Overview
The virome is the collection of all viruses inhabiting a given ecosystem — in the gut, this means primarily bacteriophages (phages), which constitute ~90% of the intestinal virome. While microbiome research has historically focused on bacteria, mounting evidence shows the virome is not a passive bystander but an active ecological force: phages shape bacterial community composition through selective predation, horizontal gene transfer, and modulation of bacterial fitness. In several conditions, virome-based classifiers outperform bacterial signatures for disease prediction.
The gut virome is the "dark matter" of the microbiome — poorly characterized relative to the bacteriome, but increasingly recognized as a driver of dysbiosis rather than merely a consequence.
Composition
Bacteriophages (~90%)
- Caudovirales (tailed phages): Siphoviridae, Myoviridae, Podoviridae — the dominant order in the healthy gut
- CrAss-like phages: The most abundant and stable phages in the human gut, infecting Bacteroides species
- Temperate phages: Integrated as prophages in bacterial genomes; can be induced by stress (antibiotics, oxidative stress, metal exposure)
Eukaryotic Viruses (~10%)
- Plant-derived viruses (dietary origin)
- Human viruses (enteroviruses, adenoviruses — typically low abundance in healthy individuals)
- Endogenous retroviruses (integrated in the human genome)
Virome in Disease
Colorectal Cancer
The CRC fecal virome shows increased network connectivity — phage-bacteria interaction networks become more complex and interconnected. Virome dysbiosis persists even after surgical resection, suggesting the virome changes are not simply a consequence of tumor presence but may reflect a stable ecological state ho 2024 colorectal cancer virome alterations persistence surgery.
Schizophrenia
124 viral operational taxonomic units (vOTUs) are enriched in schizophrenia (primarily Siphoviridae and Flandersviridae). A virome-based classifier achieved AUC 93.2% — outperforming both bacterial and mycobiome models for disease discrimination ren 2025 gut virome schizophrenia metagenomics, tao 2025 fecal virome bacteriome metabolite interplay schizophrenia.
Parkinson's Disease
The Tetz group has published a series of studies linking gut phages to PD pathogenesis. Key findings:
- Bacteriophages targeting lactococcus (lytic phages) are enriched in PD patients tetz 2018 parkinsons bacteriophage gut dysbiosis.
- Phage-mediated killing of commensal bacteria may precede and precipitate the bacterial dysbiosis observed in PD tetz 2021 gut virome parkinsons bacteriophages.
- Combined bacteriophage and bacterial toxin exposure in the gut may contribute to neurodegeneration through the gut brain axis tetz 2025 combined bacteriophage toxin gut parkinsons.
- Brain virome dysbiosis detected in PD and MSA patients ghorbani 2025 brain virome dysbiosis parkinsons msa.
Necrotizing Enterocolitis
A critical finding: virome convergence occurs ~10 days before NEC onset — phage community composition shifts dramatically before clinical disease appears. Phage-mediated killing of commensal bacteria may precipitate the proteobacteria bloom that characterizes NEC kaelin 2022 gut virome signatures preceding nec. This positions the virome as a potential upstream trigger, not downstream consequence, of dysbiosis.
Autism Spectrum Disorder
Gut phageome alterations detected in ASD, with disease-specific viral community structures distinguishing ASD children from healthy controls shahin 2023 gut phageome asd metagenomics, yuan 2025 gut viral communities asd healthy children.
PCOS
Phage-Lactobacillus coevolution supports vaginal eubiosis in healthy women; disruption of this phage-bacteria balance is observed in PCOS huang 2022 gut virome pcos metagenomic characterization.
Cancer Immunotherapy Response
The gut virome predicts immunotherapy response with AUC 0.768 vs 0.664 for bacteria-only models. Responder-enriched phages target SCFA producers (faecalibacterium prausnitzii, roseburia); non-responder phages target clostridium/bacteroides fragilis liu 2026 gut virome anti pd1 nsclc.
Long COVID
Reduced phage diversity in long COVID limits natural pathobiont predation, potentially contributing to persistent proteobacteria enrichment and bacterial translocation lu 2021 intestinal dna virome covid 19.
Phage Therapy
Phage therapy — using lytic bacteriophages to selectively kill pathogenic bacteria — is experiencing a resurgence as antibiotic resistance escalates:
- Safety: Systematic review confirms favorable safety profile with few serious adverse events uyttebroek 2022 phage therapy safety efficacy systematic review.
- Specificity: Phages are highly specific to their bacterial hosts, theoretically sparing the commensal community (unlike broad-spectrum antibiotics).
- Cardiometabolic applications: Phage therapy explored for targeting proteobacteria pathobionts in metabolic syndrome wortelboer 2024 phage therapy cardiometabolic diseases.
- Pancreatic cancer: Phage-based peptide delivery systems explored for targeting intratumoral bacteria.
Virome-Bacteriome-Metabolite Interactions
The virome does not operate in isolation. In schizophrenia, tripartite analysis revealed:
- Phage abundance correlates with bacterial host abundance (predator-prey dynamics)
- Phage-mediated bacterial lysis releases metabolites that influence host neurotransmitter pathways
- Virome-bacteriome-metabolite interaction networks are fundamentally reorganized in disease tao 2025 fecal virome bacteriome metabolite interplay schizophrenia
Open Questions
- Metal effects on phages: Do heavy metals directly affect phage stability or host range? Prophage induction under metal stress could reshape the virome.
- Phage-metal resistance transfer: Phages are major vectors for horizontal gene transfer — do they spread metal resistance genes alongside ARGs?
- Temporal dynamics: The NEC virome convergence finding suggests phage shifts precede bacterial dysbiosis. Is this pattern general across diseases?
- Therapeutic targeting: Can phage cocktails be designed to selectively remove metal-tolerant pathobionts while sparing Fe-S-dependent commensals?
Cross-References
- gut microbiome — The virome as the overlooked component
- proteobacteria — Phylum whose bloom may be triggered by phage-mediated commensal killing
- dysbiosis — Virome dysbiosis as upstream trigger
- antimicrobial resistance — Phage therapy as alternative to antibiotics
- gut brain axis — Phage-toxin-neurodegeneration pathway
- probiotics — Phage-probiotic coevolution in health
- firmicutes — SCFA producers targeted by responder vs. non-responder phages