Bacteriophages of the Human Virome

Bacteriophages are found throughout the human body and may even outnumber eukaryotic viruses, forming an important and dynamic component of the human virome. In the gut, phage densities reach up to 10⁹ particles per gram of fecal matter. They concentrate on mucosal surfaces including the respiratory tract and epithelial barriers, where they bind via capsid proteins to mucin glycoproteins.

On mucosal surfaces, bacteriophages bind to mucin glycoproteins via capsid proteins, concentrating at the epithelial barrier. This interaction, described by the Bacteriophage Adherence to Mucus (BAM) model, allows phages to kill invading bacteria before they reach epithelial cells. This non-host-derived immune barrier enhances protection in the gut and respiratory tract.

Lysogenic conversion occurs when bacteriophages integrate their genome into bacterial DNA, carrying beneficial genes for antibiotic resistance or specialized metabolism. These genetic transfers alter the stability and resilience of the gut microbiota, particularly under selective pressures such as antibiotic exposures. This lysogenic lifestyle promotes horizontal gene transfer, enhancing microbial adaptability and maintaining ecological balance.

Some bacteriophages enhance bacterial pathogenicity by injecting virulence genes into bacterial genomes. For example, the CTXϕ bacteriophage injects genes encoding cholera toxin into Vibrio cholerae. Strains lysogenized by CTXϕ become pathogenic, produce cholera toxin, and infect the host gut epithelium, demonstrating how prophage-mediated gene transfer can convert harmless bacteria into pathogens.

Bacteriophages represent the most abundant viral entities in the human virome, with many belonging to orders such as Caudovirales and Microviridae, while a substantial proportion remains unclassified as viral dark matter. Beyond localized effects in the gut, emerging evidence suggests an intra-body phageome where phages translocate across epithelial barriers into blood and lymph, potentially contributing to immunomodulation throughout the body.

Bacteriophages influence microbial fitness through prophage-mediated gene exchange, which significantly affects bacterial adaptation and host-associated microbial homeostasis. By carrying and transferring genes for antibiotic resistance and specialized metabolism, phages enhance bacterial adaptability. This genetic exchange maintains ecological balance in the gut rather than causing immediate bacterial lysis, promoting a stable microbial community.

Bacteriophages in the human body belong to various taxonomic orders, with Caudovirales and Microviridae being well-characterized groups. However, a substantial proportion of bacteriophages remains unclassified, referred to as viral dark matter. These diverse phages occupy different ecological niches throughout the body, from the gut to mucosal surfaces, each contributing distinct functions to the human virome.