Bacteriophages of the Human Virome

Bacteriophages are found throughout the human body. They may even outnumber eukaryotic viruses, forming an important and dynamic component of the human virome. Indeed, phages represent the most abundant viral entities, with densities in the gut reaching up to 10⁹ particles per gram of fecal matter, and many belonging to orders such as Caudovirales and Microviridae, while a substantial proportion remains unclassified as viral “dark matter.”

Lysogeny and Genetic Exchange

In the gut, bacteriophages may integrate their genome, carrying beneficial genes for antibiotic resistance or specialized metabolism into the bacterial genome through lysogenic conversion. These genetic transfers may 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 rather than causing immediate bacterial lysis. Such prophage-mediated gene exchange can significantly influence bacterial fitness and host-associated microbial homeostasis.

Mucosal Defense Mechanisms

On mucosal surfaces, bacteriophages bind via capsid proteins to mucin glycoproteins, concentrating at the epithelial barrier and forming a defense against invading bacteria. These phages can kill the invading bacteria before they reach epithelial cells, protecting the host. This interaction is described by the Bacteriophage Adherence to Mucus (BAM) model, where immunoglobulin-like domains on phage capsids facilitate binding, establishing a non-host-derived immune barrier that enhances protection in the gut and respiratory tract.

Pathogenic Conversion and Systemic Presence

Some bacteriophages enhance bacterial pathogenicity. 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. Beyond localized effects, emerging evidence suggests the existence of an intra-body phageome, where phages translocate across epithelial barriers into blood and lymph, potentially contributing to immunomodulation and antimicrobial surveillance throughout the body.