The indole-brain connection: neuroimmune mechanisms and therapy

Area of Science:

• Neuroscience
• Microbiology
• Immunology

Background:

• The microbiota-gut-brain axis (MGBA) is a complex communication network linking the gut and brain.
• Gut microbiota metabolites, particularly indole derivatives from tryptophan, are key regulators of the MGBA.
• These metabolites influence neuroimmune responses and blood-brain barrier (BBB) integrity via the aryl hydrocarbon receptor (AhR).

Purpose of the Study:

• To review recent advancements in the indole-brain connection within the MGBA.
• To critically evaluate current therapeutic strategies targeting this axis.
• To identify challenges and future directions for clinical translation.

Main Methods:

• Literature review of studies on indole, AhR signaling, and the MGBA.
• Analysis of research on neuroinflammation, neuroregeneration, and BBB function.
• Evaluation of preclinical and clinical findings related to indole derivatives.

Main Results:

• Indole derivatives modulate microglial activation, astrocyte reactivity, and BBB integrity through AhR.
• These metabolites impact neuroinflammation and nerve regeneration.
• Animal studies show promise, but clinical application is hindered by AhR signaling variability and delivery issues.

Conclusions:

• The indole-brain connection is crucial for MGBA function, influencing neurological health.
• Targeting indole-mediated AhR signaling offers potential therapeutic avenues for neurological disorders.
• Further research is needed to overcome challenges in clinical translation, including biomarker development and targeted delivery.