Mayneris Perxachs, JordiCastells-Nobau, AnnaArnoriaga Rodríguez, MaríaGarre-Olmo, JosepPuig, JosepRamos, RafelMartínez Hernández, FranciscoBurokas, Aurelijus, 1982-Coll, ClàudiaMoreno-Navarrete, José MariaZapata-Tona, CristinaPedraza, SalvadorPérez Brocal, VicenteRamió-Torrentà, LluísRicart, WifredoMoya, AndrésMartínez García, ManuelMaldonado, Rafael, 1961-Fernández Real, Jose M.2022-04-252022-04-252022Mayneris-Perxachs J, Castells-Nobau A, Arnoriaga-Rodríguez M, Garre-Olmo J, Puig J, Ramos R, Martínez-Hernández F, Burokas A, Coll C, Moreno-Navarrete JM, Zapata-Tona C, Pedraza S, Pérez-Brocal V, Ramió-Torrentà L, Ricart W, Moya A, Martínez-García M, Maldonado R, Fernández-Real JM. Caudovirales bacteriophages are associated with improved executive function and memory in flies, mice, and humans. Cell Host Microbe. 2022 Mar 9;30(3):340-56.e8. DOI: 10.1016/j.chom.2022.01.0131931-3128http://hdl.handle.net/10230/52878Growing evidence implicates the gut microbiome in cognition. Viruses, the most abundant life entities on the planet, are a commonly overlooked component of the gut virome, dominated by the Caudovirales and Microviridae bacteriophages. Here, we show in a discovery (n = 114) and a validation cohort (n = 942) that subjects with increased Caudovirales and Siphoviridae levels in the gut microbiome had better performance in executive processes and verbal memory. Conversely, increased Microviridae levels were linked to a greater impairment in executive abilities. Microbiota transplantation from human donors with increased specific Caudovirales (>90% from the Siphoviridae family) levels led to increased scores in the novel object recognition test in mice and up-regulated memory-promoting immediate early genes in the prefrontal cortex. Supplementation of the Drosophila diet with the 936 group of lactococcal Siphoviridae bacteriophages resulted in increased memory scores and upregulation of memory-involved brain genes. Thus, bacteriophages warrant consideration as novel actors in the microbiome-brain axis.application/pdfeng© 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).info:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.chom.2022.01.013DrosophilaBacteriophagesBrainCognitionFecal transplantationHumanMemoryMiceMicrobiomeinfo:eu-repo/semantics/openAccess