Microbes vs. Phages: America’s Gut Issues

Amber Dance and knowablemagazine.org introduce us to the phageome

The lining of the gut should look like a shag rug, but as most colonoscopies find, it's a smooth tube like a water hose due to eating gluten that kills the cilia that allows us to absorb nutrients (Oleksand Troian/Moment/Getty Images).

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America is too fat, like this obese specimen.

Most have probably heard of the microbiome — the collection of probiotics, hordes of harmful bacteria, and other tiny life forms that live in our guts. Well, it turns out those bacteria have viruses that exist in and around them — with important consequences for both them and us.

Hey, microbiome, meet the phagosome. There are billions, perhaps even trillions, of these viruses, known as bacteriophages (Greek for “bacteria eaters” in Greek) or just “phages” to their friends, inside the human digestive system.

Phageome science has skyrocketed recently, says Breck Duerkop, a bacteriologist at the University of Colorado Anschutz School of Medicine, and researchers are struggling to come to grips with their enormous diversity.

Don't try to shame my obesity. I'm just big bellied.

Researchers suspect that if physicians could harness or target the right phages, they might be able to improve human health.

“There will turn out to be good and bad phages,” says Paul Bollyky, an infectious disease physician and researcher at Stanford Medicine. But for now, it’s still unclear how many phages occupy the gut — perhaps one for each bacterial cell or even fewer.

There are also bacteria that contain phage genes but aren’t actively producing viruses; the bacteria are just living their lives with phage DNA tagging along in their genomes. And there are lots of phages still unidentified; scientists call them the “dark matter” of the phagosome.

A big part of current phage research is to identify these viruses and their host bacteria. The Gut Phage Database contains more than 140,000 phages, but that’s surely an underestimate.

How do these gut bugs impact behavior?

“Their variety is just extraordinary,” says Colin Hill, a microbiologist at University College Cork in Ireland. Scientists find phages by sifting through genetic sequences culled from human fecal samples.

That’s where researchers found the most common gut phage group, called crAssphage. (Get your mind out of the gutter — they were named for the “cross-assembly” technique that plucked their genes out of the genetic mishmash.)

In a recent study, Hill and colleagues detailed a light-bulb shape for crAssphages, with a 20-sided body and a stalk to inject DNA into host bacteria.

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How to counter an infestation of invaders?

It’s not clear whether crAssphages make a difference to human health, but given that they infect one of the most common groups of gut bacteria, Bacteroides, Hill wouldn’t be surprised if they did.

Other common groups that also infect Bacteroides include the Gubaphage (gut Bacteroides phage) and the LoVEphage (lots of viral genetic elements). Phageomes vary widely from person to person.

They also change depending on age, sex, diet and lifestyle, as Hill and colleagues described in the 2023 Annual Review of Microbiology.

Though phages infect bacteria and sometimes kill them, the relationship is more complicated than that. “We used to think that phage and bacteria are fighting,” says Hill, “but now we know that they’re actually dancing; they’re partners.”

• Amber Dance and Knowable Magazine, Inverse via MSN, 8/18/24, The microbiome’s forgotten cousin could be key to solving America’s gut issues (MSN); Eds., Wisdom Quarterly