Scientists uncover how the smallest phage from human gut interacts with its host

Phages are important components of the human gut microbiome. Through interactions with bacteria—such as infecting and lysing their hosts and releasing bacterial cellular contents—they play a crucial role in shaping the gut microbial community and, in turn, influence human health.

The Microviridae family, is characterized by a small genome and a tiny capsid. Although members of this family are prevalent in the human gut, as revealed by metagenomic analyses, they have never been isolated directly from the human gut. In a study published in the KeAi journal Engineering Microbiology, a research group from China isolated and characterized a Microviridae phage (hereafter, φHBP1) using Bacteroides fragilis as host, gut commensal bacterium belonging to the phylum Bacteroidota.

"Many bacteria can rapidly modify their genetic materials to alter gene expression through, for example, inversion of promoter regions," explains the study's corresponding author Wenyuan Han, a professor at  National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University. "This strategy, called phase variation, can increase bacterial phenotypic diversity and adaptability to fast varying environments, including phage invasion."

As with other bacteria, B. fragilis exploits phase variation to develop resistance to φHBP1. The phase variation loci include restriction-modification systems and susC/susD gene clusters. The former might alter epigenetic modifications, while the latter might lead to diverse changes in bacterial surface structures. "These alteration may affect the phage absorbance, thus protecting cells from phage invasion," adds Han.

Interestingly,  φHBP1 is not totally helpless when challenged by the bacterial phase variation strategy. It can evolves to gain infectivity by acquiring mutations within the viral capsid protein and the pilot protein. "These mutations may enable φHBP1 to infect cells with a distinct phase variation genotype and altered surface structure," says Han.

The team's findings reflect how bacteria and phages co-exist in a constanting "arms-race" through generating genetic heterogeneity, and suggest that phage evolution serves a powerful strategy to produce phage variants that can be used in phage therapy to treat pathogenic bacterial infections.

"Indeed, we demonstrate that a mixture of the evolved φHBP1 variants can reduce the emergence rate of phage-resistant B. fragilis." Han says. "We hope that further study of bacteria-phage interaction will eventually promote the clinical applications of phages to treat gut bacterial infections."

Contact author details: 

Wenyuan Han, College of Life Science and Technology, National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China. hanwenyuan@mail.hzau.edu.cn 

Funder: 

This work was supported by the National Key Research and Development program of China 2022YFA0912200, Fundamental Research Funds for Central Universities 2662024SKPY003, Foundation of Hubei Hongshan Laboratory 2021hszd022, Hubei Special Project for Science Development 2024CSA060.

Conflict of interest: 

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

See the article: Huang, P., et al., Phase variation in Bacteroides fragilis governs susceptibility to a microvirus and drives its evolution, Engineering Microbiology, Volume 6, Issue 1, 2026, 100252, https://doi.org/10.1016/j.engmic.2025.100252