Infant gut microbiota contributes to cognitive performance in mice

Tomás Cerdó; Alicia Ruiz-Rodríguez; Inmaculada Acuña; Francisco José Torres-Espínola; Sergio Menchén-Márquez; Fernando Gámiz; Milagros Gallo; Nico Jehmlich; Sven-Bastiaan Haange; Martin von Bergen; Cristina Campoy; Antonio Suárez

doi:10.1016/j.chom.2023.11.004

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. Epub 2023 Dec 4.

Affiliations

¹ Maimonides Biomedical Research Institute of Córdoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, 14004 Córdoba, Spain; Centre for Rheumatology Research, Division of Medicine, University College London, London WC1E 6JF, UK.
² Department of Biochemistry and Molecular Biology 2, Nutrition and Food Technology Institute "José Mataix" (INYTA), Biomedical Research Centre (CIBM), University of Granada, 18016 Granada, Spain; Department of Microbiology, Nutrition and Food Technology Institute "José Mataix" (INYTA), Biomedical Research Centre (CIBM), University of Granada, 18016 Granada, Spain. Electronic address: aliruizrodriguez@ugr.es.
³ Department of Biochemistry and Molecular Biology 2, Nutrition and Food Technology Institute "José Mataix" (INYTA), Biomedical Research Centre (CIBM), University of Granada, 18016 Granada, Spain.
⁴ EURISTIKOS Excellence Centre for Pediatric Research, Institute of Neurosciences, Biomedical Research Centre (CIBM), University of Granada, 18016 Granada, Spain.
⁵ Department of Psychobiology, Institute of Neurosciences, Biomedical Research Centre (CIBM), University of Granada, 18016 Granada, Spain.
⁶ Department of Psychobiology, Institute of Neurosciences, Biomedical Research Centre (CIBM), University of Granada, 18016 Granada, Spain; Instituto de Investigación Biosanitaria (IBS), 18014 Granada, Spain.
⁷ Department of Molecular System Biology, Helmholtz Centre for Environmental Research-UFZ, Permoserstraße 15, 04318 Leipzig, Germany.
⁸ EURISTIKOS Excellence Centre for Pediatric Research, Institute of Neurosciences, Biomedical Research Centre (CIBM), University of Granada, 18016 Granada, Spain; Instituto de Investigación Biosanitaria (IBS), 18014 Granada, Spain; Department of Pediatrics, School of Medicine, University of Granada, 18016 Granada, Spain.

PMID: 38052208
DOI: 10.1016/j.chom.2023.11.004

Abstract

Gut microbiota has been linked to infant neurodevelopment. Here, an association between infant composite cognition and gut microbiota composition is established as soon as 6 months. Higher diversity and evenness characterize microbial communities of infants with composite cognition above (Inf-aboveCC) versus below (Inf-belowCC) median values. Metaproteomic and metabolomic analyses establish an association between microbial histidine ammonia lyase and infant histidine metabolome with cognition. Fecal transplantation from Inf-aboveCC versus Inf-belowCC donors into germ-free mice shows that memory, assessed by a novel object recognition test, is a transmissible trait. Furthermore, Inf-aboveCC mice are enriched in species belonging to Phocaeicola, as well as Bacteroides and Bifidobacterium, previously linked to cognition. Finally, Inf-aboveCC mice show lower fecal histidine and urocanate:histidine and urocanate:glutamate ratios in the perirhinal cortex compared to Inf-belowCC mice. Overall, these findings reveal a causative role of gut microbiota on infant cognition, pointing at the modulation of histidine metabolite levels as a potential underlying mechanism.

Keywords: cognition; germ-free mice; gut; histidine metabolome; infant; metaproteomics; microbiota.

MeSH terms

Animals
Fecal Microbiota Transplantation
Feces / microbiology
Gastrointestinal Microbiome*
Histidine
Humans
Infant
Mice
Microbiota*

Substances

Histidine