CrAssphage

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CrAss-like phages, also called crAssviruses, are a very common group of viruses that infect bacteria in the human gut. They were first found in 2014 when scientists analyzed stool DNA from many people and noticed a new, widespread type of virus. They mostly target Bacteroidota bacteria, especially Bacteroides species. The first crAss phage that could be grown in the lab, crAss001, was isolated in 2018 from a Bacteroides intestinalis host.

Structure and identification
CrAssviruses are podoviruses, meaning they have short, non‑contractile tails and icosahedral (spherical) capsids (the protein shell). The first 3D image of a crAss phage was solved in 2023, helping scientists understand how these particles look and how they might attach to bacteria.

How common they are and what they do
CrAss-like phages are among the most abundant viruses in the human gut and are found in many people worldwide. They are not clearly linked to any specific health problems and are generally thought to be a normal part of a healthy gut microbiome. Their presence is often connected to the gut bacteria they infect, especially the Bacteroidota group.

Discovery methods and a typical crAss phage
CrAss phages were discovered using a cross-assembly approach. The first representative, p-crAssphage, was built from fragments that repeatedly appeared across many people’s gut metagenomes. Its genome is about 97,000 base pairs in a circular DNA circle and contains roughly 80 predicted genes. Researchers predict crAss phages infect Bacteroidota bacteria, which are common in the gut.

How crAss phages live with their hosts
Initial ideas about crAss phages suggested various lifestyles (passing between host and phage as either lytic or lysogenic). In the lab, crAss001 and its B. intestinalis partner show a surprising relationship: they can coexist and replicate together in liquid culture, but the phage can still kill the bacteria on solid surfaces. Because crAss phages lack typical lysogeny genes, scientists think the stable coexistence may come from the host bacteria changing their surface capsules (a process called phase variation). This creates subpopulations: some susceptible to infection and some resistant, allowing the phage to persist while the bacteria keep growing. CrAss002 shows a similar pattern with its host, B. xylanisolvens. When grown in gut-like communities, the phages and bacteria can maintain steady levels rather than one completely taking over.

Where they live and how they spread
CrAss-like phages are not just in the human gut. They’re found in other environments too, including termite guts, soil and groundwater, soda lakes, marine sediments, and plant roots. There are related groups, such as gubaphages, that are also common in the gut.

Transmission and practical uses
CrAss-like phages are thought to pass from mother to child, though they are usually rare at birth and become more common during the first year of life. They can also be spread through fecal microbiota transplants (FMTs). Because they are so abundant in human guts, crAss-like phages are sometimes used as markers to detect human fecal contamination. Their presence doesn’t currently indicate health problems, but their absence might be linked to certain conditions, like metabolic syndrome, in some studies.

Interesting notes
One crAss phage, phi14:2, has an RNA polymerase that looks similar to enzymes involved in RNA interference in animals and plants. This has led to ideas that parts of eukaryotic RNA interference could have phage origins. Overall, crAss-like phages are a large, diverse, and mostly harmless group that play a role in shaping the gut bacterial community and have a long and broad presence in nature.