The Gut Microbiota–Ferroptosis Axis: Emerging Perspectives in Gastrointestinal Tumorigenesis and Progression

In recent years, the relationship between the gut microbiota and gastrointestinal tumors has become a growing focus in tumor biology research. Ferroptosis, an iron-dependent form of programmed cell death, serves as a crucial link mediating the interaction between the two. This review begins by clarifying the intricate connections among the gut microbiota, ferroptosis, and gastrointestinal tumors. It then systematically summarizes the mediating role of ferroptosis, focusing on iron metabolism, lipid peroxidation, and amino acid metabolism, in facilitating host-microbiota interactions. From a metabolic standpoint, particular emphasis is placed on how the gut microbiota affects ferroptosis in various gastrointestinal tumors, including gastric, pancreatic, liver, and colorectal tumors, through the use of metabolites such as lipopolysaccharides (LPSs), short-chain fatty acids (SCFAs), bile acids (BAs), vitamins, glutamine (Gln), and tryptophan derivatives. A deeper understanding of this complex regulatory network reveals new mechanisms for the development and progression of digestive tract tumors. This insight could inform the development of novel therapeutic strategies targeting the gut microbiota-ferroptosis axis. Additionally, these findings point to the potential clinical value of pursuing this research direction.