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

dc.contributor.authorArnoriaga Rodríguez, María
dc.contributor.authorMayneris Perxachs, Jordi
dc.contributor.authorContreras-Rodríguez, Oren
dc.contributor.authorBurokas, Aurelijus
dc.contributor.authorOrtega Sánchez, Juan Antonio
dc.contributor.authorBlasco Solà, Gerard
dc.contributor.authorColl, Claudia
dc.contributor.authorBiarnés, Carles
dc.contributor.authorCastells Nobau, Anna
dc.contributor.authorPuig, Josep
dc.contributor.authorGarre Olmo, Josep
dc.contributor.authorRamos, Rafel
dc.contributor.authorPedraza, Salvador
dc.contributor.authorBrugada, Ramon
dc.contributor.authorVilanova, Joan Carles
dc.contributor.authorSerena, Joaquín
dc.contributor.authorBarretina Ginesta, Jordi
dc.contributor.authorGich Fullà, Jordi
dc.contributor.authorPérez Brocal, Vicente
dc.contributor.authorMoya, Andrés
dc.contributor.authorFernández Real, Xavier
dc.contributor.authorRamió Torrentà, Lluís
dc.contributor.authorPamplona Gras, Reinald
dc.contributor.authorSol, Joaquim
dc.contributor.authorJové Font, Mariona
dc.contributor.authorRicart, Wifredo
dc.contributor.authorPortero Otín, Manuel
dc.contributor.authorMaldonado, Rafael
dc.contributor.authorFernández Real, José Manuel
dc.date.accessioned2021-06-22T11:00:54Z
dc.date.available2021-06-22T11:00:54Z
dc.date.issued2021-01
dc.description.abstractBackground 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.ca_ES
dc.description.sponsorshipThis 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).ca_ES
dc.identifier.doihttp://doi.org/10.1136/gutjnl-2020-323371
dc.identifier.idgrec031018
dc.identifier.issn1468-3288
dc.identifier.issn0017-5749
dc.identifier.urihttp://hdl.handle.net/10459.1/71488
dc.language.isoengca_ES
dc.publisherBMJ Publishing Groupca_ES
dc.publisherBritish Society of Gastroenterologyca_ES
dc.relationinfo:eu-repo/grantAgreement/MINECO//SAF2015-65878-R/ES/ESTABILIDAD, RESILIENCIA Y REDUNDANCIA FUNCIONAL DE LA MICROBIOTA INTESTINAL HUMANA DURANTE EL DESARROLLO Y EN RESPUESTA AL ESTRES ANTIBIOTICO Y A CLOSTRIDIUM DIFFICILE/ca_ES
dc.relationinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2017-84060-R/ES/ESTRATEGIA QUIMIOGENETICA PARA LA ELUCIDACION DEL SUBSTRATO NEUROBIOLOGICO DE LA PERDIDA DE CONTROL DE LA INGESTA ALIMENTARIA/ca_ES
dc.relation.isformatofReproducció del document publicat a: http://doi.org/10.1136/gutjnl-2020-323371ca_ES
dc.relation.ispartofGut, 2021, vol. 0, p. 1-14ca_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/602891ca_ES
dc.rightscc-by-nc, (c) Armoriaga et al., 2021ca_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccessca_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/*
dc.subjectIntestinal microbiologyca_ES
dc.subjectObesityca_ES
dc.titleObesity-associated deficits in inhibitory control are phenocopied to mice through gut microbiota changes in one-carbon and aromatic amino acids metabolic pathwaysca_ES
dc.typeinfo:eu-repo/semantics/articleca_ES
dc.type.versioninfo:eu-repo/semantics/publishedVersionca_ES
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