Metabolites as potential tools for the diagnosis and treatment of saccular intracranial aneurysms

Intracranial aneurysms (IAs) represent a high-risk cerebrovascular disorder that may lead to fatal subarachnoid haemorrhage. The mechanisms underlying IA formation and rupture remain incompletely elucidated, hindering early diagnosis and effective therapeutic interventions. Emerging evidence has demonstrated that metabolic alteration plays a pivotal role in the development of IAs. This review aims to summarize key metabolites that change in IAs, clarify their mechanistic roles in IAs, and propose new therapeutic strategies based on the understanding of the metabolites for IA management. Metabolic alterations in IAs primarily involve the metabolic pathways of unsaturated fatty acids, taurine, bile acids, tryptophan, and phenylalanine. These metabolites influence IA initiation and progression by modulating critical processes such as inflammation, vascular smooth muscle cell (VSMC) phenotypic switching, and extracellular matrix (ECM) remodelling. Certain metabolites (e.g., oleic acid and arachidonic acid) serve as predictive biomarkers for IAs, while others (e.g., taurine and oleic acid) exhibit therapeutic effects in preclinical IA models. Furthermore, metabolome-based insights have facilitated the exploration of innovative IA treatment strategies, such as dietary interventions, physical exercise, and probiotic/prebiotic supplementation. Metabolites not only serve as potential biomarkers for IA but also provide a foundation for developing metabolism-targeted therapeutic approaches. We need to have a solid understanding of these potential mechanisms to pave the way for therapeutic approaches targeting metabolites for IAs.