PT  - JOURNAL ARTICLE
AU  - Arnoriaga-Rodríguez, María
AU  - Mayneris-Perxachs, Jordi
AU  - Contreras-Rodríguez, Oren
AU  - Burokas, Aurelijus
AU  - Ortega-Sanchez, Juan-Antonio
AU  - Blasco, Gerard
AU  - Coll, Claudia
AU  - Biarnés, Carles
AU  - Castells-Nobau, Anna
AU  - Puig, Josep
AU  - Garre-Olmo, Josep
AU  - Ramos, Rafel
AU  - Pedraza, Salvador
AU  - Brugada, Ramon
AU  - Vilanova, Joan C
AU  - Serena, Joaquín
AU  - Barretina, Jordi
AU  - Gich, Jordi
AU  - Pérez-Brocal, Vicente
AU  - Moya, Andrés
AU  - Fernández-Real, Xavier
AU  - Ramio-Torrentà, Lluis
AU  - Pamplona, Reinald
AU  - Sol, Joaquim
AU  - Jové, Mariona
AU  - Ricart, Wifredo
AU  - Portero-Otin, Manuel
AU  - Maldonado, Rafael
AU  - Fernández-Real, Jose Manuel
TI  - Obesity-associated deficits in inhibitory control are phenocopied to mice through gut microbiota changes in one-carbon and aromatic amino acids metabolic pathways
AID  - 10.1136/gutjnl-2020-323371
DP  - 2021 Dec 01
TA  - Gut
PG  - 2283--2296
VI  - 70
IP  - 12
4099  - http://gut.bmj.com/content/70/12/2283.short
4100  - http://gut.bmj.com/content/70/12/2283.full
SO  - Gut2021 Dec 01; 70
AB  - 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.All data relevant to the study are included in the article or uploaded as supplementary information.