Gut microbial metabolism via hippocampal indole-AhR signaling regulates emotional symptoms

Reduced gut microbiota-derived indole is associated with emotional modulation through the hippocampal aryl hydrocarbon receptor.

• A decrease in the abundance of Alistipes shahii leads to lower intestinal indole levels due to a loss of tryptophanase in irritable bowel syndrome (IBS) patients and model mice.
• Indole interacts with the aryl hydrocarbon receptor (AhR) in the brain, particularly in the ventral dentate gyrus, which plays a crucial role in emotion regulation.
• Lower levels of indole result in diminished nuclear AhR expression and reduced activity of granule cells in the ventral dentate gyrus, which is linked to affective symptoms.
• Transplantation of tryptophanase-producing microbiota, supplementation with indole or tryptophanase, activation of ventral dentate gyrus neurons, or administration of diosmin can alleviate emotional symptoms in IBS mice.
• These findings highlight the Alistipes shahii-tryptophanase-indole-AhR-vDG pathway as a potential gut-brain axis involved in affective disturbances.

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