Microbiome signatures of diagnosis and aggressiveness of a neurovascular disease, cavernous angioma

Cavernous angiomas (CA) also known as cerebral cavernous malformation (CCM) are common vascular anomalies causing brain hemorrhage1,2. While the genetics of CA are relatively well understood, factors mediating lesion development and clinical manifestations are not clear. Based on mouse studies, roles of gram-negative bacteria and altered intestinal homeostasis have been implicated in CA pathogenesis3. We assessed microbiome differences in patients with and without CA, and among CA subjects with different clinical features. We showed that CA patients have distinct microbiome signatures consistent with postulated mechanisms driving lesion genesis. Other microbiome differences are related to CA clinical behavior. Weighted combinations of microbiome signatures and plasma inflammatory biomarkers enhance associations with disease severity and hemorrhage. Our investigation of the CA-associated microbiome will guide future mechanistic studies of CA pathogenesis and demonstrates how the microbiome may be used as a biomarker of disease severity and clinical course in a neurovascular disease.