The human gut is home to trillions of microbes, yet scientific understanding has largely focused on bacteria, leaving the virome—the community of viruses—relatively uncharted. Bacteriophages, which infect bacteria, are the dominant members, outnumbering their bacterial hosts and subtly guiding microbial composition through predation and gene exchange. Eukaryotic viruses, meanwhile, influence immune responses and may trigger inflammation when balance is disrupted. Factors like diet, hygiene, and genetics shape these viral populations, but their precise roles remain elusive. Due to these challenges, more attention is now being directed toward understanding how the virome contributes to both microbial stability and disease onset. Because of these knowledge gaps, deeper investigation into the gut virome's role in health and disease is urgently needed.
In a sweeping review (DOI: 10.1093/pcmedi/pbaf010) published on May 28, 2025, in Precision Clinical Medicine, researchers from Sun Yat-sen University, University of Heidelberg, and the Polish Academy of Sciences dive deep into the complex world of the gut virome. Drawing on emerging mechanistic and clinical data, the study explores how viral communities—particularly bacteriophages—regulate gut ecology, interact with host immunity, and influence the onset and progression of major gastrointestinal diseases. By connecting the dots between virome dynamics and therapeutic outcomes, the authors propose a new framework for treating gut disorders through viral modulation.
The study tracks the gut virome across life stages, revealing a constantly shifting viral landscape shaped by age, diet, geography, and immune function. Phages dominate this ecosystem, orchestrating microbial shifts through cycles of infection that either kill bacteria or integrate into their genomes. These interactions shape bacterial metabolism, immune activation, and even the potential for disease. In disorders like inflammatory bowel disease (IBD), a rise in pro-inflammatory phages and loss of protective ones amplify inflammation through immune triggers like Toll-like receptor 9 (TLR9). In colorectal cancer, phages may fuel tumor growth by stabilizing biofilms and transferring cancer-promoting genes. Meanwhile, eukaryotic viruses such as HPV and EBV are increasingly found in tumor tissues, hinting at a more direct role in disease progression. Perhaps most striking, therapies that target the virome—such as fecal virome transplantation or dietary interventions—are showing promise in restoring gut balance and reducing disease severity. The review also emphasizes that viral changes don't always follow bacterial shifts—sometimes, they lead them—positioning the virome as both a driver and a mirror of gut health.
"The virome is no longer just a mysterious backdrop to the microbiome—it's an active, dynamic force," said Prof. Tao Zuo, corresponding author of the study. "We now see that viruses, especially bacteriophages, are capable of shaping gut ecosystems in ways we're only beginning to understand. They could be the missing link in why some patients respond to therapies while others don't. As our ability to target and engineer these viral populations grows, so too does the potential to revolutionize how we approach gut-related diseases."
Harnessing the gut virome opens up new frontiers in precision medicine. Phage therapy offers the ability to selectively eliminate harmful bacteria without disturbing beneficial microbes, while fecal virome transplantation could provide more targeted results than conventional FMT. Dietary strategies—from fiber-rich plans to amino acid-restricted regimens—can also reshape the viral landscape to restore intestinal balance. Virome-based biomarkers may offer early, noninvasive disease detection and help guide personalized treatment strategies. As viral profiling and synthetic phage engineering advance, clinicians may soon gain new tools to rebalance gut ecosystems and intervene in inflammatory and cancerous processes before they spiral out of control.
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References
DOI
10.1093/pcmedi/pbaf010
Original Source URL
https://doi.org/10.1093/pcmedi/pbaf010
Funding information
This work was supported by the National Natural Science Foundation of China (Grants No. 82172323, 32100134, 823B2010), Guangdong Provincial Natural Science Foundation (Grant No. 2024A1515010533), Guangzhou Key R&D program (Grant No. 202206010014), and a seed fund from the Sixth Affiliated Hospital of Sun Yat-sen University and Sun Yat-sen University (Grant No. 2022JBGS03).
About Precision Clinical Medicine
Precision Clinical Medicine (PCM) commits itself to the combination of precision medical research and clinical application. PCM is an international, peer-reviewed, open-access journal that publishes original research articles, reviews, clinical trials, methodologies, perspectives in the field of precision medicine in a timely manner. By doing so, the journal aims to provide new theories, methods, and evidence for disease diagnosis, treatment, prevention and prognosis, so as to establish a communication platform for clinicians and researchers that will impact practice of medicine. The journal covers all aspects of precision medicine, which uses novel means of diagnosis, treatment and prevention tailored to the needs of a patient or a sub-group of patients based on the specific genetic, phenotypic, or psychosocial characteristics. Clinical conditions include cancer, infectious disease, inherited diseases, complex diseases, rare diseases, etc. The journal is now indexed in ESCI, Scopus, PubMed Central, etc., with an impact factor of 5.0 (JCR2024, Q1).