Obesity-associated deficits in inhibitory control are phenocopied to mice through gut microbiota changes in one-carbon and aromatic amino acids metabolic pathways

Background Inhibitory control (IC) is critical to keep long-term goals in everyday life. Bidirectional relationships between IC deficits and obesity are behind unhealthy eating and physical exercise habits. Methods We studied gut microbiome composition and functionality, and plasma and faecal metabo...

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Autores: Arnoriaga Rodríguez, María, Mayneris Perxachs, Jordi, Contreras-Rodríguez, Oren, Burokas, Aurelijus, Ortega Sánchez, Juan Antonio, Blasco Solà, Gerard, Coll, Claudia, Biarnés, Carles, Castells Nobau, Anna, Puig, Josep, Garre Olmo, Josep, Ramos, Rafel, Pedraza, Salvador, Brugada, Ramon, Vilanova, Joan Carles, Serena, Joaquín, Barretina Ginesta, Jordi, Gich Fullà, Jordi, Pérez Brocal, Vicente, Moya, Andrés, Fernández Real, Xavier, Ramió Torrentà, Lluís, Pamplona Gras, Reinald, Sol, Joaquim, Jové Font, Mariona, Ricart, Wifredo, Portero Otín, Manuel, Maldonado, Rafael, Fernández Real, José Manuel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Universitat de Lleida (UdL)
Repositorio:Repositori Obert UdL
OAI Identifier:oai:repositori.udl.cat:10459.1/71488
Acceso en línea:https://doi.org/10.1136/gutjnl-2020-323371
http://hdl.handle.net/10459.1/71488
Access Level:acceso abierto
Palabra clave:Intestinal microbiology
Obesity
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network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Obesity-associated deficits in inhibitory control are phenocopied to mice through gut microbiota changes in one-carbon and aromatic amino acids metabolic pathways
title Obesity-associated deficits in inhibitory control are phenocopied to mice through gut microbiota changes in one-carbon and aromatic amino acids metabolic pathways
spellingShingle Obesity-associated deficits in inhibitory control are phenocopied to mice through gut microbiota changes in one-carbon and aromatic amino acids metabolic pathways
Arnoriaga Rodríguez, María
Intestinal microbiology
Obesity
title_short Obesity-associated deficits in inhibitory control are phenocopied to mice through gut microbiota changes in one-carbon and aromatic amino acids metabolic pathways
title_full Obesity-associated deficits in inhibitory control are phenocopied to mice through gut microbiota changes in one-carbon and aromatic amino acids metabolic pathways
title_fullStr Obesity-associated deficits in inhibitory control are phenocopied to mice through gut microbiota changes in one-carbon and aromatic amino acids metabolic pathways
title_full_unstemmed Obesity-associated deficits in inhibitory control are phenocopied to mice through gut microbiota changes in one-carbon and aromatic amino acids metabolic pathways
title_sort Obesity-associated deficits in inhibitory control are phenocopied to mice through gut microbiota changes in one-carbon and aromatic amino acids metabolic pathways
dc.creator.none.fl_str_mv Arnoriaga Rodríguez, María
Mayneris Perxachs, Jordi
Contreras-Rodríguez, Oren
Burokas, Aurelijus
Ortega Sánchez, Juan Antonio
Blasco Solà, Gerard
Coll, Claudia
Biarnés, Carles
Castells Nobau, Anna
Puig, Josep
Garre Olmo, Josep
Ramos, Rafel
Pedraza, Salvador
Brugada, Ramon
Vilanova, Joan Carles
Serena, Joaquín
Barretina Ginesta, Jordi
Gich Fullà, Jordi
Pérez Brocal, Vicente
Moya, Andrés
Fernández Real, Xavier
Ramió Torrentà, Lluís
Pamplona Gras, Reinald
Sol, Joaquim
Jové Font, Mariona
Ricart, Wifredo
Portero Otín, Manuel
Maldonado, Rafael
Fernández Real, José Manuel
author Arnoriaga Rodríguez, María
author_facet Arnoriaga Rodríguez, María
Mayneris Perxachs, Jordi
Contreras-Rodríguez, Oren
Burokas, Aurelijus
Ortega Sánchez, Juan Antonio
Blasco Solà, Gerard
Coll, Claudia
Biarnés, Carles
Castells Nobau, Anna
Puig, Josep
Garre Olmo, Josep
Ramos, Rafel
Pedraza, Salvador
Brugada, Ramon
Vilanova, Joan Carles
Serena, Joaquín
Barretina Ginesta, Jordi
Gich Fullà, Jordi
Pérez Brocal, Vicente
Moya, Andrés
Fernández Real, Xavier
Ramió Torrentà, Lluís
Pamplona Gras, Reinald
Sol, Joaquim
Jové Font, Mariona
Ricart, Wifredo
Portero Otín, Manuel
