique (SFdS). FRA., Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-MetaToul-MetaboHUB, Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), and Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: sélection de variables, [SDV.GEN]Life Sciences [q-bio]/Genetics, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, résonance Magnétique Nucléaire (RMN), [SDV]Life Sciences [q-bio], métabolomique, quantification de métabolites, [INFO]Computer Science [cs], [MATH]Mathematics [math]
Abstract: National audience; La résonance magnétique nucléaire du proton (1H-RMN) est une technologie haut-débit permettant d'obtenir des profils métaboliques, sous forme de spectres, à un coût relativement faible. C'est un outil prometteur pour détecter des biomarqueurs facilement mesurables. Cependant, les métabolites présents dans un mélange complexe ne sont pas identifiables et quantifiables directement, ce qui limite l'interprétabilité de ces approches. Pour faciliter l'utilisation de ces données, nous avons développé une méthode d'analyse automatique, encapsulée dans un nouveau package R/Bioconductor, ASICS, qui permet l'identification et la quantification globale et automatique des métabolites dans un spectre RMN. Le package permet d'enchaîner facilement toutes les étapes de l'analyse (pré-traitements, quantification, outils de diagnostic pour juger de la qualité des quantifications, analyses statistiques post-quantification).
Published: 2019

43. Large-Scale Modeling Approach Reveals Functional Metabolic Shifts during Hepatic Differentiation

Author: Anne Corlu, Sandrine Bruel, Nicolas J. Cabaton, Fabien Jourdan, Florence Vinson, Hélène Dubois-Pot-Schneider, Clément Frainay, Cécile Canlet, Daniel Zalko, Elodie Person, Fabrice Morel, Marie-Anne Robin, Florence Maurier, Nathalie Poupin, Bernard Fromenty, Métabolisme et Xénobiotiques (ToxAlim-MeX), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported in part by the French Ministry of Research and the National Research Agency, as part of the French MetaboHUB infrastructure (the National Metabolomics and Fluxomics Infrastructure, Grant ANR-INBS-0010) and the NISTEC project (Grant ANR-09-CESA-003)., ANR-09-CESA-0003,NISTEC,Nouvelles stratégies in vitro pour l'évaluation de la cytotoxicite et la genotoxicite des contaminants de l'environnement(2009), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-MetaToul-MetaboHUB, Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), MetaToul AXIOM (E20), Université de Toulouse (UT)-Université de Toulouse (UT)-MetaboHUB-MetaToul, MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), and Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: 0301 basic medicine, genome-scale metabolic modeling, [SDV]Life Sciences [q-bio], Metabolic network, Network structure, Computational biology, Biology, Models, Biological, Biochemistry, Cell Line, Omics data, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, HepaRG cell line, hepatic differentiation, Humans, Metabolomics, ComputingMilieux_MISCELLANEOUS, transcriptomics and metabolomics, Cell Differentiation, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, General Chemistry, Phenotype, Metabolic pathway, 030104 developmental biology, Cell metabolism, Liver, Flux (metabolism), Metabolic Networks and Pathways, 030217 neurology & neurosurgery, global metabolic shifts
Abstract: International audience; Being able to explore the metabolism of broad metabolizing cells is of critical importance in many research fields. This article presents an original modeling solution combining metabolic network and omics data to identify modulated metabolic pathways and changes in metabolic functions occurring during differentiation of a human hepatic cell line (HepaRG). Our results confirm the activation of hepato-specific functionalities and newly evidence modulation of other metabolic pathways, which could not be evidenced from transcriptomic data alone. Our method takes advantage of the network structure to detect changes in metabolic pathways that do not have gene annotations and exploits flux analyses techniques to identify activated metabolic functions. Compared to the usual cell-specific metabolic network reconstruction approaches, it limits false predictions by considering several possible network configurations to represent one phenotype rather than one arbitrarily selected network. Our approach significantly enhances the comprehensive and functional assessment of cell metabolism, opening further perspectives to investigate metabolic shifts occurring within various biological contexts.
Published: 2019

