Moreover, oral supplementation with IAA replicated the antidepressant effects of SNS and suppressed CUMS-induced neuroinflammation via the AhR/NF-κB signaling pathway.<h4>Conclusion</h4>SNS alleviates depression-like behavior by modulating gut microbiota-mediated tryptophan metabolism to enhance IAA production, thereby activating central AhR signaling and suppressing NF-κB-mediated neuroinflammation. The gene discussed is NFKB1; the disease is major depressive disorder.