Arnoriaga Rodríguez, MaríaBurokas, Aurelijus, 1982-Ortega Sánchez, Juan AntonioMaldonado, Rafael, 1961-Fernández Real, Jose M.2021-03-102021-03-102021Arnoriaga-Rodríguez M, Mayneris-Perxachs J, Contreras-Rodríguez O, Burokas A, Ortega-Sanchez JA, Blasco G et al. Obesity-associated deficits in inhibitory control are phenocopied to mice through gut microbiota changes in one-carbon and aromatic amino acids metabolic pathways. Gut. 2021;70(12):2283-96. DOI: 10.1136/gutjnl-2020-3233710017-5749http://hdl.handle.net/10230/46707Background: 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.application/pdfeng© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. http://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1136/gutjnl-2020-323371Intestinal microbiologyObesityinfo:eu-repo/semantics/openAccess