44. ASICS: an R package for a whole analysis workflow of 1D 1H NMR spectra

Author: Hélène Quesnel, Cécile Canlet, Gaëlle Lefort, Rémi Servien, Marie-Christine Père, Patrick Tardivel, Nathalie Vialaneix, Alain Paris, Laurence Liaubet, Nathalie Iannuccelli, Lefort, Gaëlle, Vialaneix, Nathalie, Servien, Remi, Unité de Mathématiques et Informatique Appliquées de Toulouse (MIAT INRA), Institut National de la Recherche Agronomique (INRA), Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of Wroclaw, Physiologie, Environnement et Génétique pour l'Animal et les Systèmes d'Elevage [Rennes] (PEGASE), Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Molécules de Communication et Adaptation des Micro-organismes (MCAM), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Innovations Thérapeutiques et Résistances (InTheRes), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), ANR-16-CONV-0004,DIGITAG,Institut Convergences en Agriculture Numérique(2016), ANR-09-GENM-0005,PORCINET,Approche intégrée de la maturité des porcelets(2009), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-MetaToul-MetaboHUB, Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and AGROCAMPUS OUEST-Institut National de la Recherche Agronomique (INRA)
Subjects: Statistics and Probability, Magnetic Resonance Spectroscopy, Computer science, Systems biology, Proton Magnetic Resonance Spectroscopy, [SDV]Life Sciences [q-bio], computer.software_genre, 01 natural sciences, Biochemistry, Workflow, Bioconductor, 03 medical and health sciences, Metabolomics, [INFO]Computer Science [cs], [MATH]Mathematics [math], Molecular Biology, 030304 developmental biology, 0303 health sciences, [SDV.GEN]Life Sciences [q-bio]/Genetics, 010401 analytical chemistry, Magnetic Resonance Imaging, 0104 chemical sciences, Computer Science Applications, Computational Mathematics, R package, Metabolic pathway, Identification (information), [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, Computational Theory and Mathematics, Proton NMR, Biomarker (medicine), Data mining, computer, Software
Abstract: Motivation In metabolomics, the detection of new biomarkers from Nuclear Magnetic Resonance (NMR) spectra is a promising approach. However, this analysis remains difficult due to the lack of a whole workflow that handles spectra pre-processing, automatic identification and quantification of metabolites and statistical analyses, in a reproducible way. Results We present ASICS, an R package that contains a complete workflow to analyse spectra from NMR experiments. It contains an automatic approach to identify and quantify metabolites in a complex mixture spectrum and uses the results of the quantification in untargeted and targeted statistical analyses. ASICS was shown to improve the precision of quantification in comparison to existing methods on two independent datasets. In addition, ASICS successfully recovered most metabolites that were found important to explain a two level condition describing the samples by a manual and expert analysis based on bucketing. It also found new relevant metabolites involved in metabolic pathways related to risk factors associated with the condition. Availability and implementation ASICS is distributed as an R package, available on Bioconductor. Supplementary information Supplementary data are available at Bioinformatics online.
Published: 2019

45. Hepatocyte-specific deletion of Pparα promotes NASH in the context of obesity

Author: Arnaud Polizzi, Marie Tremblay-Franco, Frédéric Lasserre, Anne Fougerat, Hervé Guillou, Aurélie Batut, Catherine Postic, Justine Bertrand-Michel, Marion Régnier, Walter Wahli, Edwin Fouché, Nicolas Loiseau, Yannick Lippi, Claire Naylies, Céline Lukowicz, Talal Al Saati, Sandrine Ellero-Simatos, Alexandra Montagner, Dominique Langin, Valentin Barquissau, Cécile Canlet, Sarra Smati, Etienne Mouisel, and Colette Bétoulières
Subjects: chemistry.chemical_classification, medicine.medical_specialty, business.industry, nutritional and metabolic diseases, Fatty acid, Peroxisome proliferator-activated receptor, Inflammation, medicine.disease, Endocrinology, medicine.anatomical_structure, chemistry, Lipid oxidation, Fibrosis, Internal medicine, Hepatocyte, Medicine, Steatohepatitis, medicine.symptom, Steatosis, business
Abstract: ObjectivesPeroxisome proliferator activated receptor α (PPARα) acts as a fatty acid sensor to orchestrate the transcription of genes coding for rate-limiting enzymes required for lipid oxidation in hepatocytes. Mice only lacking Pparα in hepatocytes spontaneously develop steatosis without obesity in aging. Altough steatosis is a benign condition it can develop into non alcoholic steatohepatitis (NASH), which may progress to irreversible damage, such as fibrosis and hepatocarcinoma. While NASH appears as a major public health concern worldwide, it remains an unmet medical need. Several drugs are being tested in clinical trials, including pharmacological agonists for the different PPAR isotypes. In current study, we investigated the role of hepatocyte PPARα in a preclinical model of steatosis.Methods/ResultsWe have investigated the role of hepatocyte PPARα in a preclinical model of steatosis using High Fat Diet (HFD) feeding as a model of obesity in C57BL/6J male Wild-Type mice (WT), in whole-body (Pparα-/-) mice and in mice lacking Pparα in hepatocyte (Pparαhep-/-). We provide evidence that Pparα deletion in hepatocytes promotes NASH in mice fed an HFD. This enhanced NASH susceptibility occurs without development of glucose intolerance. Moreover, our data reveal that non-hepatocytic PPARα activity predominantly contributes to the metabolic response to HFD.ConclusionTaken together, our data support hepatocyte PPARα as being essential to the prevention of steatosis progression to NASH and that extra-hepatocyte PPARα activity contributes to whole-body lipid homeostasis.HighlightsPparα deletion in hepatocytes promotes steatosis and inflammation in HFD-induced obesityHepatocyte-specific deletion of Pparα dissociates NAFLD from glucose intolerance in HFD-induced obesity obesityExtrahepatic PPARα activity contributes to the metabolic response to HFD-induced obesity
Published: 2018

