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Review
. 2025 May 28;8(2):pbaf010.
doi: 10.1093/pcmedi/pbaf010. eCollection 2025 Jun.

The gut virome in association with the bacteriome in gastrointestinal diseases and beyond: roles, mechanisms, and clinical applications

Zhiyang Feng  1   2   3 , Elke Burgermeister  4 , Anna Philips  5 , Tao Zuo  1   2   3 , Weijie Wen  1   2   3
Affiliations
Review

The gut virome in association with the bacteriome in gastrointestinal diseases and beyond: roles, mechanisms, and clinical applications

Zhiyang Feng et al. Precis Clin Med. .

Abstract

The gut virome, an essential component of the intestinal microbiome, constitutes ∼0.1% of the total microbial biomass but contains a far greater number of particles than bacteria, with phages making up 90%-95% of this virome. This review systematically examines the developmental patterns of the gut virome, focusing on factors influencing its composition, including diet, environment, host genetics, and immunity. Additionally, it explores the gut virome's associations with various diseases, its interactions with gut bacteria and the immune system, and its emerging clinical applications.

Keywords: colorectal cancer; dietary intervention; fecal microbiota transplantation; gut virome; inflammatory bowel disease; probiotics.

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Conflict of interest statement

None declared. In addition, as an Editorial Board Member of Precision Clinical Medicine, the corresponding author Tao Zuo was blinded from reviewing and making decision on this manuscript.

Figures

Graphical Abstract
Graphical Abstract
Clinical applications of the gut virome in disease therapeutics.
Figure 1.
Figure 1.
Composition of the human gut virome.
Figure 2.
Figure 2.
Mechanisms of interaction between the gut virome and bacteriome. Created in BioRender. Zuo, T. (2025) https://BioRender.com/jasye5j. (A) Bacteriophage life cycles. Phages replicate through three cycles: lytic (host lysis), lysogenic (genome integration), and budding (non-lethal release). (B) Bacterial defense vs. phage countermeasures. Bacteria combat phage infection using systems like CRISPR-Cas, which recognizes and cleaves phage DNA. In response, phages promote the generation of inhibitory proteins and genetic mutations to evade detection, driving a constant evolutionary arms race. (C) Effects of phages on bacterial functions. Phages regulate metabolism, biofilm formation, and virulence. Some phages transfer genes that enhance adherence and invasion to shape bacterial behavior and host interactions.
Figure 3.
Figure 3.
Mechanisms of interaction between the gut virome and mammalian host immunity. Phages within the intestinal mucosa act as a frontline defense, forming a physical barrier while modulating T/B cell activity and macrophage function in a dose-dependent manner. Meanwhile, eukaryotic viruses contribute to immune homeostasis through TLR and RIG-I signaling pathways. However, external disturbances such as infections or antibiotic exposure can disrupt these pathways, reprogramming the immune response from protective to pathological. This shift triggers TLR9-mediated overactivation of Th17 cell responses, resulting in excessive IL-17 production and subsequent mucosal damage. Additionally, phage-induced microbial dysbiosis exacerbates immune imbalance, generating a self-perpetuating cycle that contributes to inflammatory diseases such as IBD. Created in BioRender. Zuo, T. (2025) https://BioRender.com/kexdnt4.
Figure 4.
Figure 4.
Clinical applications of the gut virome in disease therapeutics. Created in BioRender. Zuo, T. (2025) https://BioRender.com/c0hlynx.
See this image and copyright information in PMC

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