Infant gut microbiota contributes to cognitive performance in mice Cerdó, Tomás Ruiz Rodríguez, Alicia Acuña Morales, Inmaculada Torres Espínola, Francisco José Menchén Márquez, Sergio Gámiz Ruiz, Fernando Gallo Torre, Milagros Jehmlich, Nico Haange, Sven-Bastiaan Von Bergen, Martin Campoy Folgoso, Cristina Suárez García, Antonio Francisco Cognition Germ-free mice Gut Histidine metabolome Infant Microbiota Metaproteomics Work in the author’s laboratories was performed on resources provided by the Spanish Health and Science Ministries (PREOBE project P06-CTS-02341, BFU2012-40254-C03-01, and PID2020-114269GB-I00), Junta de Andalucía, and UFZ-Germany. T.C. participated in the PhD program in biomedicine at UGR, was a fellowship of the FPI program (BES-2013-065133) funded by the Spanish Ministry of Economy and Competitiveness, and is currently supported by the ‘‘Sara Borrell’’ program (CD21/00187) of the Carlos III Institute. I.A., S.M.-M., and A.R.-R. were granted PhD scholarships (FPU) from the Spanish Ministry of Economy and Competitiveness. A.R.-R. currently holds a María Zambrano Next Generation EU-Talent Reincorporation from UGR. Gut microbiota has been related to infant neurodevelopment. Here, an association between infant composite cognition with gut microbiota composition was established as soon as 6 months. Higher diversity and evenness characterized microbial communities of infants with composite cognition above (Inf-aboveCC) versus below (Inf-belowCC) median values. Metaproteomic and metabolomic analyses established an association between microbial histidine ammonia lyase activity and infant histidine metabolome with cognition. Fecal transplantation from Inf-aboveCC versus Inf-belowCC donors into germ-free mice showed that memory, assessed by novel object recognition test, was a transmissible trait. Furthermore, Inf-aboveCC mice were enriched in species previously linked to cognition belonging to Bacteroides, Phaeicola and Bifidobacterium. Finally, Inf-aboveCC mice showed differential faecal histidine, hippocampal urocanate and histidine-urocanate-glutamate ratios compared to Inf-aboveCC mice. Overall, these findings reveal a causative role of gut microbiota on infant cognition pointing at modulation of histidine metabolite levels as a potential underlying mechanism. 2024-01-12T13:33:57Z 2024-01-12T13:33:57Z 2023 journal article Published version: Cerdó, Tomás et al. Infant gut microbiota contributes to cognitive performance in mice. Cell Host Microbe. 2023. Dec 13;31(12):1974-1988.e4. [doi: 10.1016/j.chom.2023.11.004] https://hdl.handle.net/10481/86758 10.1016/j.chom.2023.11.004 eng http://creativecommons.org/licenses/by-nc-nd/4.0/ open access Attribution-NonCommercial-NoDerivatives 4.0 Internacional