Maldonado, Rafael
Fernández Real, José Manuel
author_role author
author2 Mayneris Perxachs, Jordi
Contreras-Rodríguez, Oren
Burokas, Aurelijus
Ortega Sánchez, Juan Antonio
Blasco Solà, Gerard
Coll, Claudia
Biarnés, Carles
Castells Nobau, Anna
Puig, Josep
Garre Olmo, Josep
Ramos, Rafel
Pedraza, Salvador
Brugada, Ramon
Vilanova, Joan Carles
Serena, Joaquín
Barretina Ginesta, Jordi
Gich Fullà, Jordi
Pérez Brocal, Vicente
Moya, Andrés
Fernández Real, Xavier
Ramió Torrentà, Lluís
Pamplona Gras, Reinald
Sol, Joaquim
Jové Font, Mariona
Ricart, Wifredo
Portero Otín, Manuel
Maldonado, Rafael
Fernández Real, José Manuel
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Intestinal microbiology
Obesity
topic Intestinal microbiology
Obesity
description Background Inhibitory control (IC) is critical to keep long-term goals in everyday life. Bidirectional relationships between IC deficits and obesity are behind unhealthy eating and physical exercise habits. Methods We studied gut microbiome composition and functionality, and plasma and faecal metabolomics in association with cognitive tests evaluating inhibitory control (Stroop test) and brain structure in a discovery (n=156), both cross-sectionally and longitudinally, and in an independent replication cohort (n=970). Faecal microbiota transplantation (FMT) in mice evaluated the impact on reversal learning and medial prefrontal cortex (mPFC) transcriptomics. Results An interplay among IC, brain structure (in humans) and mPFC transcriptomics (in mice), plasma/faecal metabolomics and the gut metagenome was found. Obesity-dependent alterations in one-carbon metabolism, tryptophan and histidine pathways were associated with IC in the two independent cohorts. Bacterial functions linked to one-carbon metabolism (thyX,dut, exodeoxyribonuclease V), and the anterior cingulate cortex volume were associated with IC, cross-sectionally and longitudinally. FMT from individuals with obesity led to alterations in mice reversal learning. In an independent FMT experiment, human donor’s bacterial functions related to IC deficits were associated with mPFC expression of one-carbon metabolism-related genes of recipient’s mice. Conclusion These results highlight the importance of targeting obesity-related impulsive behaviour through the induction of gut microbiota shifts.
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://doi.org/10.1136/gutjnl-2020-323371
http://hdl.handle.net/10459.1/71488
url https://doi.org/10.1136/gutjnl-2020-323371
http://hdl.handle.net/10459.1/71488
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/MINECO//SAF2015-65878-R
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2017-84060-R
Reproducció del document publicat a: http://doi.org/10.1136/gutjnl-2020-323371
Gut, 2021, vol. 0, p. 1-14
info:eu-repo/grantAgreement/EC/FP7/602891
dc.rights.none.fl_str_mv cc-by-nc, (c) Armoriaga et al., 2021
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc/4.0/
rights_invalid_str_mv cc-by-nc, (c) Armoriaga et al., 2021
http://creativecommons.org/licenses/by-nc/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv BMJ Publishing Group
British Society of Gastroenterology
publisher.none.fl_str_mv BMJ Publishing Group
British Society of Gastroenterology
dc.source.none.fl_str_mv reponame:Repositori Obert UdL
instname:Universitat de Lleida (UdL)
instname_str Universitat de Lleida (UdL)
reponame_str Repositori Obert UdL
collection Repositori Obert UdL
repository.name.fl_str_mv
repository.mail.fl_str_mv
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spelling Obesity-associated deficits in inhibitory control are phenocopied to mice through gut microbiota changes in one-carbon and aromatic amino acids metabolic pathwaysArnoriaga Rodríguez, MaríaMayneris Perxachs, JordiContreras-Rodríguez, OrenBurokas, AurelijusOrtega Sánchez, Juan AntonioBlasco Solà, GerardColl, ClaudiaBiarnés, CarlesCastells Nobau, AnnaPuig, JosepGarre Olmo, JosepRamos, RafelPedraza, SalvadorBrugada, RamonVilanova, Joan CarlesSerena, JoaquínBarretina Ginesta, JordiGich Fullà, JordiPérez Brocal, VicenteMoya, AndrésFernández Real, XavierRamió Torrentà, LluísPamplona Gras, ReinaldSol, JoaquimJové