46. Addition of dairy lipids and probiotic Lactobacillus fermentum in infant formula programs gut microbiota and entero-insular axis in adult minipigs

Author: Armelle Cahu, Véronique Romé, Moez Rhimi, Marie Tremblay-Franco, Stéphanie Ferret-Bernard, Philippe Gérard, Cécile Canlet, S. Blat, Isabelle Cuinet, Laurence Le Normand, Samir Dou, Isabelle Nogret, Charlotte Baudry, Isabelle Le Huërou-Luron, Michèle Formal, Pascale Le Ruyet, Marion Lemaire, Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Groupe Lactalis, Physiologie, Environnement et Génétique pour l'Animal et les Systèmes d'Elevage [Rennes] (PEGASE), AGROCAMPUS OUEST-Institut National de la Recherche Agronomique (INRA), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 2014/0580, Association Nationale de la Recherche et de la Technologie (National Association for Research and Technology), The present work received funding from Lactalis Recherche et D&amp, x00E9, veloppement (Retiers, France)., Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-MetaToul-MetaboHUB, Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), MetaToul AXIOM (E20), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-MetaboHUB-MetaToul, MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-MetaboHUB-MetaToul, and ProdInra, Archive Ouverte
Subjects: 0301 basic medicine, Limosilactobacillus fermentum, matière grasse du lait, Swine, [SDV]Life Sciences [q-bio], lcsh:Medicine, microbiote digestif, Gut flora, law.invention, Probiotic, Feces, fluids and secretions, law, nutritional imprinting, Food science, lcsh:Science, ComputingMilieux_MISCELLANEOUS, 2. Zero hunger, chemistry.chemical_classification, milk fat globules, Multidisciplinary, biology, [SDV.BA]Life Sciences [q-bio]/Animal biology, digestive, oral, and skin physiology, probiotique, Lipids, Infant Formula, [SDV] Life Sciences [q-bio], [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, nutrition, Milk, Swine, Miniature, probiotic, Lactobacillus fermentum, digestive system, Article, Clostridia, 03 medical and health sciences, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, fonction endocrine, miniporc, Probiotics, lcsh:R, Fatty acid, Infant, Metabolism, empreinte nutritionnelle, biology.organism_classification, Gastrointestinal Microbiome, 030104 developmental biology, chemistry, Infant formula, barrière épithéliale, Dietary Supplements, Propionate, lcsh:Q, immunité
Abstract: Clinical and animal studies have demonstrated beneficial effects of early consumption of dairy lipids and a probiotic, Lactobacillus fermentum (Lf), on infant gut physiology. The objective of this study was to investigate their long-term effects on gut microbiota and host entero-insular axis and metabolism. Piglets were suckled with a milk formula containing only plant lipids (PL), a half-half mixture of plant lipids and dairy lipids (DL), or this mixture supplemented with Lf (DL + Lf). They were weaned on a standard diet and challenged with a high-energy diet until postnatal day 140. DL and DL + Lf modulated gut microbiota composition and metabolism, increasing abundance of several Clostridia genera. Moreover, DL + Lf specifically decreased the faecal content of 2-oxoglutarate and lysine compared to PL and 5-aminovalerate compared to PL and DL. It also increased short-chain fatty acid concentrations like propionate compared to DL. Furthermore, DL + Lf had a beneficial effect on the endocrine function, enhancing caecal GLP-1 and GLP-1 meal-stimulated secretion. Correlations highlighted the consistent relationship between microbiota and gut physiology. Together, our results evidence a beneficial programming effect of DL + Lf in infant formula composition on faecal microbiota and entero-insular axis function.
Published: 2018

