Permissive microbiome characterizes human subjects with a neurovascular disease cavernous angioma
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- May 27, 2020
- Source ID
- 10.1038/s41467-020-16436-w
Entities
People
- Agnieszka Stadnik
- Alan T. Tang
- Amy Akers
- Anukriti Sharma
- Atif Zafar
- Ceylan Tanes
- Cornelia Lee
- Dongdong Zhang
- Helen Kim
- Issam Awad
- Jack A. Gilbert
- Janne Koskimäki
- Julián Carrión-Penagos
- Kimberly L Yan
- Kyle Bittinger
- Le Shen
- Leslie Morrison
- Mark L. Kahn
- Myranda Robinson
- Patricia Mericko
- Robert Shenkar
- Romuald Girard
- Sean P Polster
- Seán B Lyne
- Sharbel G. Romanos
- Ying Cao
Organizations
- National Institutes of Health
- United States Department of Defense
- United States Department of Health and Human Services