The human gastrointestinal tract is home to an extraordinarily diverse and dynamic community of viruses, collectively referred to as the gut virome. This viral component of the microbiome has emerged as a critical, yet comparatively understudied, player in intestinal homeostasis, microbial ecology, and overall human health. Historically, research on the gut microbiome has focused predominantly on bacteria, driven by their abundance and well-established roles in digestion, immunity, and disease. However, accumulating evidence indicates that viruses (particularly bacteriophages) are far more than passive inhabitants. They actively shape microbial diversity, mediate horizontal gene transfer, and influence host–microbe interactions through mechanisms that remain only partially understood (Ogilvie & Jones, 2015; Shkoporov et al., 2019)
Advances in metagenomics have enabled high-resolution profiling of the virome, revealing its remarkable diversity, individuality, and potential involvement in both health and disease (Gregory et al., 2020; Zuo et al., 2020).
Composition of the Gut Virome
The gut virome primarily consists of bacteriophages, eukaryotic viruses, and, to a lesser extent, archaeal viruses. Phages dominate numerically, often representing more than 90% of viral particles in fecal samples (Shkoporov et al., 2019). These phages mainly infect bacteria within the Bacillota, Bacteroidota, and Actinomycetota phyla, influencing bacterial population dynamics and community structure through predation and horizontal gene transfer (Minot et al., 2013). Eukaryotic viruses, such as Anelloviridae and Adenoviridae, are less abundant but may directly interact with the host immune system (Cao et al., 2022).
Recent large-scale viromic initiatives have substantially expanded our understanding of viral diversity in the human gut. The Gut Virome Database (GVD), for example, catalogued over 33,000 unique viral populations, uncovering extensive uncharacterized diversity and revealing age-dependent shifts in virome composition (Gregory et al., 2020). Building on this foundation, Galperina et al. (2025) developed the Aggregated Gut Viral Catalogue (AVrC)—a comprehensive, modular resource comprising 1,018,941 dereplicated viral sequences, including 449,859 species-level viral operational taxonomic units (vOTUs). Through advanced computational inference, the AVrC provides detailed annotations for each representative sequence, encompassing sequence quality, viral taxonomy, predicted lifestyle, and putative host associations.
The gut virome exhibits high interindividual variability but also long-term intraindividual stability. Shkoporov et al., (2019) demonstrated that each person harbors a unique and stable viral community, suggesting a personalized viral “fingerprint.” Despite this stability, longitudinal analyses have revealed dynamic processes such as phage–bacteria coevolution and rapid viral turnover, particularly among lytic phages (Minot et al., 2013).
Virome composition is also shaped by host factors, including age, diet, geography, and lifestyle. Zuo et al. (2020) reported distinct DNA virome signatures associated with different populations, reflecting both genetic and environmental influences. Notably, infant viromes are enriched in temperate phages and expand in complexity with age, paralleling bacterial microbiome maturation (Gregory et al., 2020).
Functional Roles
Phages act as critical regulators of microbial homeostasis, maintaining bacterial diversity and preventing dominance of specific taxa through predator–prey dynamics (Ogilvie & Jones, 2015). They contribute to horizontal gene transfer, disseminating genes involved in metabolism, virulence, and antibiotic resistance (Minot et al., 2013).
In health, the gut virome participates in immune modulation by shaping bacterial antigen exposure and influencing mucosal immunity (Cao et al., 2022). In contrast, virome dysbiosis—characterized by altered viral richness or expansion of specific phages—has been implicated in diseases such as inflammatory bowel disease (IBD), Clostridioides difficile infection, and metabolic disorders (Cao et al., 2022; Norman et al., 2015). For instance, IBD patients show elevated levels of Caudovirales phages and reduced viral diversity, suggesting a disruption in phage–bacteria equilibrium (Norman et al., 2015).
The Gut Virome in Therapeutic Contexts
Therapeutically, the virome represents both a target and a tool. Phage therapy is gaining renewed attention as an alternative to antibiotics, offering specificity in targeting pathogenic bacteria while preserving commensals (Cao et al., 2022). Moreover, fecal virome transplantation (FVT), the transfer of purified viral fractions from healthy donors, has shown potential in modulating bacterial communities and restoring gut homeostasis, particularly in recurrent C. difficile infection (Zuo et al., 2020).
