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

Author

Huillet Marine, Lasserre Frédéric, Gratacap Marie-Pierre, Engelmann Beatrice, Bruse Justine, Polizzi Arnaud, Fougeray Tiffany, Martin Céline, Rives Clémence, Fougerat Anne, Naylies Claire, Lippi Yannick, Garcia Géraldine, Rousseau- Bacquie Elodie, Canlet Cécile, Debrauwer Laurent, Rolle-Kampczyk Ulrike, von Bergen Martin, Payrastre Bernard, Boutet-Robinet Elisa, Gamet-Payrastre Laurence, Guillou Hervé, Loiseau Nicolas, and Ellero-Simatos Sandrine

Abstract

Background and AimsThe constitutive androstane receptor (CAR) is a nuclear receptor able to recognize a large panel of xenobiotics leading to the modulation of the expression of its target genes involved in xenobiotic detoxication and energy metabolism. While CAR hepatic activity is thought to be higher in women than in men, its response to an acute pharmacological activation has never been investigated in both sexes.MethodsHepatic transcriptome, plasma and hepatic metabolome, have been analyzed inCar+/+andCar-/-male and female mice treated either with the CAR-specific agonist, 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), or with vehicle.ResultsWhile 90% of TCPOBOP-sensitive genes were modulated in a sex- independent way, the remaining 10% were almost exclusively impacted in female liver specifically. These female-specific CAR-sensitive genes were mainly involved in xenobiotic metabolism, inflammation and extracellular matrix organization. CAR activation also induced higher hepatic oxidative stress and hepatocyte cytolysis in females than in males. Data mining on human data confirmed that CAR activation may be involved in sexually-dimorphic drug-induced liver injury. Hepatic expression of flavin monooxygenase 3(Fmo3)was almost abolished and associated with a decrease of hepatic trimethylamine-N-oxide (TMAO) concentration in TCPOBOP-treated females. In line with a possible role in the control of TMAO homeostasis, CAR activation decreased platelet hyperresponsiveness in female mice supplemented with dietary choline.ConclusionsOur results demonstrate that more than 10% of CAR-sensitive genes are sex-specific and influence hepatic and systemic response such as platelet aggregation. Also, CAR activation may be an important mechanism of sexually- dimorphic drug-induced liver injury.

Published
2023

2. D15.6 - Results of the joint survey on HBM mixtures

Author

Ottenbros, Ilse, Lebret, Erik, Huber, Carolin, Lommen, Arjen, Antignac, Jean-Philippe, Čupr, Pavel, Šulc, Libor, Szigeti, Tamás, Középesy, Szilvia, Martinsone, Inese, Martinsone, Zanna, Pardo, Olga, Fernández, Sandra, Coscollá, Clara, Pedraza Diaz, Susana, Ammann, Priska, Jacobs, Anne, Probst-Hensch, Nicole, Imboden, Medea, Keidel, Dirk, Krauss, Martin, Debrauwer, Laurent, Wagner, Kevin, Nijssen, Rosalie, Mol, Hans, Vitale, Chiara Maria, Klanova, Jana, Garlito, Borja, León, Nuria, Luijten, Mirjam, and Vlaanderen, Jelle

Abstract

This deliverable describes the results of the joint pesticide survey ’SPECIMEn’ in five partner countries: Czech Republic, Hungary, Latvia, Spain and the Netherlands. It also contains a report on the implementation of a study conducted in Switzerland, which has a different design, but data was harmonised as much as possible. In all participating partner countries, urine samples have been collected in two seasons, i.e., winter 2019/2020 and summer 2020. Per country at least 100 locations have been included, of which about half are located in so-called hotspot areas. On the collected urine samples, a harmonised suspect screening method was applied to detect multiple pesticide-related markers. The deliverable describes the results obtained with this analysis.

Published
2022
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3. Assessment of exposure to pesticide mixtures in five European countries by a harmonized urinary suspect screening approach

