Permissive microbiome characterizes human subjects with a neurovascular disease cavernous angioma
Open Access
- 27 May 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 11 (1), 1-11
- https://doi.org/10.1038/s41467-020-16436-w
Abstract
Cavernous angiomas (CA) are common vascular anomalies causing brain hemorrhage. Based on mouse studies, roles of gram-negative bacteria and altered intestinal homeostasis have been implicated in CA pathogenesis, and pilot study had suggested potential microbiome differences between non-CA and CA individuals based on 16S rRNA gene sequencing. We here assess microbiome differences in a larger cohort of human subjects with and without CA, and among subjects with different clinical features, and conduct more definitive microbial analyses using metagenomic shotgun sequencing. Relative abundance of distinct bacterial species in CA patients is shown, consistent with postulated permissive microbiome driving CA lesion genesis via lipopolysaccharide signaling, in humans as in mice. 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. This is the first demonstration of a sensitive and specific diagnostic microbiome in a human neurovascular disease.Funding Information
- U.S. Department of Health & Human Services | National Institutes of Health (F30NS100252, U54 NS065705, U54 NS065705, U54 NS065705, U54 NS065705, P01 NS092521, R01 NS100949, R01 HL094326, UL1 TR001863, P01 NS092521, R01 NS100949, UL1 TR001863)
- U.S. Department of Health & Human Services | National Institutes of Health
- U.S. Department of Health & Human Services | National Institutes of Health
- U.S. Department of Health & Human Services | National Institutes of Health
- U.S. Department of Health & Human Services | National Institutes of Health
- U.S. Department of Health & Human Services | National Institutes of Health
- U.S. Department of Health & Human Services | National Institutes of Health
- U.S. Department of Health & Human Services | National Institutes of Health
- U.S. Department of Health & Human Services | National Institutes of Health
- U.S. Department of Defense (W81XWH-18-1-0501)
- U.S. Department of Health & Human Services | National Institutes of Health
- U.S. Department of Health & Human Services | National Institutes of Health
- U.S. Department of Health & Human Services | National Institutes of Health
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