Caudovirales bacteriophages are associated with improved executive function and memory in flies, mice, and humans

Mayneris Perxachs, Jordi; Castells-Nobau, Anna; Arnoriaga Rodríguez, María; Garre-Olmo, Josep; Puig, Josep; Ramos, Rafel; Martínez Hernández, Francisco; Burokas, Aurelijus, 1982-; Coll, Clàudia; Moreno-Navarrete, José Maria; Zapata-Tona, Cristina; Pedraza, Salvador; Pérez Brocal, Vicente; Ramió-Torrentà, Lluís; Ricart, Wifredo; Moya, Andrés; Martínez García, Manuel; Maldonado, Rafael, 1961-; Fernández Real, Jose M.

doi:http://dx.doi.org/10.1016/j.chom.2022.01.013

Caudovirales bacteriophages are associated with improved executive function and memory in flies, mice, and humans

Citation

Mayneris-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.2022.01.013

Abstract

Growing 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.