The Virome: Clinical Implications of Gut Viruses

July 12, 2022 by Flore Clinical Editorial

The gut virome — comprising primarily bacteriophages (viruses that infect bacteria), eukaryotic viruses, and endogenous retroviruses — is the most abundant and poorly characterized component of the gut microbiome. An estimated 10¹² phage particles reside per gram of stool, outnumbering bacteria 10:1. The virome is not a bystander but an active regulator of bacterial community composition and by extension, host physiology.

Bacteriophages as Microbiome Regulators

Phages shape bacterial community composition through predator-prey dynamics (kill-the-winner hypothesis), horizontal gene transfer, and lysogeny — where phage DNA integrates into the bacterial chromosome and can provide new metabolic capabilities or virulence factors. Phage populations are highly individual, explaining in part why two people with the same dietary intake have different microbiome compositions. Dysbiosis in the virome — dysvirome — precedes bacterial dysbiosis in several disease states.

Clinical Associations of the Virome

Virome alterations are documented in: IBD (expansion of Caudovirales phages targeting commensal bacteria), type 1 diabetes (enterovirus-driven pancreatic beta cell dysfunction), HIV/AIDS (dramatic virome expansion with altered phage-bacteria ratios), colorectal cancer, and major depression. Germ-free mouse colonized with human IBD virome develops intestinal inflammation — establishing causal virome contributions to IBD.

Phage Therapy: The Clinical Horizon

Bacteriophage therapy for antibiotic-resistant infections is undergoing clinical trial evaluation. Phages targeting MRSA, Pseudomonas aeruginosa, and multi-drug-resistant Klebsiella have been used in compassionate cases with dramatic outcomes reported in case series. The challenge is phage specificity — a therapeutic phage must match the precise bacterial strain targeted — requiring phage banking or rapid in vitro phage selection. This is not currently standard of care but represents a compelling future therapeutic direction.

Related: Microbiome Fundamentals · Antibiotic Stewardship

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