Instant Genius - Faecal transplants, with Dr Benjamin Mullish

Episode Date: October 2, 2022

The Food and Drink Administration in the States has recently recommended the use of faecal transplants to treat various bacterial infections. We spoke to Dr Benjamin Mullish, a researcher at Imperial College London’s Department of Metabolism, Digestion and Reproduction, about this promising new technique. Hosted on Acast. See acast.com/privacy for more information. Learn more about your ad choices. Visit podcastchoices.com/adchoices

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and high-end materials, delivering digital precision with analog warmth, so you can experience exceptional sound at home. Music just as the artist intended. Visit name audio.com to learn more. Hello and welcome to Instant Genius, a bite-sized master class in podcast form. Each week you'll hear world-leading scientists and experts

talking about the most fascinating ideas in science and technology today. I'm Jason Goodyear, commissioning editor at BBC Science Focus magazine. In this episode, I talk to Dr. Benjamin Willis from Imperial College London's Department of Metabolism, Digestion and Reproduction. He tells me about the promising new science of faecal transplants. Okay, so first off, when we're talking about fecal transplants, what exactly are we talking about? Okay, so this is a medical treatment whereby our primary aim is to restore the balance of all the billions of healthy bacteria that we have in our gut to people with particular conditions. And it's not just the bacteria, it's all the chemicals they produce, it's other viruses that live in our, in our poo, in our guts as well.

So we're trying to take the entire community and restore them to people with disease. And the reason we're doing that is because we think disturbances of the balance of these particular bacteria and the environment they live in is what contributes to a number of different diseases and particularly see difficile infection. So what we do is we're trying to get hold of the whole bacterial community from healthy people, to restore it to like a healthy person's. So we take a load of healthy people. We screen them intensively in the way that you would think of people who are blood-duty people. donors are screened. So they undergo a whole lot of questionnaires to check on their general health. We take a lot of screening of their blood and of their stool, take bloods of poo samples as well to check for their health, make sure they haven't got a number of wide range of different infections.

We keep them under close health follow-up. And we take poo samples from them, process them in the laboratory. So we try and get rid of anything we don't want any stuff that's in poo. We don't want. Food waste and other rubbish. What we do is we're trying to distill out and keep all the healthy bacteria and everything else around it and restore that into the gut. And there's a number of different ways in which we try and deliver that material into people. Some of that has been through endoscopies, using camera tests either from the top end or the bottom end of people. Some of that's been using fine tubes that we put up people's nose. And increasingly, it's in early days, but being increasingly used, we're able to actually get

the material into capsules, which obviously has a number of different advantages, but it's preferred bar patients because it's just easier, less invasive around. Yeah, so this sort of all centres around the significance of the gut microbiome. So can you tell me a bit about how significant that is to our health? Yep, so when people talk about bacteria in the gut, I think most people's initial instinct is to think about things that might have heard of like salmonella or things that calls food poisoning or those sort of things. But over the past 20 years or so, perhaps a little longer,

we've started to appreciate that there is this entire hidden ecosystem, hidden community inside of us, in which we have billions of bacteria, sometimes quoted as trillions of bacteria within our gut, and not just bacteria, a whole community, the chemicals they make, the environment they live, all sitting inside of us. And not just along our gut,

the term microbiome refers to sort of all the slimy surfaces, so in our saliva, the lining of our lungs, lining of our reproductive system as well, where we have all these bacteria living there and that have a huge amount of, increasingly we've realised have a huge contribution to our health. So it's been a sort of co-evolution, just as we provide an environment for these bugs that, you know, we keep the heating on, we keep them nice and warm, we keep the acid level of acidity, right? The feeling's mutual because we provides an environment for, they provide a lot of benefit for us,

whereby they provide particular chemicals that we use to provide us energy sources or to control our metabolism or protect us from infection or provide a huge different number of functions to keep us healthy. So we do some stuff for them and they do some stuff for us back. So we're talking about transplants here. So they come from a donor's gut? Yeah, exactly right. So we have this bank, most places that do fecal transplant have a,

have a bank of donors, so they're healthy people that were screening on a regular basis and collecting poo samples, collecting stool samples off them that we're using to actually make the material that were then transplanting into healthy people. So when you think of transplants normally, of course, people thinking of kidneys or livers or those sort of things. But of course, this is a bit more unusual because what we're talking about is taking what you would initially think of as waste material for one person. but actually using this as a sort of medical aspect to try and treat someone else.

