PT  - JOURNAL ARTICLE
AU  - María Arnoriaga-Rodríguez
AU  - Jordi Mayneris-Perxachs
AU  - Oren Contreras-Rodríguez
AU  - Aurelijus Burokas
AU  - Juan-Antonio Ortega-Sanchez
AU  - Gerard Blasco
AU  - Claudia Coll
AU  - Carles Biarnés
AU  - Anna Castells-Nobau
AU  - Josep Puig
AU  - Josep Garre-Olmo
AU  - Rafel Ramos
AU  - Salvador Pedraza
AU  - Ramon Brugada
AU  - Joan C Vilanova
AU  - Joaquín Serena
AU  - Jordi Barretina
AU  - Jordi Gich
AU  - Vicente Pérez-Brocal
AU  - Andrés Moya
AU  - Xavier Fernández-Real
AU  - Lluis Ramio-Torrentà
AU  - Reinald Pamplona
AU  - Joaquim Sol
AU  - Mariona Jové
AU  - Wifredo Ricart
AU  - Manuel Portero-Otin
AU  - Rafael Maldonado
AU  - Jose Manuel Fernández-Real
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.