Author

Ottenbros, Ilse, Lebret, Erik, Huber, Carolin, Lommen, Arjen, Antignac, Jean-Philippe, Čupr, Pavel, Šulc, Libor, Mikeš, Ondřej, Szigeti, Tamás, Középesy, Szilvia, Martinsone, Inese, Martinsone, Zanna, Akulova, Lasma, Pardo, Olga, Fernández, Sandra F, Coscollá, Clara, Pedraza-Diaz, Susana, Krauss, Martin, Debrauwer, Laurent, Wagner, Kévin, Nijssen, Rosalie, Mol, Hans, Vitale, Chiara Maria, Klanova, Jana, Molina, Borja Garlito, León, Nuria, Vermeulen, Roel, Luijten, Mirjam, Vlaanderen, Jelle, IRAS OH Epidemiology Chemical Agents, IRAS OH Epidemiology Microbial Agents, Unión Europea. Comisión Europea. H2020, Ministry of Education, Youth and Sports (República Checa), IRAS OH Epidemiology Chemical Agents, IRAS OH Epidemiology Microbial Agents, National Institute for Public Health and the Environment [Bilthoven] (RIVM), Institute for Risk Assessment Sciences [Utrecht, The Netherlands] (IRAS), Utrecht University [Utrecht], Helmholtz Zentrum für Umweltforschung = Helmholtz Centre for Environmental Research (UFZ), Goethe-University Frankfurt am Main, Wageningen University and Research [Wageningen] (WUR), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Laboratoire d'étude des Résidus et Contaminants dans les Aliments (LABERCA), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Research Centre for Toxic Compounds in the Environment [Brno] (RECETOX / MUNI), Faculty of Science [Brno] (SCI / MUNI), Masaryk University [Brno] (MUNI)-Masaryk University [Brno] (MUNI), National center for public health [Hungary], Riga Stradins University (RSU), Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana [Espagne] (FISABIO), Institute of Health Carlos III, 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), Universitat Jaume I, Tuberculosis Reference Laboratory [RIVM], This project has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 733032 HBM4EU, No 857560and No 857340. P.Č. O.M. & L.Š. acknowledge the RECETOX research infrastructure supported by the Ministry of Education, Youth and Sports of the Czech Republic (LM2018121) and the Ministry of Education, Youth and Sports of the Czech Republic (CZ.02.1.01/0.0/0.0/17_043/0009632)., and European Project: 733032,H2020,HBM4EU(2017)

Subjects
Adult, HBM4EU, [SDV]Life Sciences [q-bio], Public Health, Environmental and Occupational Health, Agriculture, Chlorpropham, Environmental Exposure, Suspect screening, Correlation patterns, Team Pesticides 2, Pesticide exposure, Europe, Mixtures, Co-occurrence, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Pesticides, Biomarkers, VLAG
Abstract

Humans are exposed to a mixture of pesticides through diet as well as through the environment. We conducted a suspect-screening based study to describe the probability of (concomitant) exposure to a set of pesticide profiles in five European countries (Latvia, Hungary, Czech Republic, Spain and the Netherlands). We explored whether living in an agricultural area (compared to living in a peri-urban area), being a a child (compared to being an adult), and the season in which the urine sample was collected had an impact on the probability of detection of pesticides (-metabolites). In total 2088 urine samples were collected from 1050 participants (525 parent-child pairs) and analyzed through harmonized suspect screening by five different laboratories. Fourty pesticide biomarkers (either pesticide metabolites or the parent pesticides as such) relating to 29 pesticides were identified at high levels of confidence in samples across all study sites. Most frequently detected were biomarkers related to the parent pesticides acetamiprid and chlorpropham. Other biomarkers with high detection rates in at least four countries related to the parent pesticides boscalid, fludioxonil, pirimiphos-methyl, pyrimethanil, clothianidin, fluazifop and propamocarb. In 84% of the samples at least two different pesticides were detected. The median number of detected pesticides in the urine samples was 3, and the maximum was 13 pesticides detected in a single sample. The most frequently co-occurring substances were acetamiprid with chlorpropham (in 62 urine samples), and acetamiprid with tebuconazole (30 samples). Some variation in the probability of detection of pesticides (-metabolites) was observed with living in an agricultural area or season of urine sampling, though no consistent patterns were observed. We did observe differences in the probability of detection of a pesticide (metabolite) among children compared to adults, suggesting a different exposure and/or elimination patterns between adults and children. This survey demonstrates the feasibility of conducting a harmonized pan-European sample collection, combined with suspect screening to provide insight in the presence of exposure to pesticide mixtures in the European population, including agricultural areas. Future improvements could come from improved (harmonized) quantification of pesticide levels. This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 733032 HBM4EU, No 857560 and No 857340. P.C., O.M. & L.S. acknowledge the RECETOX research infrastructure supported by the Ministry of Education, Youth and Sports of the Czech Republic (LM2018121) and the Ministry of Education, Youth and Sports of the Czech Republic (CZ.02.1.01/0.0/0.0/17_043/0009632). This publication reflects only the author’s view and the European Commission is not responsible for any use that may be made of the information it contains. BG was supported by the Margarita Salas postdoctoral contract MGS/2021/25 (UP2021-021) financed by the European UnionNextGenerationEU. Sí