Sort of following on from that, how do you determine that somebody has a healthy gut that is a viable donor? Yep, that's a really good question. So there is a long-running debate that hasn't been answered about how do we actually define what a healthy gut microbiota is? And there's lots of different ways you can start to try and answer that question. You can try and say which particular bacteria in there, however it's more complicated than that, because different bacteria do different functions in different environments and people with different diseases. You can start to look at some of the functions they do in terms of, say, particular chemicals they produce or particular proteins they produce. But again, that only gives us some degree of insights.

You can start to look at functions they do for us, the ways they interact with us as humans or as other animals to try and help us keep us healthy. But when it comes to actually in terms of fecal transplant, how do we select a good donor, we're still a question. quite an early stage. For most cases, we're trying to mitigate risk by trying to exclude people where we think they might have an adverse gut microboater or a risky gut microvoter, rather than particularly selecting out those who have a good gut microboater. So more specifically, we do a lot of screening to look for people with infections or to have problems with their guts, or we might exclude people, we're very meticulous about excluding people who might have

conditions that are associated with a particular gut microbiota. So for instance, we might exclude people with inflammatory bowel disease or who've had growths in their gut, or even people with a family history where they might have had polyps or cancers in their gut. But then it gets even more obscure than that, that lots of centres, us included, would even ask potential donors about if they've had depression or anxiety or other mental health problems in the past. So you might think why is that relevant. It seems pretty obscure at first why you do that. But this is a whole group of conditions where it's been associated with abnormalities or disturbances of gut microboater. And while this sort of treatment is in a sort of relatively early phase,

he's rather err on the side of caution and perhaps be a little overcautious on people we pick as donors than to be too laid back about it and then have to deal with consequences later. Yeah. Yeah, so I think sort of naturally some people are going to think that this is slightly unpleasant for one of a better better word when you make the transplant

is it just from one person's gut to another's without you know any treatment or so yeah so what we do in the process is this moment in time we'll get a donation

from a single donor and we will process that in the laboratory and then we've got the transplant material and then from the material we make from one person that is a sort of unit of fecal microboater transplant that we transplant into someone else. One good thing about using one donor and one material and one transplant is it means if there are any problems, if the recipient of the material had any issues, it's easy to try and establish the source. We can easily look back

and say, look, let's go back to that donor and the samples we got stored from them and ask them again about their health and see what's happening. However, another way of looking at it and another sort of theory that people have come up with is that maybe we should be what's called pooling donors. In other words, getting material and pulling it from a number of different donors. And the idea of that is that if you took a number of different people's donations and mix them together, so if there was a particular bacteria of benefit that's low in one person, you might compensate from that being there in the other person. And so by mixing it all together, you might have a sort of a richer community that collectively has a sort of bigger number of

functions and bigger number of bacteria than you would get otherwise. The problem with that cause, So say you transplant a mixed product into someone and they have a problem, you don't know which of your, you know, five donors or seven donors or whoever it is, might have had the problem, might have had a dodgy bacteria you wish haven't been there. So there's pros and cons both way. Yeah, so this is probably a bit complicated and maybe a bit looking too far forward. But is there ever, you know, a possibility that we could synthesize these bacteria, that we, you know, we can make them in the lab and then we can introduce them

into the patients. Okay, so yeah, you're exactly right. So I think what you're getting at here is saying that, you know, this is still a pretty crude process in what we're doing, and could we do something a bit more refined in what we're doing? So there's been a sort of number of different attempts of doing this, and what a lot of,

a number of different companies are doing is saying, look, we identify the bacteria in a fecal transplant that we think are responsible for how it works most of all. And could we, instead of just giving a whole fecal transplant, could we just give those bacteria together in some sort of mix, be that a capsule or some sort of drink or whatever it is, and administer that instead? And in fact, this year there were some trials from a reported in a large medical journal

of a trial of a sort of next generation of faecal transplant product where the material sort of had originally been derived from donors, but actually was a sort of spore product. So it was a sort of bacterial product that was sort of produced reproducibly in a lab without the sort of needs for ongoing donor material. And that seemed to work just as well as as antibiotics you would use to treat C. difficile infection. This product seems to work just as well.

