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

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• dc.contributor.author Arnoriaga Rodríguez, María
• dc.contributor.author Burokas, Aurelijus, 1982-
• dc.contributor.author Ortega Sánchez, Juan Antonio
• dc.contributor.author Maldonado, Rafael, 1961-
• dc.contributor.author Fernández Real, Jose M.
• dc.date.accessioned 2021-03-10T06:52:38Z
• dc.date.available 2021-03-10T06:52:38Z
• dc.date.issued 2021
• dc.description.abstract 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.
• dc.description.sponsorship 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 Spain-France-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).
• dc.format.mimetype application/pdf
• dc.identifier.citation Arnoriaga-Rodríguez M, Mayneris-Perxachs J, Contreras-Rodríguez O, Burokas A, Ortega-Sanchez JA, Blasco G et al. Obesity-associated deficits in inhibitory control are phenocopied to mice through gut microbiota changes in one-carbon and aromatic amino acids metabolic pathways. Gut. 2021;70(12):2283-96. DOI: 10.1136/gutjnl-2020-323371
• dc.identifier.doi http://dx.doi.org/10.1136/gutjnl-2020-323371
• dc.identifier.issn 0017-5749
• dc.identifier.uri http://hdl.handle.net/10230/46707
• dc.language.iso eng
• dc.publisher BMJ Publishing Group
• dc.relation.ispartof Gut. 2021;70(12):2283-96
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/602891
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2015-65878-R
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/SAF2017-84060-R
• dc.rights © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. http://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
• dc.subject.keyword Intestinal microbiology
• dc.subject.keyword Obesity
• dc.title Obesity-associated deficits in inhibitory control are phenocopied to mice through gut microbiota changes in one-carbon and aromatic amino acids metabolic pathways
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion