Gut Microbiota-Host Redox Crosstalk: Molecular Mechanisms, Disease Pathogenesis, and Therapeutic Interventions

The crosstalk between the gut microbiota and the host redox system is essential for maintaining intestinal homeostasis and systemic health. Disruption of this bidirectional interaction impairs redox balance, promotes oxidative stress, and contributes to the initiation and progression of a wide range of diseases, including inflammatory bowel disease, metabolic liver disease, neurodegenerative disorders, and chronic kidney disease. In this review, we comprehensively summarize the molecular mechanisms by which the gut microbiota regulates host redox homeostasis, focusing on microbial metabolites, immune signaling, and host antioxidant pathways. We also discuss emerging mechanisms underlying microbiota-host redox interactions, including extracellular vesicle (EV)-mediated interkingdom communication, microbiota-driven regulation of intestinal epithelial ferroptosis, and microbial metabolic reprogramming. Furthermore, we highlight how gut microbiota dysbiosis extends oxidative stress beyond the intestine through the gut-liver, gut-brain, and gut-kidney axes, thereby driving the development of multiple organ diseases. Finally, we summarize recent advances in microbiota-targeted therapies and engineered bacterial EVs as innovative strategies for restoring redox homeostasis, and discuss their potential for the precision prevention and treatment of oxidative stress-associated diseases as well as the development of next-generation microbiome-based therapeutics.