So I think there's a new generation of products on the horizon that is saying, look, can we go beyond something as crude as fecal transplant and go on to something a bit more refined? However, there's still questions that remain. So for instance, if you think of people who need a blood transfusion, you know, you could split up a blood transfusion into saying we'll give you an iron infusion and we'll give you this molecule and that molecule that was in blood but no one's ever been able to make a synthetic blood. You know, we're still very reliant on people giving them blood donations of you know in this generation. So there might be something about the whole mixture. It might be something about

the whole community together. There's some element of the mixture that we don't understand at the moment that is beyond our understanding that works better than if we were just to try and reduce it down to its single components. But it's a really important ongoing area of discussion and research. That's a really fascinating point to make about comparison to blood transfusions, actually. Something actually I'd never thought about. That's really, really interesting. So in terms of this procedure, you know, what experimental success have we had with it? Okay, so where this sort of first really took hold was in this context of this particular gut infection, a condition called C. difficile infection, because strioidis difficile infection,

which is a really nasty gut infection that can make people very severely unwell, can even cause very severe information in their gut, and even kills a number of people every year. And it was in this context that there was sort of a really clear rationale to start using faecal transplant, and the first sort of randomized trial where some people, people were given, you know, active treatment and some people were given just sort of standard of care, just normal antibiotics, was back in 2013. And that's where this field really, really kicked off. And when you do clinical trials, you always have to have an ethics committee who oversee

you're doing the trial right and that people are being treated correctly and monitor outcomes. And in fact, the ethics committee for this trial cancelled the trial in the middle of it, because they said the people being given the fecal transplant are doing so much better than people just being given the alternative standard care therapy. It wouldn't be ethical to continue. continue and complete the trial. So since then there's been a huge number of sort of, you know, random, what we call randomised trials where people have been given fecal transplant or, you know, standard of the care just antibiotics for cdifacil. And consistently, with all the data together, we can see that the fecal transplant is a really clinically effective and cost-effective treatment

for this condition. And in fact, Nice, who are the sort of regulatory body in the UK, who look at clinical and cost-effectiveness of sort of medical interventions, recently within the past month or so have sort of rubber stamp this, have published a recommendation on this, which hopefully will mean it gets sort of wider spread uptake. But there's another extension of that, which is, as our research has expanded,

we've started to realise there's a much wider number of conditions in which there might be disturbance or abnormalities of the gut microbiome. A lot of those conditions are related to the gut, so they're common conditions like inflammatory bowel disease or irritable bowel syndrome, a range of different liver conditions, including fatty liver disease, cirrhosis.

But perhaps interestingly, a lot of these conditions are things not directly related to the gut. So they've included conditions like autism. They've included conditions like Parkinson's disease. They've included conditions like obesity. So things where you might not instantly think, hang on, what the guts and the bugs in your gut might be contributory to that. And so based on the success of fecal microveter transplant for C. diffacil infection, and its establishment as sort of part of more routine clinical care,

people have then started to say, look, what's the sort of scope or potential for Fika microboater transplant to be, have it either as a treatment for a range of different conditions, or perhaps to even see it as some sort of exploratory tool whereby if we give it to patients and we change the gut microbiome and some aspects of their health get better, can it give us a bit more insight into how important the gut microbiota is to these different conditions.

