Multiple omics reveal link between the microbiota-gut-brain axis and intracranial aneurysm rupture

Intracranial aneurysms (IAs) are benign cerebrovascular maladies characterized by pathological dilatation in the walls of intracranial arteries. However, spontaneous subarachnoid hemorrhage (SAH) resulting from aneurysm rupture poses a grave threat to the patient's life. Accumulating evidence implicates gut ecological dysregulation in the pathogenesis of IAs. Nevertheless, the relevance of gut dysbiosis to the rupture of IAs remains unknown. In this study, altogether 124 fecal samples were employed for microbiome sequencing by third-generation 16s rRNA sequencing, while 160 fecal samples were sequenced for metabolomics sequencing by liquid chromatography-mass spectroscopy techniques. Furthermore, the stool samples from IAs and healthy family controls were partitioned into two cohorts: the discovery set and the validation set for mutual cross-validation. Differential gut microbiota and metabolites associated with ruptured intracranial aneurysms (RIAs) were identified. Additionally, a superior risk assessment model for RIAs was constructed utilizing these differential species and metabolites. Subsequent integrated metabolomics and microbiomics analyses have uncovered a profound link between the dysregulation of unsaturated fatty acid and essential amino acid metabolic pathways and the rupture of IAs. This metabolic imbalance is attributed to alternations in the gut microbiota composition. Furthermore, we further revealed alterations in the gut flora of patients with IAs at high-risk rupture locations, incorporating the clinical characteristics. Finally, 30 peripheral blood and paired cerebrospinal fluid samples were tested to confirm variations in α-linolenic acid, linoleic acid and butyric acid concentrations among IA patients. This study underscores the crucial role of gut microbiota and metabolisms dysbiosis in IAs formation, while also highlighting a novel risk factor for aneurysm rupture. The identification and validation of differential species and metabolites provide new assessment biomarkers against IAs rupture.