The indole-brain connection: neuroimmune mechanisms and therapy

Dec 12, 2025Current opinion in immunology

The link between indole compounds and the brain: immune-related processes and potential treatments

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Abstract

Microbiota-derived metabolites, particularly indole and its derivatives, are emerging as critical factors in the microbiota-gut-brain axis.

  • Indole and its derivatives influence communication between the gut and brain through immune, neural, and endocrine pathways.
  • These metabolites activate the aryl hydrocarbon receptor (AhR), which modulates neuroimmune responses.
  • Regulation of microglial activation, astrocyte reactivity, and blood-brain barrier integrity is associated with indole-derived metabolites.
  • Effects on neuroinflammation, nerve regeneration, and blood-brain barrier function have been observed in animal studies.
  • Challenges remain in translating findings to clinical settings due to conditional effects of AhR signaling and difficulties in gut metabolite delivery.

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