So essentially, this is a nascent science that could have all sorts of ramifications in the future. Yeah, I mean, people often make the description of the gut microbiome being a new organ. And if you think of, say, all the organs you think of the body and the range of effects they have in their health and how research they are and how we have specialists who look after just these organs,

be that your liver or your kidney or your lungs. and years of training that doctors, nurses or other specialists might do to become experts looking after that. And essentially, we feel to a certain extent that we've discovered a new organ that's been in plain sight the whole time, but that we're only just recognizing it, and that we're only just kind of really at an early stage of getting to grips with its potential. And the other really exciting thing about it is that the fact that we might be able to manipulate it, that we've got tools like fecal micrototor transplant where we can actually try and change elements of it. And there are a whole range of different sort of ideas about some more refined techniques

where we might be able to use sort of precision medicine tools to either knock out very specific bacteria or knock out particular proteins or chemicals they make or to try and just introduce those into the guts. And so, yeah, it feels to a certain extent for those of us in the field that, you know, maybe we are on the edge of a whole new, you know, generation of discovery here. Yeah. So that's really interesting, but I just want to reverse a little bit when you said about antibiotics. So what is the issue with us taking antibiotics? What effect does that have in a microbiome?

Okay, so the most important thing to say is when doctors are giving antibiotics, they're not generally giving them lightly. You know, they are giving them because they think the benefits are going to far outweigh the risk. You know, so for instance, if people have a chest infection or a bladder infection or men in you know, they are, these are life-saving, these are life-saving treatments and there shouldn't be people who are saying, well, I, you know, I'm not sure about them. They're definitely life-saving treatments. However, we've got to recognise there are some issues that are with us and emerging related to antibiotics. And one aspect is the collateral damage that can

potentially occur related to antibiotic use and particularly that while they're really good for getting rid of bacteria and the causes harm, the collateral damage is that they can also destroy or profoundly disturbed the sort of balance of bacteria we've got in our microbiota. So they can disturb these microboaters that, you know, in our gut or our lung or beyond, that are, you know, play a number of different roles in our health. And to the extent to which those sort of, you know, and as we're in a sort of, you know, this idea is sort of arisen that in a sort of western, westernization of our lives, whereby antibiotic use is sort of more prevalent, and that might mean more and more,

more of a hit to our microbiota, or we kind of, as time goes on, might we lose particular species that we need or the particular bacterial functions we need over time? They're absolutely key in that we're only going to really recognise those when those have gone. There've been some of sort of, there have been a number of people who have made the observation that, you know, the westernisation of our lives has been associated with a big drop-off of a range of infectious diseases, particularly childhood infectious diseases, which is really great. But it's also been associated with a sort of profound explosion of a number of different chronic diseases over time, including asthma and inflammatory bowel disease, etc. And whether that could be related

to disturbance of our gut microbiota through antibiotics or other aspects of westernisation of our lives or changes to our environmental exposure is a sort of keen area of debate. The other, another sort of important area of concern regarding antibiotics that's been really well publicised is the rise in antibiotic resistance. So as we start to put the bacteria in our, in our different organ systems under pressure, you know, by exposing them to a lot of antibiotics, then the bugs start to get smart and we'll, and we'll try and we'll try and they have a number of different escape strategies from antibiotics where they've got particular genes that they can turn on and different range of strategies in which they can escape the effect of antibiotics. And what we're starting to see all

across the world is a real explosion in antibiotic resistance genes and antibiotic resistance infections. In other words, these are bacteria that can cause infections where we've got a more limited armory of antibiotics to treat them than we originally had. So antibiotics are key, they're life-safing, they're really important drugs, but we kind of need to be aware of what are the downstream effects on our gut microbiota or microboater elsewhere, and could that affect our health more broadly? and if we don't use antibiotics more responsibly, what are the potential implications for the future as antibiotic resistance infections grow?

