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Title: Obesity-associated deficits in inhibitory control are phenocopied to mice through gut microbiota changes in one-carbon and aromatic amino acids metabolic pathways
Author: Arnoriaga Rodríguez, María
Mayneris Perxachs, Jordi
Contreras Rodríguez, Oren
Burokas, Aurelijus
Ortega Sanchez, Juan Antonio
Blasco, Gerard
Coll, Claudia
Biarnés, Carles
Castells Nobau, Anna
Puig, Josep
Garre Olmo, Josep
Ramos, Rafel
Pedraza, Salvador
Brugada, Ramon
Vilanova, Joan C.
Serena, Joaquín
Barretina, Jordi
Gich, Jordi
Pérez Brocal, Vicente
Moya, Andrés
Fernández Real, Xavier
Ramio Torrentà, Lluis
Pamplona, Reinald
Sol, Joaquim
Jové, Mariona
Ricart, Wifredo
Portero Otin, Manuel
Maldonado, Rafael, 1961-
Fernández Real, Jose Manuel
Keywords: Obesitat
Issue Date: 29-Jan-2021
Publisher: BMJ
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.
Note: Reproducció del document publicat a:
It is part of: Gut, 2021, vol. 70, num. 12, p. 2283-2296
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Appears in Collections:Publicacions de projectes de recerca finançats per la UE
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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