Published
2023

4. Results of the joint survey on HBM mixtures Deliverable Report D15.6 WP15 Mixtures, HBM and human health risks

Author

Mirjiam Luijten, Lebret, Erik, Huber, Carolin, Jean-Philippe Antignac, Cupr, Pavel, Sulc, Libor, Szigeti, Tamas, Kozepesy, Szilvia, Martinsone, Inese, Martinsone, Zanna, Pardo, Olga, Fernández, Sandra F., Coscollà, Clara, Pedraza, Susana, Ammann, Priska, Jacobs, Anne, Probst-Hensch, Nicole, Imboden, Medea, Keidel, Dirk, Krauss, Martin, Debrauwer, Laurent, Wagner, Kevin, Nijssen, Rosalie, H. G.J. Mol, Vitale, Chiara Maria, Klanova, Jana, Molina, Borja Garlito, and León, Nuria

Published
2022
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5. Additional file 1 of Prospective association between dietary pesticide exposure profiles and type 2 diabetes risk in the NutriNet-Santé cohort

Author

Rebouillat, Pauline, Vidal, Rodolphe, Cravedi, Jean-Pierre, Taupier-Letage, Bruno, Debrauwer, Laurent, Gamet-Payrastre, Laurence, Guillou, Hervé, Touvier, Mathilde, Fezeu, Léopold K., Hercberg, Serge, Lairon, Denis, Baudry, Julia, and Kesse-Guyot, Emmanuelle

Abstract

Additional file 1: Supplementary Material1. Description of the Chemischesund Veterinäruntersuchungsamtpesticide exposure database. Supplementary Material 2. Flowchart fordecomposition of ingredients and matching. Supplementary Material 3. 180 ingredients afterdecomposition. Supplementary Material 4. Details on thecomputation of the simplified Programme National Nutrition Santé Guideline Score2 (sPNNS-GS2 score). Supplementary Material 5. Details of the Non-Negative Matrix Factorization (NMF) procedure. Supplementary Table 1. Characteristics of quintiles forNMF Component 1, NutriNet-Santé Study, 2014 (N=33,013). Supplementary Table 2. Nutritional characteristics of the participants across quintiles of NMFcomponent 1, NutriNet-Santé Study, 2014 (N=33,013). Supplementary Table 3. Characteristics of quintiles for NMF Component 2, NutriNet-Santé Study, 2014(N=33,013). Supplementary Table 4 . Nutritional characteristics of the participants across quintiles of NMFcomponent 2, NutriNet-Santé Study, 2014 (N=33,013). Supplementary Table 5. Characteristics of quintiles for NMF Component 3, NutriNet-Santé Study, 2014(N=33,013). Supplementary Table 6 . Nutritional characteristics of the participants across quintiles of NMFcomponent 3, NutriNet-Santé Study, 2014 (N=33,013). Supplementary Table 7. Characteristics of quintiles for NMF Component 4, NutriNet-Santé Study, 2014(N=33,013). Supplementary Table 8 . Nutritional characteristics of the participants across quintiles of NMFcomponent 4, NutriNet-Santé Study, 2014 (N=33,013). Supplementary Table 9. Estimated dietary pesticide exposure across NMF Components 1 and 2 quintiles(in μg/kg of weight/day), NutriNet-Santé Study, 2014 (N=33,013). Supplementary Table 10. Estimated dietary pesticide exposure across NMF Components 3 and 4 quintiles(in μg/kg of weight/day), NutriNet-Santé Study, 2014 (N=33,013). Supplementary Table 11. Expected links between metabolites and parent compounds. Supplementary Table 12. Urinaryconcentrations (µg/g creatinine) for parent compounds and metabolites in NMFComponents 1 and 2 quintiles, NutriNet-Santé Study (N=296). Supplementary Table 13. Urinaryconcentrations (µg/g creatinine) for parent compounds and metabolites in NMFComponents 3 and 4 quintiles, NutriNet-Santé Study (N=296).

Published
2022
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6. A large scale multi-laboratory suspect screening of pesticide metabolites in human biomonitoring: From tentative annotations to verified occurrences

Author

Huber, Carolin, Nijssen, Rosalie, Mol, Hans, Philippe Antignac, Jean, Krauss, Martin, Brack, Werner, Wagner, Kevin, Debrauwer, Laurent, Maria Vitale, Chiara, James Price, Elliott, Klanova, Jana, Garlito Molina, Borja, Leon, Nuria, Pardo, Olga, Fernández, Sandra F, Szigeti, Tamás, Középesy, Szilvia, Šulc, Libor, Čupr, Pavel, Mārtiņsone, Inese, Akülova, Läsma, Ottenbros, Ilse, Vermeulen, Roel, Vlaanderen, Jelle, Luijten, Mirjam, Lommen, Arjen, IRAS OH Epidemiology Chemical Agents, LESUR, Hélène, Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation - - METABOHUB2011 - ANR-11-INBS-0010 - INBS - VALID, European Human Biomonitoring Initiative - HBM4EU - - H20202017-01-01 - 2021-12-31 - 733032 - VALID, Helmholtz Zentrum für Umweltforschung = Helmholtz Centre for Environmental Research (UFZ), Goethe-University Frankfurt am Main, Wageningen University and Research [Wageningen] (WUR), Laboratoire d'étude des Résidus et Contaminants dans les Aliments (LABERCA), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-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), 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), Research Centre for Toxic Compounds in the Environment [Brno] (RECETOX / MUNI), Faculty of Science [Brno] (SCI / MUNI), Masaryk University [Brno] (MUNI)-Masaryk University [Brno] (MUNI), Universitat Jaume I, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana [Espagne] (FISABIO), Universitat de València (UV), National center for public health [Hungary], Riga Stradins University (RSU), National Institute for Public Health and the Environment [Bilthoven] (RIVM), Institute for Risk Assessment Sciences [Utrecht, The Netherlands] (IRAS), Utrecht University [Utrecht], This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 733032 HBM4EU. C.M.V., E.J.P, L.Š., P.Č. & J.K. acknowledge the RECETOX research infrastructure supported by the Ministry of Education, Youth and Sports of the Czech Republic (LM2018121) and the Ministry of Education, Youth and Sports of the Czech Republic (CZ.02.1.01/0.0/0.0/17_043/0009632). This work was supported from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 857560 and No 857340. E.J.P. acknowledges support from Czech Operational Programme Research, Development and Education - Project MSCAfellow4@MUNI (No. CZ.02.2.69/0.0/0.0/20_079/0017045). L.D. and K.W. would like to thank the MetaboHUB French National Infrastructure (MetaboHUB-ANR-11-INBS-0010, 2011). The QExactive Plus LC-HRMS used at UFZ is part of the major infrastructure initiative CITEPro (Chemicals in the Terrestrial Environment Profiler) funded by the Helmholtz Association. The Dutch Ministry of Agriculture, Nature and Food Quality are acknowledged for co-funding through projects 1277354201 and 1267333701. The European Union is acknowledged for co-funding through the European Regional Development Fund Operational Programme (ERDF) of the Valencia Region (2014-2020)., ANR-11-INBS-0010,METABOHUB,Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation(2011), European Project: 733032,H2020,HBM4EU(2017), 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 IRAS OH Epidemiology Chemical Agents

Subjects
HBM4EU, LC-HRMS, human biomonitoring, [SDV]Life Sciences [q-bio], pesticides, Suspect screening, suspect screening, exposomics, Team Pesticides 2, Pesticide metabolites, Human biomonitoring, Exposomics, Pesticides, LC-HAMS, [SDV] Life Sciences [q-bio], Environmental Science(all), pesticide urinary metabolites, General Environmental Science, VLAG
Abstract

International audience; Within the Human Biomonitoring for Europe initiative (HBM4EU), a study to determine new biomarkers of exposure to pesticides and to assess exposure patterns was conducted. Human urine samples (N = 2,088) were collected from five European regions in two different seasons. The objective of the study was to identify pesticides and their metabolites in collected urine samples with a harmonized suspect screening approach based on liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS) applied in five laboratories. A combined data processing workflow included comprehensive data reduction, correction of mass error and retention time (RT) drifts, isotopic pattern analysis, adduct and elemental composition annotation, finalized by a mining of the elemental compositions for possible annotations of pesticide metabolites. The obtained tentative annotations (n = 498) were used for acquiring representative data-dependent tandem mass spectra (MS2) and verified by spectral comparison to reference spectra generated from commercially available reference standards or produced through human liver S9 in vitro incubation experiments. 14 parent pesticides and 71 metabolites (including 16 glucuronide and 11 sulfate conjugates) were detected. Collectively these related to 46 unique pesticides.For the remaining tentative annotations either (i) no data-dependent MS2 spectra could be acquired, (ii) the spectral purity was too low for sufficient matching, or (iii) RTs indicated a wrong annotation, leaving potential for more pesticides and/or their metabolites being confirmed in further studies. Thus, the reported results are reflecting only a part of the possible pesticide exposure.

