Bacteriophages or phages are viruses that infect bacteria and represent the most abundant genetic entities on Earth, outnumbering all others by roughly ten to one. Among them the prototypical crAssphage (p-crAssphage) stands out as one of the most common phages in the human gut, present in people worldwide. Yet, for over a decade, its lifestyle remained a mystery scientists were unable to grow it outside the body or identify the specific bacterial host it relied on.

In this Q&A, the team discusses how they solved a long-standing scientific puzzle what sets p-crAssphage apart, and how their discovery could deepen our understanding of the viruses that inhabit the human gut.

Bacteriophages that infect bacteria can influence their hosts in multiple ways. While some act as simple predators, others establish surprisingly complex and sometimes even mutually beneficial relationships. Within the gut, phages play a major role in shaping the composition, diversity, and functions of bacterial communities.

One clear effect is bacterial lysis, where phages kill specific bacteria. This can have direct consequences for human health depending on whether the target is harmful or beneficial. For instance, destroying Salmonella enterica, a leading cause of foodborne illness, can help prevent infection, whereas eliminating a helpful bacterium such as Bacteroides fragilis important for vitamin K production and immune regulation may disrupt vital physiological processes.

Yet phage influence reaches far beyond bacterial killing. Many can insert their genetic material into bacterial genomes, altering metabolism, toxin production, or stress resistance. These changes affect how bacteria interact with each other sometimes encouraging cooperation and other times fueling competition. They also shape how bacteria communicate with the human immune system with outcomes ranging from reduced inflammation to heightened immune activation.

P-crAssphage is one of the most widespread and abundant phages in the human microbiome present in people across the globe. First identified in 2014 through DNA sequencing of human stool samples it has long resisted laboratory study researchers have been unable to consistently grow it outside the body or isolate it in a test tube. Early attempts hinted at an unusual life cycle showing that p-crAssphage does not readily kill its bacterial host and may instead maintain a more cooperative relationship. Despite its dominance in the gut it has remained largely inaccessible to detailed investigation in the lab until nowUnlike typical phages that kill their hosts and form visible plaques on Petri dishes p-crAssphage produces few viral particles and keeps most of its DNA inside bacterial cells escaping standard detection methods. As a result, such phages have remained largely unstudied despite being common in the human gut. Developing new ways to identify and grow them is essential to reveal how they shape bacterial communities and potentially impact human health.

Source: https://med.stanford.edu/medicine/news/current-news/standard-news/crassphage.html