The Interplay between Gut Microbiota-Derived Metabolites and Ferroptosis: Implications for Intestinal Health and Disease

Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation (LPO), has emerged as a critical player in intestinal health and disease. The gut microbiota, through metabolic activity, generate bioactive metabolites that influence host physiology, including the regulation of ferroptosis. Recent studies have highlighted the pivotal role of gut microbiota-derived metabolites in sustaining intestinal homeostasis. Although the human body has evolved natural mechanisms, such as ferroptosis, to maintain gut equilibrium, elucidating the contribution of gut microbiota-derived metabolites to this process remains a critical area of research. This Review systematically examines the molecular mechanisms underlying ferroptosis, the interplay between gut microbial metabolites and ferroptotic pathways, and the implications for intestinal disorders. Furthermore, it explores innovative therapeutic strategies targeting microbial metabolite-ferroptosis interactions. By synthesizing current evidence, this work aims to advance the development of microbiota-centric therapies for ferroptosis-related intestinal pathologies, bridging mechanistic insights with translational potential.