47. Using ASICS to quantify metabolites in 1D 1H NMR spectra: an application to perinatal survival in pigs

Author: Gaëlle Lefort, Laurence Liaubet, Patrick Tardivel, Cécile Canlet, Marie Tremblay-Franco, Laurent Debrauwer, Nathalie Villa-Vialaneix, Rémi Servien, Unité de Mathématiques et Informatique Appliquées de Toulouse (MIAT INRA), Institut National de la Recherche Agronomique (INRA), Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-École nationale supérieure agronomique de Toulouse (ENSAT), Université de Toulouse (UT)-Université de Toulouse (UT), Institut de Mathématiques de Toulouse UMR5219 (IMT), Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), MetaToul AXIOM (E20), ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-MetaboHUB-MetaToul, MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Innovations Thérapeutiques et Résistances (InTheRes), DigitAG, École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-MetaToul-MetaboHUB
Subjects: [SDV.GEN]Life Sciences [q-bio]/Genetics, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, [SDV]Life Sciences [q-bio], [INFO]Computer Science [cs], [MATH]Mathematics [math], ComputingMilieux_MISCELLANEOUS
Abstract: National audience
Published: 2018

48. Quantification of lipids: Model, reality, and compromise

Author: Cécile Canlet, Juliette Jouhet, Olivier Berdeaux, Spiro Khoury, Marlène Z. Lacroix, Justine Bertrand-Michel, Bertrand-Michel, Justine, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Physiologie cellulaire et végétale (LPCV), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), by the French National Infrastructure MetaboHUB ANR-11-INBS-010, by the Région Occitanie, the Centre National de la Recherche Scientifique (CNRS), the Institut National de la Recherche Agronomique (INRA) and the Institut National de la Santé et de la Recherche Medicale (Inserm)., Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Metatoul AXIOM (E20 ), MetaboHUB-MetaToul, MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-ToxAlim (ToxAlim), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Toulouse (UT)-Université de Toulouse (UT), Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Institut des Maladies Métaboliques et Casdiovasculaires (UPS/Inserm U1297 - I2MC), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANR-11-INBS-0010,METABOHUB,Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation(2011), Martin-Laffon, Jacqueline, Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation - - METABOHUB2011 - ANR-11-INBS-0010 - INBS - VALID, Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-ToxAlim (ToxAlim), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-MetaToul-MetaboHUB, and Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: 0301 basic medicine, Magnetic Resonance Spectroscopy, Standardization, Computer science, Absolute quantification, lcsh:QR1-502, Review, Mass spectrometry, 01 natural sciences, Biochemistry, lcsh:Microbiology, 03 medical and health sciences, spectrométrie de masse, Lipidomics, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, lipodomic, mass spectrometry, nuclear magnetic resonance, quantification, universal detector, Molecular Biology, Crucial point, lipide, Chromatography, Quantum Physics, détecteur, 010401 analytical chemistry, résonance magnétique nucléaire, Biologie du développement, Lipid Metabolism, Lipids, Development Biology, 0104 chemical sciences, 030104 developmental biology, lipidomic, Biochemical engineering, Physique Quantique
Abstract: Revue non répertoriée dans le JCR.; International audience; Lipids are key molecules in various biological processes, thus their quantification is a crucial point in a lot of studies and should be taken into account in lipidomics development. This family is complex and presents a very large diversity of structures, so analyzing and quantifying all this diversity is a real challenge. In this review, the different techniques to analyze lipids will be presented: from nuclear magnetic resonance (NMR) to mass spectrometry (with and without chromatography) including universal detectors. First of all, the state of the art of quantification, with the definitions of terms and protocol standardization, will be presented with quantitative lipidomics in mind, and then technical considerations and limitations of analytical chemistry's tools, such as NMR, mass spectrometry and universal detectors, will be discussed, particularly in terms of absolute quantification.
Published: 2018