Understanding virome dynamics may also enhance the efficacy of fecal microbiota transplantation (FMT), as evidence suggests that successful bacterial engraftment is accompanied by concurrent transfer of viral communities (Cao et al., 2022).
Future Directions
The study of the virome is constrained by methodological limitations. Unlike bacterial genomes, viral genomes lack universal marker genes, complicating taxonomic classification (Ogilvie & Jones, 2015). Metagenomic assembly and annotation remain challenging due to the large proportion of viral “dark matter” (sequences with no known homologs) (Gregory et al., 2020).
Emerging techniques, such as virome-enriched metagenomics, long-read sequencing, and CRISPR spacer analysis, are improving resolution and enabling the discovery of novel viral lineages (Gregory et al., 2020). Integration of multi-omics approaches, including metatranscriptomics and metabolomics, is expected to elucidate functional viral–host interactions in greater detail (Cao et al., 2022).
References
Cao, Z., Sugimura, N., Burgermeister, E., Ebert, M. P., Zuo, T., & Lan, P. (2022). The gut virome: A new microbiome component in health and disease. EBioMedicine, 81, 104113. https://doi.org/10.1016/j.ebiom.2022.104113
Galperina, A., Lugli, G. A., Milani, C., De Vos, W. M., Ventura, M., Salonen, A., Hurwitz, B., & Ponsero, A. J. (2025). The Aggregated Gut Viral Catalogue (AVrC): A unified resource for exploring the viral diversity of the human gut. PLoS computational biology, 21(5), e1012268. https://doi.org/10.1371/journal.pcbi.1012268
Gregory, A. C., Zablocki, O., Zayed, A. A., Howell, A., Bolduc, B., & Sullivan, M. B. (2020). The Gut Virome Database Reveals Age-Dependent Patterns of Virome Diversity in the Human Gut. Cell host & microbe, 28(5), 724–740.e8. https://doi.org/10.1016/j.chom.2020.08.003
Minot, S., Bryson, A., Chehoud, C., Wu, G. D., Lewis, J. D., & Bushman, F. D. (2013). Rapid evolution of the human gut virome. Proceedings of the National Academy of Sciences of the United States of America, 110(30), 12450–12455. https://doi.org/10.1073/pnas.1300833110
Norman, J. M., Handley, S. A., Baldridge, M. T., Droit, L., Liu, C. Y., Keller, B. C., Kambal, A., Monaco, C. L., Zhao, G., Fleshner, P., Stappenbeck, T. S., McGovern, D. P., Keshavarzian, A., Mutlu, E. A., Sauk, J., Gevers, D., Xavier, R. J., Wang, D., Parkes, M., & Virgin, H. W. (2015). Disease-specific alterations in the enteric virome in inflammatory bowel disease. Cell, 160(3), 447–460. https://doi.org/10.1016/j.cell.2015.01.002
Ogilvie, L. A., & Jones, B. V. (2015). The human gut virome: a multifaceted majority. Frontiers in microbiology, 6, 918. https://doi.org/10.3389/fmicb.2015.00918
Shkoporov, A. N., Clooney, A. G., Sutton, T. D. S., Ryan, F. J., Daly, K. M., Nolan, J. A., McDonnell, S. A., Khokhlova, E. V., Draper, L. A., Forde, A., Guerin, E., Velayudhan, V., Ross, R. P., & Hill, C. (2019). The Human Gut Virome Is Highly Diverse, Stable, and Individual Specific. Cell host & microbe, 26(4), 527–541.e5. https://doi.org/10.1016/j.chom.2019.09.009
Zuo, T., Sun, Y., Wan, Y., Yeoh, Y. K., Zhang, F., Cheung, C. P., Chen, N., Luo, J., Wang, W., Sung, J. J. Y., Chan, P. K. S., Wang, K., Chan, F. K. L., Miao, Y., & Ng, S. C. (2020). Human-Gut-DNA Virome Variations across Geography, Ethnicity, and Urbanization. Cell host & microbe, 28(5), 741–751.e4. https://doi.org/10.1016/j.chom.2020.08.005