RT Journal Article
SR Electronic
T1 Obesity-associated deficits in inhibitory control are phenocopied to mice through gut microbiota changes in one-carbon and aromatic amino acids metabolic pathways
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 2283
OP 2296
DO 10.1136/gutjnl-2020-323371
VO 70
IS 12
A1 María Arnoriaga-Rodríguez
A1 Jordi Mayneris-Perxachs
A1 Oren Contreras-Rodríguez
A1 Aurelijus Burokas
A1 Juan-Antonio Ortega-Sanchez
A1 Gerard Blasco
A1 Claudia Coll
A1 Carles Biarnés
A1 Anna Castells-Nobau
A1 Josep Puig
A1 Josep Garre-Olmo
A1 Rafel Ramos
A1 Salvador Pedraza
A1 Ramon Brugada
A1 Joan C Vilanova
A1 Joaquín Serena
A1 Jordi Barretina
A1 Jordi Gich
A1 Vicente Pérez-Brocal
A1 Andrés Moya
A1 Xavier Fernández-Real
A1 Lluis Ramio-Torrentà
A1 Reinald Pamplona
A1 Joaquim Sol
A1 Mariona Jové
A1 Wifredo Ricart
A1 Manuel Portero-Otin
A1 Rafael Maldonado
A1 Jose Manuel Fernández-Real
YR 2021
UL http://gut.bmj.com/content/70/12/2283.abstract
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.