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.

Evidence map14 cited passagesInspect provenance +
01
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.

02
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,.

03
Parkinson's Disease

Bacteriophages targeting lactococcus (lytic phages) are enriched in PD patients.

04
Parkinson's Disease

Phage-mediated killing of commensal bacteria may precede and precipitate the bacterial dysbiosis observed in PD.

05
Parkinson's Disease

Combined bacteriophage and bacterial toxin exposure in the gut may contribute to neurodegeneration through the gut brain axis.

06
Parkinson's Disease

Brain virome dysbiosis detected in PD and MSA patients.

07
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. This positions the virome as a potential upstream trigger, not downstream consequence, of dysb

08
Autism Spectrum Disorder

Gut phageome alterations detected in ASD, with disease-specific viral community structures distinguishing ASD children from healthy controls,.

09
PCOS

Phage-Lactobacillus coevolution supports vaginal eubiosis in healthy women; disruption of this phage-bacteria balance is observed in PCOS.

10
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.

11
Long COVID

Reduced phage diversity in long COVID limits natural pathobiont predation, potentially contributing to persistent proteobacteria enrichment and bacterial translocation.

12
Phage Therapy

Safety: Systematic review confirms favorable safety profile with few serious adverse events.

13
Phage Therapy

Cardiometabolic applications: Phage therapy explored for targeting proteobacteria pathobionts in metabolic syndrome.

14
Virome-Bacteriome-Metabolite Interactions

Virome-bacteriome-metabolite interaction networks are fundamentally reorganized in disease

Contents1. Composition2. Virome in Disease3. Phage Therapy4. Virome-Bacteriome-Metabolite Interactions5. Open Questions6. Cross-References

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.[1]Alterations in colorectal cancer virome and its persistence after surgerySi Xian Ho, Jia-Hao Law, Chin-Wen Png et al. · 2024Open reference 1

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.[2]Metagenome-Based Characterization of the Gut Virome in Patients with SchizophreniaRen Y, Zhang P, Yu H et al. · 2025Open reference 2[3]Tao 2025 — Alterations in Fecal Bacteriome Virome Interplay and Microbiota-Derived Dysfunction in Patients with SchizophreniaShiwan Tao, Yulu Wu, Liling Xiao et al. · 2025Open reference 3

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.[4]Tetz 2018 -- Bacteriophage and Gut Dysbiosis in Parkinson's DiseaseGeorge Tetz, Stuart M Brown, Yuhan Hao et al. · 2018Open reference 4 Phage-mediated killing of commensal bacteria may precede and precipitate the bacterial dysbiosis observed in PD.[5]Tetz 2021 -- Gut Virome Alterations in Parkinson's DiseaseGeorge Tetz, Victor Tetz · 2021Open reference 5

Combined bacteriophage and bacterial toxin exposure in the gut may contribute to neurodegeneration through the Gut-Brain Axis.[6]Tetz 2025 -- The Impact of Combined Bacteriophage and Toxin Exposure on Gut Viability in Parkinson's Disease ModelsGeorge Tetz, Victor Tetz · 2025Open reference 6

Brain virome dysbiosis detected in PD and MSA patients.[7]Brain virome dysbiosis in Parkinson's disease and multiple system atrophyMahin Ghorbani, Giorgio Gabarrini, Zamaneh Hajikhezri · 2025Open reference 7

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 (Pseudomonadota) bloom that characterizes NEC.[8]Kaelin 2022 — Gut Virome Signatures Preceding NECKaelin EA, Rodriguez C, Hall-Moore C et al. · 2022Open reference 8

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.[9]Shahin 2023 — Metagenomics Revealed a Correlation of Gut Phageome with Autism Spectrum DisorderKhashayar Shahin, Abbas Soleimani-Delfan, Zihan He et al. · 2023Open reference 9[10]Yuan 2025 -- Comparison of Gut Viral Communities Between Autism Spectrum Disorder and Healthy ChildrenMinli Yuan, Qiuxia Wang, Yan Lu et al. · 2025Open reference 10

PCOS#

Phage-Lactobacillus coevolution supports vaginal eubiosis in healthy women; disruption of this phage-bacteria balance is observed in PCOS.[11]Metagenomic-based characterization of the gut virome in patients with polycystic ovary syndromeHuang L, Wu X, Guo S et al. · 2022Open reference 11

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.[12]Distinct gut virome profiles are associated with response to anti-PD-1 therapy in non-small cell lung cancerZhuo Liu, Meihong Liu, Huixiang Chen et al. · 2026Open reference 12

Long COVID#

Reduced phage diversity in long COVID limits natural pathobiont predation, potentially contributing to persistent Proteobacteria (Pseudomonadota) enrichment and bacterial translocation.[13]Lu et al. 2021 — Alterations in the Composition of Intestinal DNA Virome in Patients With COVID-19Zhen-Hua Lu, Hao-Wei Zhou, Wei-Kang Wu et al. · 2021Open reference 13

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.[14]Safety and efficacy of phage therapy in difficult-to-treat infections: a systematic reviewSaartje Uyttebroek, Baisong Chen, Jolien Onsea et al. · 2022Open reference 14 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 (Pseudomonadota) pathobionts in metabolic syndrome.[15]Opportunities and challenges in phage therapy for cardiometabolic diseasesKoen Wortelboer, Hilde Herrema · 2024Open reference 15 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.[3]Tao 2025 — Alterations in Fecal Bacteriome Virome Interplay and Microbiota-Derived Dysfunction in Patients with SchizophreniaShiwan Tao, Yulu Wu, Liling Xiao et al. · 2025Open reference 3

Open Questions#

Unresolved questions identified by the current evidence record.