So one thing you said there, like some particular microbes, could I say, and can be lost? I mean, are they lost and just gone forever, or can we get them back? Yep, so this is a sort of area of debate. I mean, I think the thing that we recognize,

just to take antibiotic resistance, you take antibiotic resistance as a, as an example. If we start to use antibiotics more responsibly or we put more stewardship in healthcare settings like hospitals for using antibiotics responsibly, we can start to see over time that those antibiotic resistance mechanisms start to sort of fade out and go away a little bit. And the same might be true of other ways that we're pressurizing our gut for our Western lifestyle. So if we start to do all the things that support our natural environments, you know, And those are things like thinking about antibiotic use, diet, lifestyle, aspects of industrialisation, environmental exposures.

If we start to consider all those sort of aspects as well, then we might be repaid for those sort of considerations by a sort of hanging on to the sort of diversity, mixture, richness of I've got microbiota. We're still at a sort of early stage of recognising this and we don't fully know the extent of it. But I think there's certainly concern enough that says we've got just as we think of, you know, environmental aspects and the degree of responsibility that we have to look after to nature and ecosystems. This is another ecosystem that needs a bit of nurturing as well. Yeah, that's another amazing point. So what's the current situation like with the regulation, like how close are these to being

clinical treatments? Okay. So it's really important to say that, you know, as we've sort of touched on already, because this is a sort of treatment where there's not a huge amount of precedent, where in a way it's sort of like a transplant, like we sort of alluded to in some ways, but in other ways it's kind of like a drug because we think we're starting to tease out some of the mechanisms, how it actually impacts upon the people. And it's been really difficult for regulators to kind of say, what box does this fit into? And that's made it really difficult. So in some healthcare settings, this is kind of regulated like a transcom is. In the UK, for instance, the MHRA, who are the sort of healthcare and drug regulatory body, view this as a medicinal product. They view the regulation more like a drug, but it's different in different settings. And then the other way I'd answer that is by saying that we talked before about a number of people who are going on to look at next generation products. And this year, as I think I mentioned, one product, which is a sort of spore-based treatment

that's in a capsule, that had a very successful troll, and there's an application to the FDA, the Food and Drug Administration in America, who are the regulatory body for drugs there, they're evaluating that. And then over the past week or so, there's been used from America of another product that is a sort of liquid, slurry-based product that's normally given into the bottom end as an enema that is produced by a particular company, which has been had all its trial results reviewed by the FDA in America and has been recommended for licences. seen. In other words, recommended for use as a medicinal product that doctors could prescribe just like any other medical products.

That's really a lot to chew on that. I think by way of closing, I'd like to know, what can we do to look after our own gut microbiomes? I think a lot of the aspects that we recognise are good for our health and recommend for the environmental health are all things that are really important for us. We recognize the key effect of diet and aspects of our lifestyle on our gut microbiome. And there have been a huge amount of work that's been published over the past few years about how just as we know that our diet is so important for our health more generally, that part of the benefit of having a good diet, diets rich in fruits and vegetables, diet rich in pre-bartis like fibre, is their ability

to turbocharge your gut microbiome at the same time and keep it as healthy and diverse as possible. Some of those aspects are things that we've already mentioned already, such as being aware of things that can insult and can impact upon the gut microbiome. So, for instance, we all know that antibiotics are important. Antibiotics are key life-saving drugs, but we need to be really astute eye, and that's particularly people like me as healthcare professionals, about are we giving people the right antibiotics, how long do people need to be on antibiotics? They definitely need to be on them.

And that's not just antibiotics, it's a range of other medications that we need to know can also impact upon the gut microbiome. And that's not the full story, but I think those sort of aspects are sort of key aspects, key starts to try and, you know, raise awareness and try and set the agenda for looking after a gut microbiome. Thank you for listening to this episode of Instant Genius. That was microbiologist Dr. Benjamin Walsh. The current issue of BBC Science Focus magazine is out now.

Pick up a copy wherever you buy your favourite magazines or visit sciencefocus.com. This podcast is sponsored by Name, Audio and Focal. The texture and emotional depth of music can be lost through digital sources or poor signal. Name Audio believes you can have digital precision with analog warmth. Alongside French acoustic specialist focal, Name creates high-end audio systems combining innovation with craftsmanship, so you can listen to music, just as the artist intended. Discover more at Name Audio.

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