The virome: How viruses shape your gut health

You’ve likely heard of your microbiome, but have you heard of your virome? Your virome is the suite of viruses living in your body. And just like bacteria and fungi, they play a role in your health.

A small number of them come from the viruses that infected you throughout your life. But most of them are viruses that infect bacteria known as bacteriophages, or phages. Both have an affect on your gut health.

The extraordinary thing about the virome is that it injects an even greater level of complexity on an already infinitely complex system. Whereas your gut microbiome contains thousands of bacterial species, your virome contains hundreds of thousands of viruses.

So today, we’ll cover a bit of the basics to keep it simple. Let’s begin with what is a virus?

What is a virus?

You may not be aware of this, but viruses aren’t living things. Viruses are simply transport systems for genetic information to deliver to hosts.

Since viruses aren’t alive, they can’t make more copies of themselves. As a result, viruses are dependent on a host’s cellular machinery to replicate themselves.

So they infect host cells and use them to become virus generating factories. Some viruses are RNA viruses, and some are DNA viruses. An RNA virus simply enters the cell cytoplasm, releases the RNA, and uses the host cell’s organelles to make copies of itself.

On the other hand, DNA viruses enter the cell nucleus, release DNA, and replicate. We won’t go into terrible depth here, but unlike RNA viruses, DNA viruses use our cellular machinery to make RNA, which then tells our organelles to make more virus. To do this, they have to enter the cell nucleus, where a host’s DNA resides

In both instances, the virus hijacks our cells to make them virus factories.

The virome: The bad

When we think of viruses that infect humans, we don’t think of anything good happening. For the most part, this is true.

Viruses such as SARS-CoV2, Epstein-Barr virus(EBV), and herpes simplex virus(HSV) can infect the gastrointestinal tract. This can lead to acute or long-lasting GI symptoms, for a couple of reasons.

Both EBV and HSV are DNA viruses that can enter a period of latency. Basically, they hide out undetected in cells, and begin ramping up production during times when the immune system become compromised. Reactivation can lead to colitis for both viruses.

We don’t know if SARS-CoV2 becomes latent or not. However, there is evidence that people who develop a SARS-CoV2 infection that goes on to long haul COVID also develop longer term disorders of gut-brain interaction(DGBI).

One paper found that 66% of longhaulers developed at least one DGBI, with 75% being new onset DGBIs. This may be due to a persistent infection, or it could be due to permanent changes induced by an initial, but resolved, infection.

For example, we discussed how alterations in the microbiome are related to long COVID in a blog you can check out here. Changes to the microbiome caused by the initial infection may drive these DGBIs, we simply don’t know.

In much the same way, when a phage infects a beneficial member of our microbiome, it may alter it’s behavior in a way that makes it less healthy, or worse, unhealthy altogether.

The virome: The good

It’s not all doom and gloom when it comes to viruses, even the ones that infect us. One paper found that giving antibiotics to mice depleted their microbiome, impairing their immune system and the villi in their intestine, which helps absorption.

Exposing the mice to norovirus caused their gut to become healthy again. It did this by compensating for impaired type 1 interferon signaling. Effectively, the virus picked up the slack for the lost microbes.

Another paper found that there are disease-promoting and disease-protective viruses. They found that infecting mice with viruses from humans with IBD created gut inflammation in the mice. On the other hand, mice infected with viruses from humans without IBD were protected against inflammation.

Other evidence shows that the presence of phages in mucus protects us against deadly microbes. The phages attach to the mucus layer and help protect mucus-producing cells from becoming damaged by pathogenic bacteria.

By infecting and killing specific types of bacteria, phages can select for healthy gut microbes. In essence, they are functioning as part of our immune system.

We can use phage therapy to better target and kill specific pathogenic bacteria; a better option than broad spectrum antibiotics. On the other hand, we could use them to confer beneficial traits to bacteria to improve the microbiome.

In this way, two people could have the same microbione at the bacteria level, but these bacteria may function differently depending on the virome of the individual.

Image source

Putting it all together

As you can see, this creates more complexity. We have viruses, both the kind that infect us as well as our microbes, selecting for the microbiome. Conversely, the microbiome likely selects for the viruses we are susceptible to, and that can infect our microbes.

Then, of course, our internal state is important as well. Genetics certainly plays a role in how our immune system functions and the viruses we are susceptible to. Additionally, our external environment regulates which viruses we are exposed to.

And finally, the current state our body is in plays an important role in how susceptible we are to disease. Maintaining a healthy lifestyle by exercising, eating a healthy diet, managing stress, and prioritizing sleep are important for preventing viral infection, as well as preventing latent infections from reactivating.

While we certainly don’t know for sure, it seems logical that health-promoting habits may also promote a healthy virome. It’s essential to create an ecosystem that promotes balance for there to be balance between our microbiome, our virome, and us.

But in the event that something goes sideways, whether from random exposure to a human virus or phage, understanding the virome will lead to better diagnosis and treatment of conditions that we currently have trouble treating.

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