Engineering microbial metabolites to modulate tumor immunity and advance cancer immunotherapy

The gut microbiome’s capacity to produce immunomodulatory metabolites is increasingly recognized as a potent determinant of cancer immunotherapy outcomes. This review uniquely integrates emerging data on engineered microbial metabolite production—through synthetic biology, dietary modulation, rational probiotics, and postbiotic therapies—and maps their clinical translation as immunotherapeutic agents. We critically analyze short-chain fatty acids, tryptophan metabolites, bile acids, and polyamines, highlighting their context-specific immune effects and biomarker potential. Moreover, we outline innovative engineering strategies, precision microbiome tools, and personalized therapeutic platforms that reposition microbial metabolites as programmable bioactive drugs. This synthesis aims to guide the next phase of clinical application and regulatory development in microbiome-informed oncology.