Astragalus Membranaceus Ameliorates Chemotherapy-Induced Intestinal Mucositis Via Gut Microbiota-Related Innate Immunity and Amino Acid Metabolites

Astragalus membranaceus is a widely utilized medicinal and edible herb, serving as immunostimulant, metabolic regulator, anticancer agent, and hepatoprotectant agent. However, its protective effect against chemotherapy-induced intestinal mucositis (CIM) remains poorly elucidated. The study aimed to investigate the therapeutic efficacy and mechanism of Astragalus membranaceus extract (AME) in alleviating CIM using Drosophila melanogaster and C57BL/6J mouse models. The mechanisms of AME were evaluated via multi-omics approaches, including transcriptomic profiling, 16 S rRNA sequencing, and targeted metabolomics. The expression levels of the TLR4/NF-κB pathway and glutathione metabolic pathway were analyzed by RT-qPCR and immunofluorescence. AME supplementation significantly mitigated CPT-11-induced systemic and intestinal damage in adult flies and mice. Mechanistically, AME markedly down-regulated the TLR4/NF-κB pathway and up-regulated glutathione metabolism. AME also modulated gut microbiota composition, increased relative abundance of Lactobacillus, unidentified_Lachnospiraceae, and Ruminococcus, and decreased abundance of Streptococcus, Bacteroides, and Alistipes. Meanwhile, AME decreased the levels of glutamine (Gln), lysine (Lys), phenylalanine (Phe), proline (Pro), and valine (Val), while increasing threonine (Thr). In conclusion, AME alleviates CIM via regulating gut microbiota-related innate immunity and amino acid metabolism.