Microbial metabolites tune amygdala neuronal hyperexcitability and anxiety-linked behaviors

The correlation between gut microbiota composition and anxiety behavior

This research investigates the correlation between gut microbiota composition and anxiety behavior, with a particular focus on the neural mechanisms involved. In male C57BL/6J germ-free (GF) mice, an increase in anxiety-related behaviors was observed, which correlated with elevated expression of the immediate early c-Fos gene in the basolateral amygdala (BLA). This increase was accompanied by heightened intrinsic excitability and spontaneous synaptic activity in BLA pyramidal neurons, attributed to diminished small conductance calcium-activated potassium (SK) channel currents. Furthermore, colonization of GF mice with live microbes or administration of the microbial-derived metabolite indoles reversed the alterations in SK channel activity, subsequently reducing anxiety behaviors. These findings suggest a molecular mechanism through which gut microbiota and their metabolites influence neuronal function in the BLA, linking microbial regulation to evolutionary conserved defense mechanisms related to anxiety in mammals. [NPID: Microbiota, anxiety, basolateral amygdala, metabolites, germ-free, metabolite indoles]

Year: 2025

Reference: Rehman, S. S. U., Nasar, M. I., Mesquita, C. S., Al Khodor, S., Notebaart, R. A., Ott, S., Mundra, S., Arasardanam, R. P., Muhammad, K., & Alam, M. T. (2025). Integrative systems biology approaches for analyzing microbiome dysbiosis and species interactions. Briefings in Bioinformatics, 26(4), bbaf323. https://doi.org/10.1093/bib/bbaf323