Gut microbiota-derived 5-hydroxyindole-3-acetic acid mediates the anti-colitis effect of Phellinus gilvus in mice

Abstract Background: The gut microbiota plays crucial roles in various diseases and mediates the therapeutic effect of many drugs. Results: In this study, we found that ingestion of Phellinus gilvus extract (SH), a traditional Chinese medical mushroom, effectively ameliorated dextran sodium sulfate (DSS)-induced colits in mice, and the gut microbes were essential for its therapeutic effect. The enrichment of Alistipes spp. especially A. onderdonkii was highly associated with the amelioration of colitis by SH, and oral gavage of live A. onderdonkii potently and strain-specifically mitigated DSS-induced colitis in mice. 5-Hydroxyindole-3-acetic acid (5HIAA), a structural analogue of a known aromatic hydrocarbon receptor (AhR) activator indole-3-acetic acid (IAA), was significantly enriched after SH treatment and exhibited more potent anti-colitis efficiency than IAA in mice.Conclusion: Our results demonstrated the gut microbiota-derived 5HIAA could be an effective candidate in treatment of colitis, and modulation of the gut microbiota-indole derives-AhR pathway may be a novel strategy in development of next-generational anti-colitis drugs.