Noncanonical Roles of Metabolites in Disease Progression and Precision Medicine

Metabolites are small molecules produced by biochemical reactions in living organisms and serve as the material foundation for life activities. Conventionally, metabolites have been regarded primarily as energy substrates and biosynthetic precursors for macromolecules. Beyond these roles, accumulating evidence has shown that metabolites also function as key regulators of diverse signaling events through noncanonical mechanisms, including epigenetic regulation, post-translational modifications, and intercellular communication. Importantly, aberrant alterations in metabolites are closely linked to the onset and progression of various diseases, such as neurodegenerative diseases, cancer, and autoimmune disorders, where metabolic reprogramming drives pathological remodeling of the tissue microenvironment. On this basis, researchers have developed various therapeutic strategies to target metabolic disturbances and restore metabolic balance, including lifestyle interventions, bioactive compound supplementation, and pharmacological treatments. Accordingly, this review systematically discusses the network architecture and interconnections of the three core metabolic pathways, highlights the roles of specific metabolites in disease pathogenesis, and offers insights into potential therapeutic approaches.