Polysaccharide A1 from Bran-Fried Atractylodes lancea Regulates Cyclophosphamide-induced Intestinal Immune Injury in Mice via the Faecalibaculum rodentium -Mediated IAA-AHR/RORC Axis

Cyclophosphamide-induced intestinal injury is often characterized by gut microbiota dysbiosis and metabolite imbalance. Bran-fried Atractylodes lancea polysaccharide (FALP-A1) protects against cyclophosphamide-induced intestinal injury by significantly modulating Faecalibaculum rodentium abundance. However, the mechanism of FALP-A1-mediated F. rodentium regulation remains unclear. Ex vivo digestion confirmed FALP-A1 is stable in the simulated upper gastrointestinal tract, while fermentation showed it is degradable and enriches F. rodentium. Nontargeted fecal metabolomics of in vivo mice co-treated with the FALP-A1 and Faecalibaculum rodentium, together with ex vivo coculture systems, identified Indoleacetic acid (IAA) as a potential metabolite. We further validated that IAA protects the intestinal barrier in cyclophosphamide-induced intestinal injury by modulating nuclear transcription factor RORC mRNA expression. However, these effects were reversed by an AHR inhibitor. This study elucidates the central role of “FALP-A1-F. rodentium-IAA-AHR/RORC” axis in protecting against cyclophosphamide-induced intestinal injury, providing evidence for pharmacological potential of FALP-A1 and indole-3-acetic acid.