ArticleEMBO molecular medicine2025
Microbial metabolites tune amygdala neuronal hyperexcitability and anxiety-linked behaviors.
Article in EMBO molecular medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Novel insight into the effects of the metabolites from gut microbiota in both unmedicated depressive adolescents and mice: key roles of indole derivatives-aryl hydrocarbon receptor signaling in neurogenesis and microglial homeostasis.Molecular psychiatry · 2026Article
- Integrative metabolomics and machine learning identify biomarkers of adolescent social anxiety disorder.World journal of pediatrics : WJP · 2026Article
- The maternal gut-fetal brain axis: role of maternal microbial metabolome in early neurodevelopment.Frontiers in nutrition · 2026Review
- The bridging role of gut microbiota-derived metabolites in neuropathic pain comorbid with anxiety.Frontiers in neuroscience · 2026Review
- Gut microbiota-derived tryptophan metabolites: molecular mechanisms, nutritional strategies and implications for swine health.Frontiers in veterinary science · 2026Review
- Article
- Integrative systems biology approaches for analyzing microbiome dysbiosis and species interactions.Briefings in bioinformatics · 2025Review
- The Legalome: Microbiology, Omics and Criminal Justice.Microbial biotechnology · 2025Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Changes in gut microbiota composition have been linked to anxiety behavior in rodents. However, the underlying neural circuitry linking microbiota and their metabolites to anxiety behavior remains unknown. Using male C57BL/6J germ-free (GF) mice, not exposed to live microbes, increased anxiety-related behavior was observed correlating with a significant increase in the immediate early c-Fos gene in the basolateral amygdala (BLA). This phenomenon coincided with increased intrinsic excitability and spontaneous synaptic activity of BLA pyramidal neurons associated with reduced small conductance calcium-activated potassium (SK) channel currents. Importantly, colonizing GF mice to live microbes or the microbial-derived metabolite indoles reverted SK channel activities in BLA pyramidal neurons and reduced the anxiety behavioral phenotype. These results are consistent with a molecular mechanism by which microbes and or microbial-derived indoles, regulate functional changes in the BLA neurons. Moreover, this microbe metabolite regulation of anxiety links these results to ancient evolutionarily conserved defense mechanisms associated with anxiety-related behaviors in mammals.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.