There has been a lot of news lately about the bacteria living in our gut—the human gut microbiome. Researchers are learning which bacteria live there, who is naughty and who is nice and even a somewhat distasteful way to replace naughty with nice (a fecal transplant).
What gets lost in all of this is the fact that these bacteria are wild creatures whose only purpose is to divide and spread. If given half a chance, even those helpful bacteria would break free of the gut and spread through the body, eventually killing its host. To properly harness their power for good, we need to have ways to control them.
A new study presents an unexpected way that we work with viruses to keep bacteria confined to the gut. The idea is based on the fact that the mucous which lines the inside of our gut is riddled with viruses that infect and destroy bacteria (these viruses are called phages). If a bacterium gets too far into this mucous layer, it meets with a phage that destroys it. It is like a minefield of viruses set to explode whenever they encounter a bacterium. Except that it is even better than that...it is a self-renewing minefield.
When a phage infects a bacterium, it first hijacks the bacterium’s cellular machinery and forces it to crank out lots of new virus particles. Once the bacterium has made as many virus particles as it can, the bacterium then explodes releasing lots more phage into its surroundings. Now there are more phage that can infect any bacteria bold enough to venture where they shouldn’t.
This is a win-win for both the phages and us. We get to keep helpful bacteria confined to where they can do some good and the phage get a plentiful supply of bacteria. In fact, it is such a good deal for the viruses that they have evolved tails that can hook onto the ends of the mucin molecules in our mucous layer. This allows the viruses to linger for a longer time, increasing their chances of latching onto a bacterium.
So the mucous layer is like a huge three-dimensional forest of hooks with phages hanging off of them, waiting for passing bacteria. Well, this is almost the right analogy. The phage don’t stay on the hook for long but instead pause for a bit at each hook. The researchers hypothesize that these pauses are a big enough boost for finding bacteria that there has been a positive selection working on the phages for interacting with the mucins. Or in other words, those phage that could stick to the mucins did better than those that could not so that now the vast majority of phage have these sticky tails.
Now of course, nothing in biology is as simple as this. There are lots of different kinds of phage, each specific for a certain bacterial species. And the mucous layer isn’t as static as I have painted it here either. The cells lining the gut, the epithelium cells, are constantly making new mucins and the old ones are being sloughed off with phage being sloughed off along with them.
But even with all of this added complexity, what we have is a situation where viruses are potentially being helpful instead of harmful. And this probably isn’t true just in people either. Mucous layers in a wide variety of organisms from corals to mammals all seem to be enriched for phage as well.
It may be that this sort of primitive immune system is common in nature. In this system, creatures harness phages to destroy invaders instead of using their own genes to generate cells akin to our killer T cells. They use phages to create a non-host immune system.
We’ll need to do a lot more research to see whether the phage in our gut really are a line of defense and how common this system really is in nature. But whatever the final answer, it has got us to thinking about immunity in a whole new way. This might open up avenues of research we hadn’t even thought about before.