Gut microbiota shape diurnal rhythms of amino acid metabolism in the mouse prefrontal cortex

OBJECTIVES: The gut microbiota plays a key role in maintaining brain health and homeostasis. Previous studies have demonstrated that metabolites in the brain respond to alterations in gut microbial composition. In this study we aimed to explore how depletion of the gut microbiota is associated with alterations in the diurnal rhythmicity of metabolites in the brain. METHODS: We used antibiotic-induced microbial depletion in mice to examine the impact of the gut microbiota on the rhythmicity of metabolites in the prefrontal cortex. Metabolite profiles were assessed across multiple timepoints using untargeted metabolomics. RESULTS: Microbial depletion was associated with alterations in the rhythmic profile of metabolites in the prefrontal cortex, with amino acids showing a robust inversion of their normal rhythm. These alterations were specific to the prefrontal cortex, with hippocampus and amygdala showing minimal changes. This altered gut microbial environment was associated with potential consequences for neurotransmitter production, including glutamate and serotonin. CONCLUSIONS: These findings provide further evidence that the gut microbiota shapes rhythmic diurnal processes in the brain. Future studies are warranted to investigate how such microbial effects influence actual neurotransmitter levels and behavioral phenotypes associated with the prefrontal cortex.