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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Detalhes bibliográficos
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 documento: artigo
Estado:Versão publicada
Data de publicação:2021
País:España
Recursos:Universitat de Lleida (UdL)
Repositório:Repositori Obert UdL
OAI Identifier:oai:repositori.udl.cat:10459.1/71488
Acesso em linha:https://doi.org/10.1136/gutjnl-2020-323371
http://hdl.handle.net/10459.1/71488
Access Level:Acceso aberto
Palavra-chave:Intestinal microbiology
Obesity
Descrição
Resumo: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.

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