The Virome of Cerebrospinal Fluid: Viruses Where We Once Thought There Were None

Abstract

Traditionally, medicine has held that some human body sites are sterile and that the introduction of microbes to these sites results in infections. This paradigm shifted significantly with the discovery of the human microbiome and acceptance of these commensal microbes living across the body. However, the central nervous system (CNS) is still believed by many to be sterile in healthy people. Using culture-independent methods, we examined the virome of cerebrospinal fluid (CSF) from a cohort of mostly healthy human subjects. We identified a community of DNA viruses, most of which were identified as bacteriophages. Compared to other human specimen types, CSF viromes were not ecologically distinct. There was a high alpha diversity cluster that included feces, saliva, and urine, and a low alpha diversity cluster that included CSF, body fluids, plasma, and breast milk. The high diversity cluster included specimens known to have many bacteria, while other specimens traditionally assumed to be sterile formed the low diversity cluster. There was an abundance of viruses shared among CSF, breast milk, plasma, and body fluids, while each generally shared less with urine, feces, and saliva. These shared viruses ranged across different virus families, indicating that similarities between these viromes represent more than just a single shared virus family. By identifying a virome in the CSF of mostly healthy individuals, it is now less likely that any human body site is devoid of microbes, which further highlights the need to decipher the role that viral communities may play in human health.

Diversity of Vaginal Microbiome in Pregnancy: Deciphering the Obscurity

“…Apart from the gut virome, fewer studies have been conducted to study virome in oral cavity, CSF, cervix, respiratory system, skin, blood, conjunctiva, urinary tract, and breast milk. Skin and CSF, in absolute contrast to the gut, has low biomass communities with a predominance of bacteriophages (98,99). The studies on virome in oral cavity have revealed the ubiquitous presence of certain genotypes, along with the personalized, persistent virome associated with some of these and is thought to be hormonal-driven.…”

Bacteriophage K1F targets Escherichia coli K1 in cerebral endothelial cells and influences the barrier function

“…Virulent bacteriophages (or phages) propagate within a suitable host at the site of infection, ultimately lysing that host and repeating the cycle, allowing for the potential of single-dose administration to eradicate a large number of bacterial cells 9 . Phage therapy was reported to successfully treat meningitis caused by multiple pathogens as early as at the turn of the 21 st century 10,11 manifesting the ability of phages to cross physiological barriers, including the BBB 12 , whereas many antimicrobials, including vancomycin, beta-lactams and other hydrophilic antibiotics have reduced penetration across the BBB 13 . Studies performed in a rat meningitis model infected with E. coli O25b:H4-ST131, a strain producing extended-spectrum beta-lactamase CTx-M-15, showed 100% and 50% rat survival following administration of phage EC200 PP 7 or 24 h post-infection respectively 14 .…”

Potential Applications of Human Viral Metagenomics and Reference Materials: Considerations for Current and Future Viruses

“…In the case of viromes, however, utilizing Illumina vs. Ion Torrent sequencing may not affect the diversity output. This has been noted for cerebrospinal fluid, where viral alpha-and beta-diversity were not significantly altered by the sequencing platform (6). Additional studies are needed to understand the effect of the sequencing platform on more complex samples (e.g.…”

“…Despite these challenges, viruses are important members of the human microbiome. Viruses are present across the body, at sites, including the gut ( 1 ), the skin ( 2 ), and the oral cavity ( 3 ), and they can inhabit body sites and samples types previously thought to be sterile, including the bladder ( 4 ), blood ( 5 ), and cerebrospinal fluid ( 6 ). Certain viruses can be acquired through birth and continue to be seeded by the maternal bond ( 7 ) and shaped by dietary habits ( 8 ), as well as intimate contact ( 9 ).…”