Precision modulation of the gut microbiota-immune axis by natural products: a structure-activity relationship perspective in cancer immunotherapy

Natural products (NPs) provide a chemically precise strategy to overcome gut dysbiosis-driven resistance in cancer immunotherapy. This review deconstructs how distinct structural determinants of polysaccharides, terpenoids, polyphenols, and alkaloids dictate specific microbial remodeling and immunomodulatory outcomes. These structure-activity relationship (SAR)-driven mechanisms selectively enrich beneficial microbes, modulate metabolites, and reprogram host immune pathways, thereby potentiating diverse immunotherapies and converting "cold" tumors into "hot" ones. Future integration of SAR with AI-driven multi-omics and synthetic biology will enable rational design of next-generation NPs and personalized interventions, offering a promising avenue for more effective and less toxic cancer immunotherapies.