49. Metabolic effects of a chronic dietary exposure to a low-dose oesticide cocktail in mice: Sexual dimorphism and role of the constitutive androstane receptor

Author: Jean-François Martin, Arnaud Polizzi, Hervé Guillou, Céline Lukowicz, Emilien L. Jamin, Cécile Canlet, Nicolas Loiseau, Laurent Debrauwer, Justine Bertrand-Michel, Vassilia Theodorou, Laurence Gamet-Payrastre, Talal Al Saati, Claire Naylies, Laila Mselli-Lakhal, Sandrine Ellero-Simatos, Alexandra Montagner, Marion Régnier, Yannick Lippi, Frédéric Lasserre, ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Toxicologie Intégrative & Métabolisme (ToxAlim-TIM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Transcriptomic impact of Xenobiotics (E23 TRiX), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Plateforme Génome & Transcriptome (GET), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-MetaToul-MetaboHUB, MetaboHUB, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM), Neuro-Gastroentérologie & Nutrition (ToxAlim-NGN), Exposition, Perturbation Endocrino-métabolique et Reproduction (ToxAlim-EXPER), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-MetaboHUB-MetaToul, ProdInra, Migration, Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Plateforme Génome & Transcriptome (GET), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-MetaToul-MetaboHUB
Subjects: 0301 basic medicine, Male, Insecticides, Health, Toxicology and Mutagenesis, [SDV]Life Sciences [q-bio], Physiology, Receptors, Cytoplasmic and Nuclear, 010501 environmental sciences, 01 natural sciences, Animals, Genetically Modified, Dietary Exposure, 03 medical and health sciences, chemistry.chemical_compound, Mice, Sex Factors, Glucose Metabolism Disorder, Constitutive androstane receptor, medicine, Metabolome, Animals, Receptor, Toxicity Tests, Chronic, Constitutive Androstane Receptor, 0105 earth and related environmental sciences, Glucose Metabolism Disorders, business.industry, Research, Fatty liver, Body Weight, Public Health, Environmental and Occupational Health, Glutathione, Pesticide, medicine.disease, Fungicides, Industrial, Sexual dimorphism, Fatty Liver, Mice, Inbred C57BL, [SDV] Life Sciences [q-bio], 030104 developmental biology, chemistry, Liver, Inactivation, Metabolic, Female, business
Abstract: Background: Epidemiological evidence suggests a link between pesticide exposure and the development of metabolic diseases. However, most experimental studies have evaluated the metabolic effects of pesticides using individual molecules, often at nonrelevant doses or in combination with other risk factors such as high-fat diets. Objectives: We aimed to evaluate, in mice, the metabolic consequences of chronic dietary exposure to a pesticide mixture at nontoxic doses, relevant to consumers’ risk assessment. Methods: A mixture of six pesticides commonly used in France, i.e., boscalid, captan, chlorpyrifos, thiofanate, thiacloprid, and ziram, was incorporated in a standard chow at doses exposing mice to the tolerable daily intake (TDI) of each pesticide. Wild-type (WT) and constitutive androstane receptor–deficient (CAR−/−) male and female mice were exposed for 52 wk. We assessed metabolic parameters [body weight (BW), food and water consumption, glucose tolerance, urinary metabolome] throughout the experiment. At the end of the experiment, we evaluated liver metabolism (histology, transcriptomics, metabolomics, lipidomics) and pesticide detoxification using liquid chromatography–mass spectrometry (LC-MS). Results: Compared to those fed control chow, WT male mice fed pesticide chow had greater BW gain and more adiposity. Moreover, these WT males fed pesticide chow exhibited characteristics of hepatic steatosis and glucose intolerance, which were not observed in those fed control chow. WT exposed female mice exhibited fasting hyperglycemia, higher reduced glutathione (GSH):oxidized glutathione (GSSG) liver ratio and perturbations of gut microbiota–related urinary metabolites compared to WT mice fed control chow. When we performed these experiments on CAR−/− mice, pesticide-exposed CAR−/− males did not exhibit BW gain or changes in glucose metabolism compared to the CAR−/− males fed control chow. Moreover, CAR−/− females fed pesticide chow exhibited pesticide toxicity with higher BWs and mortality rate compared to the CAR−/− females fed control chow. Conclusions: To our knowledge, we are the first to demonstrate a sexually dimorphic obesogenic and diabetogenic effect of chronic dietary exposure to a common mixture of pesticides at TDI levels, and to provide evidence for a partial role for CAR in an in vivo mouse model. This raises questions about the relevance of TDI for individual pesticides when present in a mixture. https://doi.org/10.1289/EHP2877
Published: 2018

