Parasites and the ageing process
“We’re ageing faster and afflicted by allergies and inflammatory diseases because we’re living lives that are too sterile and divorced from the parasite-laden existence we evolved to encounter.” Or so says the “old friends” hypothesis, that posits that putting back some of these microbes and other organisms might be a way to achieve a turnaround in what are burgeoning rates of diseases like asthma. Bruce Zhang is an undergraduate at University College London and - prompted by Covid-19 - has been devoting what would otherwise be time for benchwork to hitting the immunology literature, as he told Chris Smith...
Bruce - Something that sort of came out of the pandemic actually, because a lot of the lab work was shut down due to restrictions of people being physically in the lab. So we thought about how we could perhaps do some research on our computers at home, and one of the ways is conceptual research where we just kind of read into the existing literature of published works and then see whether we can test new hypotheses using what is already published. And one of the ideas in the lab where I'm working is whether helminth parasites, which are these kind of worms that live inside our bodies, could actually protect against certain diseases of ageing.
Chris - Because, for a long time, people have suggested, and it's called the hygiene hypothesis isn't it, that perhaps our obsession with sterility in the modern era is the root of many of the diseases of affluence that we see around us today, and foremost among them inflammatory conditions - asthma, allergies, and so on
Bruce - Exactly. Throughout human history and evolutionary history we've grown and evolved with all these parasites and bacteria inside our bodies. And now suddenly we're removing them from our bodies due to being more clean and hygienic. So that suggests that perhaps there is an imbalance in our microbial "old friends", you could call them
Chris - Is there actually any evidence to backup these hypotheses though? Is it just a good story that tends to get better in the telling, or are people actually subjecting this to decent scientific scrutiny and there is fruit being born out of these endeavours?
Bruce - Yeah, there's actually quite a bit of evidence suggesting that a loss of these parasites and other microbial species is actually causing increased rates of diseases, such as inflammatory diseases, autoimmune diseases. Common examples are multiple sclerosis, rheumatoid arthritis, even allergies like eczema, asthma, all of these. There's quite a bit of evidence showing not only epidemiologically but also in clinical studies and experimental work using model organisms, such as mice, when they give these mice these parasites, they actually become protected against many of the symptoms of these inflammatory diseases.
Chris - Is this association though, or causation, because is it that something else is actually changing the risk profile for these diseases? And it's something that the worms go along with rather than causing? Or is there a sort of biologically plausible reason why things like worms could be influencing the disease course of things like rheumatoid arthritis?
Bruce - Obviously it's quite a complex issue when you're looking at what the actual protective mechanism is on the biological level. But there is lots of evidence that there is an immune role when these infections are happening. And it seems to be suggesting that yes, it is a causal rather than just correlative relationship and much of this is grounded in evolutionary theory because humans live together with these parasites. And obviously the host organism wants to expel these parasites and these bacteria or other pathogens from the body. And so what the apparent pathogens and parasites do is to try to suppress the host immune response, so they shut down the immune response a little bit so that they aren't killed by the host. And so that could be one way. It's very plausible that they would be modulating the immune system of the host and perhaps causing the changes in the immune response that we observe.
Chris - What sorts of evidence have we got that that's going on?
Bruce - There're actually many examples of mouse models where people would just test different types of parasites. For example, there's a pig whipworm that normally affects pigs called Trichuris suis, and one way is to take their eggs and give them and also the proteins found on the surface of the eggs to these mice, and it does show a beneficial effect against inflammatory diseases. Many other similar conditions have been tested and there's quite extensive literature on this now.
Chris - Is it actually molecules coming out of the parasites that directly impacts the immune system? Or is it that the parasites do something to the microbiome at large, the assemblage of microbes we have in us and on us, and it's the microbes changing that affects the disease course? Or is it both?
Bruce - From what has been published it's probably both. There's definitely evidence that there are molecules that are directly secreted from these parasites that could directly modulate the immune system of our bodies, but also they could be doing that indirectly by first modulating the microbiome, perhaps in the gut. It's been shown that the gut actually is quite sensitive to the composition of bacteria in there. So if you change the composition of bacteria, you change the health of the gut lining, and that can actually lead to large-scale systemic changes in the body. So if these parasites could change this composition of the gut bacteria, then that could affect health.
Chris - How would you see this learning being deployed? Because many people will be uneasy about the prospect of being infected, or at least colonised with a whole assemblage of worms and possibly other parasites to control the ageing process or control their disease. They probably feel a lot more comfortable if you said, well, we can juice these worms and get whatever they make to control the immune system out and give that as a pill instead. Where do you see this going?
Bruce - At the moment there's actually a lot of research groups looking into the specific molecules and proteins that are found on these parasites because people are definitely a little bit disgusted by the prospect of putting live ones into their bodies. So there is a lot of research going in that direction to just isolate the responsible proteins only so that we don't have to have actual worms in our systems. Of course it could be argued that live worms are more effective. They obviously have the whole panoply of molecules that are required for this protective effect. But I suppose as research goes on and as we identify more and more of what the actual molecules are, then we can move towards a more friendly option.