01Metal effects on phages: Do Heavy Metals directly affect phage stability or host range?

Prophage induction under metal stress could reshape the virome.

02Phage-metal resistance transfer: Phages are major vectors for horizontal gene transfer—do they spread metal resistance genes alongside ARGs?

The current WikiBiome record identifies this as an unresolved evidence gap.

03Temporal dynamics: The NEC virome convergence finding suggests phage shifts precede bacterial dysbiosis. Is this pattern general across diseases?

The current WikiBiome record identifies this as an unresolved evidence gap.

04Therapeutic targeting: Can phage cocktails be designed to selectively remove metal-tolerant pathobionts while sparing iron (Fe)-S-dependent commensals?

The current WikiBiome record identifies this as an unresolved evidence gap.

Cross-References#

Generated evidence record

References 19

Numbered by first appearance in the article, then reconciled with its declared source list.

  1. 1

    Si Xian Ho, Jia-Hao Law, Chin-Wen Png et al. (2024). Alterations in colorectal cancer virome and its persistence after surgery. Scientific Reports.

  2. 2

    Ren Y, Zhang P, Yu H et al. (2025). Metagenome-Based Characterization of the Gut Virome in Patients with Schizophrenia. Journal of Translational Medicine.

  3. 3

    Shiwan Tao, Yulu Wu, Liling Xiao et al. (2025). Tao 2025 — Alterations in Fecal Bacteriome Virome Interplay and Microbiota-Derived Dysfunction in Patients with Schizophrenia. Translational Psychiatry.

  4. 4

    George Tetz, Stuart M Brown, Yuhan Hao et al. (2018). Tetz 2018 -- Bacteriophage and Gut Dysbiosis in Parkinson's Disease. Scientific Reports.

  5. 5

    George Tetz, Victor Tetz (2021). Tetz 2021 -- Gut Virome Alterations in Parkinson's Disease. Communications Biology.

  6. 6

    George Tetz, Victor Tetz (2025). Tetz 2025 -- The Impact of Combined Bacteriophage and Toxin Exposure on Gut Viability in Parkinson's Disease Models. Scientific Reports.

  7. 7

    Mahin Ghorbani, Giorgio Gabarrini, Zamaneh Hajikhezri (2025). Brain virome dysbiosis in Parkinson's disease and multiple system atrophy. Frontiers in Microbiology.

  8. 8

    Kaelin EA, Rodriguez C, Hall-Moore C et al. (2022). Kaelin 2022 — Gut Virome Signatures Preceding NEC. Nature Microbiology.

  9. 9

    Khashayar Shahin, Abbas Soleimani-Delfan, Zihan He et al. (2023). Shahin 2023 — Metagenomics Revealed a Correlation of Gut Phageome with Autism Spectrum Disorder. Gut Pathogens.

  10. 10

    Minli Yuan, Qiuxia Wang, Yan Lu et al. (2025). Yuan 2025 -- Comparison of Gut Viral Communities Between Autism Spectrum Disorder and Healthy Children. Frontiers in Cellular and Infection Microbiology.

  11. 11

    Huang L, Wu X, Guo S et al. (2022). Metagenomic-based characterization of the gut virome in patients with polycystic ovary syndrome. Frontiers in Microbiology.

  12. 12

    Zhuo Liu, Meihong Liu, Huixiang Chen et al. (2026). Distinct gut virome profiles are associated with response to anti-PD-1 therapy in non-small cell lung cancer. Journal of Translational Medicine.

  13. 13

    Zhen-Hua Lu, Hao-Wei Zhou, Wei-Kang Wu et al. (2021). Lu et al. 2021 — Alterations in the Composition of Intestinal DNA Virome in Patients With COVID-19. Frontiers in Cellular and Infection Microbiology.

  14. 14

    Saartje Uyttebroek, Baisong Chen, Jolien Onsea et al. (2022). Safety and efficacy of phage therapy in difficult-to-treat infections: a systematic review. The Lancet Infectious Diseases.

  15. 15

    Koen Wortelboer, Hilde Herrema (2024). Opportunities and challenges in phage therapy for cardiometabolic diseases. Trends in Endocrinology and Metabolism.

  16. 16

    Patrick A. de Jonge, Koen Wortelboer, Torsten P. M. Scheithauer et al. (2022). Gut virome profiling identifies a widespread bacteriophage family associated with metabolic syndrome. Nature Communications.

  17. 17

    Kosuke Fujimoto, Daichi Miyaoka, Satoshi Uematsu (2022). Characterization of the Human Gut Virome in Metabolic and Autoimmune Diseases. Inflammation and Regeneration.

  18. 18

    George Tetz, Victor Tetz (2022). Tetz 2022 -- The Effects of Gut Dysbiosis via Bacteriophages and Its Role in Parkinson's Disease. Pathogens.

  19. 19

    George Tetz, Victor Tetz (2024). Tetz 2024 -- The Impact of Bacteriophage on the Aging Brain and Inflammatory Response: Relevance to Parkinson's Disease. Scientific Reports.

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