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Updated: Jul 9, 2025
Intracerebroventricular Delivery of Gut-Derived Microbial Metabolites in Freely Moving Mice
Published on: June 2, 2022
Infant gut microbiota contributes to cognitive performance in mice
Tomás Cerdó1, Alicia Ruiz-Rodríguez2, Inmaculada Acuña3
1Maimonides 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.
Insights
The infant gut microbiome composition influences cognitive development by 6 months. Specific gut bacteria and their metabolites, like histidine, are linked to higher cognitive function, suggesting a causative role.
Area of Science:
- Microbiology
- Neuroscience
- Metabolomics
Background:
- The gut microbiota plays a crucial role in infant neurodevelopment.
- Early life gut microbiome composition is increasingly recognized as a factor influencing cognitive outcomes.
Purpose of the Study:
- To establish a link between infant composite cognition and gut microbiota composition at 6 months.
- To investigate the role of specific microbial metabolites, such as histidine, in infant cognition.
Main Methods:
- Analysis of gut microbiota composition, diversity, and evenness in infants.
- Metaproteomic and metabolomic analyses to identify microbial-metabolite-cognition associations.
- Fecal microbiota transplantation into germ-free mice to assess the transmissibility of cognitive traits.
Main Results:
- Infants with higher composite cognition exhibited greater gut microbial diversity and evenness.
- Microbial histidine ammonia lyase and infant histidine metabolism were associated with cognition.
- Fecal transplantation demonstrated that cognitive traits, including memory, are transmissible via gut microbiota.
- Specific bacterial species (Phocaeicola, Bacteroides, Bifidobacterium) and altered histidine metabolite levels were linked to enhanced cognition in mice.
Conclusions:
- The gut microbiota plays a causative role in infant cognitive development.
- Modulation of histidine metabolite levels by the gut microbiota is a potential mechanism underlying this effect.
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.