Font, MarionaRicart, WifredoPortero Otín, ManuelMaldonado, RafaelFernández Real, José ManuelIntestinal microbiologyObesityBackground Inhibitory control (IC) is critical to keep long-term goals in everyday life. Bidirectional relationships between IC deficits and obesity are behind unhealthy eating and physical exercise habits. Methods We studied gut microbiome composition and functionality, and plasma and faecal metabolomics in association with cognitive tests evaluating inhibitory control (Stroop test) and brain structure in a discovery (n=156), both cross-sectionally and longitudinally, and in an independent replication cohort (n=970). Faecal microbiota transplantation (FMT) in mice evaluated the impact on reversal learning and medial prefrontal cortex (mPFC) transcriptomics. Results An interplay among IC, brain structure (in humans) and mPFC transcriptomics (in mice), plasma/faecal metabolomics and the gut metagenome was found. Obesity-dependent alterations in one-carbon metabolism, tryptophan and histidine pathways were associated with IC in the two independent cohorts. Bacterial functions linked to one-carbon metabolism (thyX,dut, exodeoxyribonuclease V), and the anterior cingulate cortex volume were associated with IC, cross-sectionally and longitudinally. FMT from individuals with obesity led to alterations in mice reversal learning. In an independent FMT experiment, human donor’s bacterial functions related to IC deficits were associated with mPFC expression of one-carbon metabolism-related genes of recipient’s mice. Conclusion These results highlight the importance of targeting obesity-related impulsive behaviour through the induction of gut microbiota shifts.This work was partially supported by research grants FIS (PI15/01934 and PI18/01022) from the Instituto de Salud Carlos III from Spain, SAF2015- 65878-R and #AEI-SAF2017-84060-R-FEDER from Ministry of Economy and Competitiveness, Prometeo/2018/A/133 from Generalitat Valenciana, Spain; and also by Fondo Europeo de Desarrollo Regional (FEDER) funds, European Commission (FP7, NeuroPain #2013-602891), the Catalan Government (AGAUR, #SGR2017-669, ICREA Academia Award 2015), the Spanish Instituto de Salud Carlos III (RTA, #RD16/0017/0020), the Spanish Ministry of Science, Innovation and Universities (RTI2018-099200-B-I00), the Catalan Goverment (Agency for Management of University and Research Grants [2017SGR696] and Department of Health [STL002/16/00250]; the European Regional Development Fund (project No. 01.2.2-LMT-K-718-02-0014) under grant agreement with the Research Council of Lithuania (LMTLT); and the Project ThinkGut (EFA345/19) 65% co-financed by the European Regional Development Fund (ERDF) through the Interreg V-A SpainFrance-Andorra programme (POCTEFA 2014-2020). MA-R is funded by a predoctoral Río Hortega contract from the Instituto de Salud Carlos III (ISCIII, CM19/00190), co-funded by the European Social Fund “Investing in your future”. OC-R is funded by the Miguel Servet Program from the Instituto de Salud Carlos III (ISCIII CP20/00165), co-funded by the Europeran Social Fund "Investing in your future". JM-P is funded by the Miguel Servet Program from the Instituto de Salud Carlos III (ISCIII CP18/00009), co-funded by the European Social Fund “Investing in your future”. JS is funded by a predoctoral PERIS contract (SLT002/16/00250) from the Catalan Government. MJ is a professor under the “Serra Hunter” programme (Generalitat de Catalunya).BMJ Publishing GroupBritish Society of Gastroenterology2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://doi.org/10.1136/gutjnl-2020-323371http://hdl.handle.net/10459.1/71488reponame:Repositori Obert UdL instname:Universitat de Lleida (UdL)Inglésinfo:eu-repo/grantAgreement/MINECO//SAF2015-65878-Rinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2017-84060-RReproducció del document publicat a: http://doi.org/10.1136/gutjnl-2020-323371Gut, 2021, vol. 0, p. 1-14info:eu-repo/grantAgreement/EC/FP7/602891cc-by-nc, (c) Armoriaga et al., 2021info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc/4.0/oai:repositori.udl.cat:10459.1/714882026-06-24T12:42:17Z
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