Do diseases have microbial fingerprints?

Although faecal transplant can save the lives of people with C. diff infection, its application in other contexts has been slower to take off. A lack of healthy donors is one of the reasons. As Nibil Quarashi mentioned, only 5% of volunteers make the cut to become stool donors, and an application form online highlights why… To be regarded as “healthy”, individuals must have no history of gut problems, allergies, recent asthma, and even treatment for depression and anxiety. The reason for such stringent criteria is we are still unclear about how the microbiome contributes to all of these other conditions. Studies have begun investigating if there is a gut microbiome “fingerprint” for a host of different diseases - ranging from IBS to anxiety disorders and even Parkinson’s disease - to see if the gut could be used as a novel avenue for those next generation microbiome therapies. Andrew Page, Head of Informatics at the Quadram Institute which specialises in gut health, microbiology and food, told Julia Ravey about how we can find these fingerprints and why we still need to exercise caution…

Andrew - What people do is they do case control studies, so they look at someone with a disease or an illness, and then they look at people who are normal, maybe who live in the same area, same households, and they try and look for differences. So you get all the DNA from their poo and then you try and work out what species are in one and on the other. And it's only when you do this kind of on a large scale, you can start to see signals coming through. But it's a very new area and a lot has changed over the past few years. And I think it's gonna keep us occupied probably for the next 20 years, because there's so much inside us that we don't really know. If you take a normal person randomly off the street, they're probably gonna have novel species that we've never seen in the lab or grown in the lab and studied in depth.

Julia - So it sounds like it's very early days in terms of looking at if there are certain microbes potentially involved in different diseases, but so far, what diseases have shown some of these potential relationships?

Andrew - So people have said, okay, maybe Parkinson's disease has a relationship with the microbiome. This has been reproduced with multiple studies so maybe there's something there. But what we don't really fully understand is what's causing it. And is this just a signal of someone with Parkinson's has a different type of microbiome or is it something that's actually real and is there, and is a real signal. So when they've gone and done studies, they've consistently found signals where there's more lactobacillus and there's more bifidobacterium within the guts of people with Parkinson's versus not. But then the caution there is that lactobacillus is something that's very commonly found in yogurt. I can tell you now, yogurt that you buy in the supermarket is not gonna cure you of all your ills, but bifidobacterium is quite interesting because they've looked in other studies and they've found that it has a beneficial impact. So when they gave it to pre-term babies, they found that actually the rates of sepsis and other diseases like that have gone down simply by introducing some of these bacteria.

Julia - And so if we're looking towards many different diseases and trying to find a microbiome signature, how can you tell if the microbes that have changed is a consequence of the disease itself, or if it's causing the disease. Can you tell that from looking at DNA alone?

Andrew - Not from DNA alone, this is where you need heavy duty statistics and a lot of other experimental work. So if you just look at the DNA alone, the most common experiments people do is they look at 16S which is just a short region that's conservative bacteria. And they'll do a very high level and they'll say, 'oh, this genus is there. And it's in these numbers'. And then with a different person it's in different proportions. And that gives you kind of a high level overview, but that's kind of like trying to learn French by standing on the Cliffs of Dover with binoculars. You know, you can only tell so much. Genome sequencing allows you to go in further depth, but really the key is where you can pull out a bug, you can figure out how to grow it, and then you can actually go and do experiments on that individual bug. But then it gets more complicated because, within our gut, you might have hundreds of species living together in harmony, and each provide different things for each other. You're not just looking at one bug, you're looking at maybe 10 bugs in combination. And that's quite a difficult challenge. A lot of science is focused just on pathogens and things that make us sick, but it hasn't focused on all the other commensals, things that don't make us sick. And those have just been kind of ignored because there is no funding for research in those, yet those are the things that keep us healthy or keep pathogens at bay. And they make up the vast bulk of all the bacteria that are right there inside us. But we don't really know what they do.

Julia - So with DNA sequencing, do you think that right now, we're still at that phase where we're just trying to identify candidates and then get those candidates into a lab and try to understand essentially what they do before jumping into this is causing this disease? And this is how we're gonna manage it and treat it?

Andrew - Yeah. I mean, there's a lot of snake oil salesmen out there and they are jumping on this, like they've jumped on many other things. And they said, 'oh, you know, the microbiome is the latest, greatest thing. Give me lots of money and buy my cocktail and then will cure everything out there'. And, you know, I've heard a lot of crazy stuff. Unfortunately, a lot of it is gonna just turn out to be hype and then people have moved on to something else. What we do know is that actually, in some cases, if you add in a bacteria it can improve, say, how drugs are absorbed in the system, or it can improve other aspects. So there are definitely positive benefits there. So I think we actually have to figure out what is actually really impacted and what is not. And there's a lot of false routes that we can go down. So people have, say, found a microbiome in the placenta, but then other people have found that that's just contamination. But we absolutely do know that there is so much inside us that we don't know. And as we unpick it, and as we deconvolute all these complexities and how they work and what they produce, we'll find a lot more interesting stuff. And the goal is, in the future, that you can just take a pill with some bacteria in it, and then that'll maybe cure an illness or it'll make a drug more effective. It could lead to a whole new area of treatments for people to make you healthier and live longer, you know, in a much more healthier way.