Published
2022
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7. Additional file 1 of A European proposal for quality control and quality assurance of tandem mass spectral libraries

Author

Oberacher, Herbert, Sasse, Michael, Jean-Philippe Antignac, Guitton, Yann, Debrauwer, Laurent, Jamin, Emilien L., Schulze, Tobias, Krauss, Martin, Covaci, Adrian, Caballero-Casero, Noelia, Rousseau, Kathleen, Annelaure Damont, Fenaille, François, Lamoree, Marja, and Schymanski, Emma L.

Subjects
Data_FILES
Abstract

Additional file 1. Extended description of experimental settings.

Published
2020
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8. AD15.7 - Joint survey of pesticides: details of approach and contributions

Author

Vlaanderen, Jelle, Ottenbros, Ilse, Bogers, Rik, Lebret, Erik, Vermeulen, Roel, Antignac, Jean-Philippe, Krauss, Martin, Debrauwer, Laurent, Oberacher, Herbert, Cupr, Pavel, Szigeti, Tamas, Martinsone, Inese, and Pardo, Olga

Abstract

The HBM4EU joint survey of pesticides, 'Survey on PEstiCIde Mixtures in Europe', was carried out in five partner countries: Czech Republic, Hungary, Latvia, Spain and the Netherlands. They jointly developed the details of the work protocols, translated these in local versions, selected study areas, prepared submission of documents to local Medical Ethical Review Boards and detailed the breakdown of the budget to partners institutes over the three year duration of the task 15.2 Joint Survey on Pesticides. This document summarises these activities and focusses on the details of the budgetary breakdown.

Published
2019
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9. Challenges in Clinical Metaproteomics Highlighted by the Analysis of Acute Leukemia Patients with Gut Colonization by Multidrug-Resistant Enterobacteriaceae

Author

Rechenberger, Julia, Samaras, Patroklos, Jarzab, Anna, Behr, Juergen, Frejno, Martin, Djukovic, Ana, Sanz, Jaime, González-Barberá, Eva M., Salavert, Miguel, López-Hontangas, Jose Luis, Xavier, Karina B., Debrauwer, Laurent, Rolain, Jean-Marc, Sanz, Miguel, Garcia-Garcera, Marc, Wilhelm, Mathias, Ubeda, Carles, and Kuster, Bernhard

Subjects
ddc
Published
2019

10. Challenges in Clinical Metaproteomics Highlighted by the Analysis of Acute Leukemia Patients with Gut Colonization by Multidrug-Resistant Enterobacteriaceae

Author

Rechenberger, Julia, Samaras, Patroklos, Jarzab, Anna, Behr, Juergen, Frejno, Martin, Djukovic, Ana, Sanz, Jaime, González-Barberá, Eva, Salavert, Miguel, López-Hontangas, Jose Luis, Xavier, Karina, Debrauwer, Laurent, Rolain, Jean-Marc, Sanz, Miguel, Garcia-Garcerà, Marc, Wilhelm, Mathias, Ubeda, Carles, Kuster, Bernhard, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana [Espagne] (FISABIO), Hospital Universitari i Politècnic La Fe, Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto Gulbenkian de Ciência [Oeiras] (IGC), Fundação Calouste Gulbenkian, 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), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Université de Lausanne (UNIL), CIBER in Epidemiology and Public Health, BMBF FloraStopMRE grant [031L0089], 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 National de la Recherche Agronomique (INRA)-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-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), Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, 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), and Université de Lausanne = University of Lausanne (UNIL)

Subjects
[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, human gut microbiome, data analysis, lcsh:QR1-502, multi-omics, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, lcsh:Microbiology, Article, proteomics, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, clinical proteomics, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, mass spectrometry, metaproteome, multidrug-resistant Enterobacteriaceae, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology
Abstract

International audience; The microbiome has a strong impact on human health and disease and is, therefore, increasingly studied in a clinical context. Metaproteomics is also attracting considerable attention, and such data can be efficiently generated today owing to improvements in mass spectrometry-based proteomics. As we will discuss in this study, there are still major challenges notably in data analysis that need to be overcome. Here, we analyzed 212 fecal samples from 56 hospitalized acute leukemia patients with multidrug-resistant Enterobactericeae (MRE) gut colonization using metagenomics and metaproteomics. This is one of the largest clinical metaproteomic studies to date, and the first metaproteomic study addressing the gut microbiome in MRE colonized acute leukemia patients. Based on this substantial data set, we discuss major current limitations in clinical metaproteomic data analysis to provide guidance to researchers in the field. Notably, the results show that public metagenome databases are incomplete and that sample-specific metagenomes improve results. Furthermore, biological variation is tremendous which challenges clinical study designs and argues that longitudinal measurements of individual patients are a valuable future addition to the analysis of patient cohorts.

Published
2019

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