50. Genotoxicity of aflatoxins and their precursors in human cells

Author: Cécile Canlet, Marc Audebert, Olivier Puel, Isabelle P. Oswald, Selma P. Snini, Souria Tadrist, Martin G. Theumer, Laure Khoury, Yasmine Henneb, ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), Métabolisme et Xénobiotiques (ToxAlim-MeX), ProdInra, Migration, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-MetaboHUB-MetaToul, Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), and Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Aflatoxin, Aflatoxin B1, Sterigmatocystin, [SDV]Life Sciences [q-bio], GENOTOXICITY, Anthraquinones, Toxicology, medicine.disease_cause, Activation, Metabolic, Histones, chemistry.chemical_compound, Aflatoxins, heterocyclic compounds, H2AX, Cytotoxicity, Chemistry, food and beverages, Hep G2 Cells, 04 agricultural and veterinary sciences, General Medicine, Bioquímica y Biología Molecular, 040401 food science, 3. Good health, [SDV] Life Sciences [q-bio], Biochemistry, Biological Assay, Micología, CIENCIAS NATURALES Y EXACTAS, Cell Survival, DNA damage, METABOLISM, Risk Assessment, DNA DAMAGE, Ciencias Biológicas, 03 medical and health sciences, 0404 agricultural biotechnology, medicine, Humans, Carcinogen, Dose-Response Relationship, Drug, Mutagenicity Tests, genotoxicity, technology, industry, and agriculture, aflatoxin, Metabolism, biological factors, AFLATOXIN, 030104 developmental biology, Cell culture, metabolism, Biomarkers, Genotoxicity
Abstract: Aflatoxins are found as food contaminant and some of them demonstrate a carcinogenic effect. The aflatoxins biosynthetic pathway involves 15 successive steps. The aim of this study was to compare the toxicity of aflatoxins and their precursors in three human cell lines. We tested the four aflatoxins and two of their metabolites; three early metabolic precursors and two late biosynthetic precursors. Cyclopiazonic acid, synthesized in parallel with aflatoxins, was also tested. The cytotoxicity and the genotoxicity was evaluated with the γH2AX assay in three human cell lines with different bioactivation capacities. Our results indicated that the most genotoxic chemicals in the three cell lines were in decreasing order sterigmatocystin (ST), aflatoxin B1 (AFB1), aflatoxicol (AFL), aflatoxin G1 (AFG1) and versicolorin A (VERA). Aflatoxin M1 (AFM1) demonstrated genotoxic property in only one cell line. The other tested compounds did not demonstrate any genotoxic activity. Overall, our results suggested different genotoxic mechanisms of action for the tested compounds, involving specific bioactivation pathways. Moreover, some metabolic precursors of aflatoxins demonstrated genotoxic potential equivalent or greater to AFB1. This should be taking into account for the development of new strategies intended to reduce the aflatoxins exposure and for human risk assessment. Fil: Theumer, Martín Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Université de Toulouse; Francia. Institut National de la Recherche Agronomique; Francia Fil: Henneb, Y.. Institut National de la Recherche Agronomique; Francia. Université de Toulouse; Francia Fil: Khoury, L.. Institut National de la Recherche Agronomique; Francia. Université de Toulouse; Francia Fil: Snini, S.P.. Université de Toulouse; Francia. Institut National de la Recherche Agronomique; Francia Fil: Tadrist, S.. Institut National de la Recherche Agronomique; Francia. Université de Toulouse; Francia Fil: Canlet, C.. Institut National de la Recherche Agronomique; Francia. Université de Toulouse; Francia Fil: Puel, O.. Université de Toulouse; Francia. Institut National de la Recherche Agronomique; Francia Fil: Oswald, I.P.. Institut National de la Recherche Agronomique; Francia. Université de Toulouse; Francia Fil: Audebert, M.. Institut National de la Recherche Agronomique; Francia. Université de Toulouse; Francia
Published: 2018

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