Metabolic interactions of host-gut microbiota: Shaping the future of precision diagnosis and therapeutic discovery in gastrointestinal cancers

This collection of reviews and research articles highlights the diagnostic and therapeutic potential of gut microbial metabolites across various gastrointestinal cancers, including but not limited to hepatobiliary and pancreatic cancers, gastric cancer, and cholangiocarcinoma. Numerous gut microbial metabolites have been observed to mechanistically regulate cancer cell proliferation and development, supporting their utility as molecular biomarkers for clinical diagnosis and as targets for precision interventions. However, most functional metabolites derived from both host cancer tissues and the gut microbiota remain structurally unidentified; their functional features are largely unexplored due to limitations in conventional measurement technologies. To address these challenges, we propose a transformative functional metabolomics approach-S2M2ART (Single-Cell Spatial Metabolomics Metagenomics-Artificial Intelligence Recombinational Toolkit)-which will leverage AI-powered multimodal omics and single-cell, spatially-resolved analyses to decode the molecular functions and mechanisms of these metabolites in gastrointestinal cancer development. Collectively, this innovative technique will substantially enhance the applicability and translational potential of microbial metabolites in gastrointestinal cancers and beyond.