How gut viruses shape your gut microbiome

Famously, your gut microbiome is teeming with trillions of bacteria. But these bacteria are not alone.

Your gut also contains fungi, protozoa, archaea, and viruses. We recently covered the fascinating world of your gut fungi — the gut mycobiome

But today, we’re focusing on your gut virome: the viruses that call your gut home.

Scientists are still grappling with the immense complexity of how gut bacteria influence your health. But for links between gut viruses and health, we have even further to travel, as they’re still relatively mysterious.

In this feature, we’ll describe your gut virome and how it influences your gut bacteria in surprising ways.

What’s the gut virome?

Let’s start with a fact that will, quite possibly, blow your mind. You have trillions of bacteria in your gut, that’s already pretty surprising, but — hold onto your hats — the viruses in your gut might outnumber bacteria 10 to 1.

So if gut bacteria influence your health significantly, it makes sense that gut viruses will, too.

Next, let’s bust the myth that all viruses are “bad.” 

When you hear the word “virus,” you might think “disease.” But most of the viruses in your gut don’t (in fact, can’t) infect you or make you sick.

The majority of viruses in your gut  — around 90% — are called bacteriophages. Translated, that roughly means bacteria-eaters. They get this name because they only kill bacteria. 

Scientists commonly shorten their name to “phages,” so we’ll use that term throughout.

And here’s another impressive fact: Experts believe that phages are the most numerous organisms on earth, which is quite the accolade.

Other viruses living in your gut include types that do infect human cells and also some plant viruses, which mostly enter through your food or environment.

Like the bacteria in your gut, your gut virome is personal to you. And in adults, it seems to be fairly stable over time, like your population of gut bacteria.

What are phages up to?

As we mentioned, phages kill bacteria. And they’re fussy eaters — each type of phage only “eats” a small range of bacteria.

Because they only target specific bacteria, some researchers are investigating whether they might be a valuable replacement for antibiotics. They hope that phages could help us tackle antibiotic-resistant strains. 

In fact, scientists first started looking at so-called phage therapy a decade before the discovery of the first antibiotic, penicillin. But that’s a story for another time. 

As natural predators of bacteria, phages can help shape your microbiome in the same way that predators help control population numbers of prey animals. 

Again, we know that gut bacteria are important for health, so anything that can influence them is likely to affect your health, too.

Aside from the predator–prey relationship, phages can also give bacteria new abilities and powers.

To understand how phages do this, we need to dig into their lifecycle. It’s a little complicated in parts, but it’s fascinating, so it’s worth covering.

The lifecycle of a phage

As part of their life cycle, phages inject their genetic material into bacteria. Once inside, it hijacks the bacteria’s cellular machinery and starts making new phages.

Once the new phages are created, they burst out of the bacterial cell, killing it. This is called the lytic cycle.

Alternatively, phages can enter the lysogenic cycle, which runs like this: 

Once the phage has injected its genetic material into the host bacterium, it integrates its genes into those of the bacterium. This mix of bacterial and viral genes is called a prophage.

As the bacterium divides and replicates, the phage’s genes are replicated, too. And because their genome is small and these viral genes don’t interfere with the bacterium's genome, the bacterium doesn’t seem to mind and continues its life.

But if conditions become less favorable, for instance, if there aren’t enough nutrients around, the prophages become restless. 

They extract themselves from the bacterial DNA and enter the lytic cycle outlined above, killing the bacteria. 

Sometimes, when the prophage extracts its genes from the bacterium’s genes, it accidentally takes sections of the bacteria’s DNA with it. 

Then, when the newly hatched phages enter another bacteria, they carry these sections of bacterial genes, which can become part of their new host’s genome. 

This is called horizontal gene transfer, as opposed to vertical gene transfer, where genetic information is passed from parent to child.

So, phages don’t just kill bacteria. They also insert viral genes into bacterial genes. And they take sections of bacterial genes and spread them to other bacteria, including bacteria from different strains.

In short, phages can share their genes with bacteria and share bacterial genes with other bacteria.

Phage vs. bacteria

The shuffling and sharing of genetic information described above can influence how bacteria behave, their ability to survive, and more. Next, we’ll look at a few examples of this.

Acid resistance

Some phages can affect how well a bacterium survives. For instance, one study found that when one particular phage infects the bacteria Escherichia coli, it makes them more resistant to acid.

This, the authors suggest, might help them survive better in your gut.

Cholera

Some strains of a species of bacteria called Vibrio cholerae produce the cholera toxin, which causes cholera. However, not all strains of V. cholerae produce this toxin. 

But when the cholera toxin phage infects them, it inserts toxin-producing genes into the bacteria’s genome. This turns an otherwise relatively harmless bacteria into a potentially deadly one.

Building biofilms

Biofilms are tight clusters of bacteria that are attached to each other and any available surfaces. 

Being a part of a biofilm helps bacteria avoid a host’s immune system and survive in harsh environments. Certain phages can help bacteria form biofilms

Some phages, on the other hand, can break apart biofilms. According to scientists, one day, we might harness this ability to treat persistent infections. 

Antibiotic resistance

Horizontal gene transfer — where phages accidentally shift genetic information from one bacteria to another — can also boost bacteria’s survival by sharing antibiotic-resistance genes

While good news for bacteria, this is bad news for humans.

Sharing enzymes

As a final example, a recent study looked at Bacteroides, a common form of gut bacteria. 

The researchers found that a particular enzyme helps these bacteria thrive in your gut. And once again, the genes responsible for that enzyme enter the bacteria thanks to a phage.

So phages aren’t just killing machines, they can influence your gut bacteria in a variety of ways.

They can break up or form communities of bacteria, help bacteria survive better, and share useful genes between different strains.

As the authors of a review write, these viruses “contribute to the functionality, adaptability, stability, and consequently evolution of the bacterial communities within the human gut.”

Phages and your health

We’ve only scratched the surface of the many roles that phages might play. But already, you can see that they’re likely a significant influence on your gut microbiome.

Of course, there are many outstanding questions. And studying viruses is incredibly challenging, so it will be a long time before we understand how they influence health and disease.

However, scientists have already found links between phage populations in your gut and some health conditions. 

At this stage, we don’t know whether changes in phage populations cause these conditions, but researchers have found some intriguing correlations. We’ll briefly cover a few next:

Inflammatory bowel disease (IBD): Scientists have found that people with IBD have a less diverse range of gut bacteria than those without IBD. Conversely, they have an increased number of viral species.

Type 1 diabetes: One study recruited children at risk of developing type 1 diabetes. The scientists found that, compared with children who didn’t develop type 1 diabetes, those who did had a less diverse gut virome before they developed the condition.

Obesity and type 2 diabetes: A study in China found that people with obesity, and particularly people with obesity and type 2 diabetes, had a less diverse gut virome than people without either.

Alcohol-associated liver disease (ALD): Scientists have found that the gut virome of individuals with ALD differs from those without the condition. And certain virus strains are linked to disease severity.

Colon cancer: People with colon cancer have a more diverse gut virome. And changes in the gut virome are linked to different stages of cancer.

As we mentioned above, these are associations. So, we don’t know whether gut viruses are driving these conditions or whether viral populations are changing in response to other factors linked to the condition.

Gut virome research is still in its infancy. But one thing’s for sure, it’s a fascinating and challenging subject. 

And hopefully, in the future, we’ll be able to harness these minuscule organisms to help support human health and fight antibiotic-resistant bacteria.

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