Microbial metabolites tune amygdala neuronal hyperexcitability and anxiety-linked behaviors

Alterations in gut microbiota composition have been associated with anxiety behaviors in rodents, but the neural mechanisms connecting microbiota and their metabolites to anxiety are not yet understood. The immediate early c-Fos gene expression in the basolateral amygdala (BLA) significantly increased in male C57BL/6J germ-free (GF) mice in this study by Yu et al. (2025), which were not exposed to live microorganisms. These mice also had elevated anxiety behaviors. Higher spontaneous synaptic activity and intrinsic excitability in BLA pyramidal neurons paralleled this rise, and both were associated with a reduction in small conductance calcium-activated potassium (SK) channel currents. SK channel activity in BLA pyramidal neurons was restored, and anxiety behavior was decreased in GF mice colonized with live microorganisms or the metabolite indoles produced from bacteria (Indoles are natural compounds found in cruciferous vegetables and produced by gut bacteria, helping with hormone balance, gut health, and inflammation, and may even protect against cancer and support brain function). These findings support a molecular mechanism where microbes or microbial-derived indoles regulate functional changes in BLA neurons, linking this microbial regulation of anxiety to evolutionarily conserved defense mechanisms in mammals. [NPID: Gut microbiota, anxiety behavior, neural circuitry, basolateral amygdala, c-Fos gene, pyramidal neurons, indoles, microbial metabolites]

Year: 2025

Reference: Yu, W., Xiao, Y., Jayaraman, A., Yen, Y.-C., Lee, H. U., Pettersson, S., & Je, H. S. (2025). Microbial metabolites tune amygdala neuronal hyperexcitability and anxiety-linked behaviors. EMBO Molecular Medicine, 17(2), 249–264. https://doi.org/10.1038/s44321-024-00179-y

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