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  • Review Article
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Gut virome dynamics: from commensal to critical player in health and disease

Nature Reviews Gastroenterology & Hepatology volume 23, pages 126–144 (2026)Cite this article

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Abstract

The gut virome is a complex ecosystem characterized by the interplay of diverse viral entities, predominantly bacteriophages and eukaryotic viruses. The gut virome has a critical role in human health by shaping microbial community profiles, modulating host immunity and influencing metabolic processes. Different viral metagenomics approaches have revealed the remarkable diversity of the gut virome, showing individual-specific patterns that evolve over time and adapt dynamically to environmental factors. Perturbations in this community are increasingly associated with chronic immune and inflammatory conditions, metabolic disorders and neurological conditions, highlighting its potential as a diagnostic biomarker and therapeutic target. The early-life gut virome is particularly influential in establishing lifelong health trajectories through its interactions with diet, immune pathways and others, thereby contributing to inflammatory and metabolic regulation. This Review synthesizes current knowledge of gut virome composition, dynamics and functional relevance, critically evaluating evidence distinguishing causal from correlative roles in disease pathogenesis. The interactions of the virome with other microbiome components and host immunity are examined, and emerging translational applications, including phage therapy and biomarker development, are discussed. Integrating these insights while acknowledging methodological challenges provides a comprehensive framework for understanding the complex roles of the gut virome in health and disease.

Key points

  • The gut virome, primarily composed of bacteriophages and eukaryotic viruses, substantially influences gut microbiota dynamics, immune responses and metabolic health.

  • Next-generation methods and state-of-the-art bioinformatics tools have identified numerous newly characterized viral entities with potential associations to health and disease.

  • Individual virome composition exhibits high variability, shaped by early-life exposures and sustained environmental interactions, and alterations in gut virome composition correlate with diverse diseases, including inflammatory bowel diseases, metabolic disorders, neurological conditions and cancer.

  • Prophage induction, driven by environmental factors, profoundly influences microbial community structure and host immune responses.

  • Therapeutic strategies such as phage therapy and faecal virome transplantation represent targeted approaches to restore gut microbial equilibrium.

  • Addressing methodological biases and ‘viral dark matter’ is critical for elucidating the role of the gut virome in health and disease, as disease states are commonly linked to high prevalence uncharacterized viral entities.

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Fig. 1: Molecular approaches to study the human gut virome.
Fig. 2: Gut virome dynamics: protective roles, lytic and lysogenic cycles, and immune interactions.

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Acknowledgements

Research is funded by grants from the National Institutes of Health, including RC2DK116713 awarded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to S.A.H., R01AI173360 awarded by the National Institute of Allergy and Infectious Diseases (NIAID) to M.T.B. and S.A.H., U01AT012998 awarded by the National Center for Complementary and Integrative Health (NCCIH) to M.T.B. and S.A.H., and U24HL175772 awarded by the National Heart, Lung, and Blood Institute (NHLBI).

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Authors and Affiliations

  1. Edison Family Center for Genome Sciences & Systems Biology, Washington University School of Medicine, St. Louis, MO, USA

    Luis A. Chica Cardenas, Megan T. Baldridge & Scott A. Handley

  2. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA

    Luis A. Chica Cardenas & Scott A. Handley

  3. Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA

    Luis A. Chica Cardenas & Megan T. Baldridge

  4. Division of Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital for Children, Harvard Medical School, Boston, MA, USA

    Maureen M. Leonard

  5. Mucosal Immunology and Biology Research Center, Massachusetts General Hospital for Children, Harvard Medical School, Boston, MA, USA

    Maureen M. Leonard

  6. Celiac Research Program, Harvard Medical School, Boston, MA, USA

    Maureen M. Leonard

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Competing interests

M.M.L. is a consultant to EllaOla, Takeda Pharmaceuticals and Anokion, has received research support from Takeda and Moderna (to institution), and has acted as a study investigator for Merck, Regeneron, Pfizer and Takeda Pharmaceuticals (to institution). The other authors declare no competing interests.

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Nature Reviews Gastroenterology & Hepatology thanks Tao Zuo, who co-reviewed with Ziyu Huang; and Junhua Li for their contribution to the peer review of this work.

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Glossary

Auxiliary metabolic genes

Genes carried by viruses that encode metabolic functions and can supplement or modify host cell metabolism during infection.

CrAssphages

The most abundant bacteriophage discovered in human gut metagenomes through cross-assembly analysis.

Dysbiosis

An imbalance in microbial community composition and function characterized by altered abundance of key taxa or disrupted ecological interactions with potential effects on health.

Lysogenic conversion

The process by which prophage genes alter the phenotype of the bacterial host, potentially conferring new capabilities such as toxin production or antibiotic resistance.

Lysogeny

The viral life cycle state where phage DNA integrates into the bacterial chromosome and replicates passively with the bacterial host without causing immediate lysis.

Prophage induction

The process by which integrated viral DNA (prophage) exits the bacterial chromosome and initiates viral replication, leading to bacterial cell lysis.

Temperate phages

Bacteriophages capable of both lytic (immediate bacterial host lysis) and lysogenic (chromosomal integration) life cycles.

Viral dark matter

The large fraction of viral sequences in metagenomes that cannot be taxonomically classified due to lack of similarity to known viral genomes.

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Chica Cardenas, L.A., Leonard, M.M., Baldridge, M.T. et al. Gut virome dynamics: from commensal to critical player in health and disease. Nat Rev Gastroenterol Hepatol 23, 126–144 (2026). https://doi.org/10.1038/s41575-025-01134-z

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