Ruairi Robertsons Biomes Podcast Season 2 Episode with Brett Finlay

Biomes Podcast Show Notes: Season 2 Ep 6 with Dr. Brett Finlay

Microbiome Insights is proud to be the sponsor of season 2 of Ruairi Robertson's Biomes Podcast. 

In this episode Ruairi talks with Dr. Brett Finlay, a professor at the University of British Columbia and a co-founder of Microbiome Insights. Here are the key takeaways from the conversation:

  • Dr. Finlay's career background, his journey into microbiome research and microbiome's role in childhood asthma.
  • The interactions between the host, the pathogen and the microbiome ("the unholy trinity").
  • How the commensal microbiome trains our immune system in early life and affects our susceptibility to infections.
  • Antibiotics - their undebatable benefits in tackling infections and caveats associated with their overuse. The detrimental impact antibiotics have on the children's microbiome. 
  • The gradual loss of microbial diversity in our society. How does COVID-19 further contribute to it? What does the rise of non-communicable diseases have to do with it?
  • Future potential of commercially-available microbiome-altering products (ex. Live Biotherapeutic Products).

 

Links to Apple, Spotify, and Podbean

 

Full Transcript 

Ruairi Robertson:

Hello and welcome back to the final episode of this season of Biomes. My name is Dr. Ruairi Robertson and I have the pleasure of speaking with the leading human microbiome researchers in the world to learn what is going on in their labs and in their minds and bring all of that exciting research to your ears and to your guts through this podcast Biomes. We've had some fascinating discussions so far in this season about the microbiomes within us and around us from fermented foods, to cancer microbiomes, to gut fungi and to microbes in the International Space Station with some of the leading experts in microbiome research and this final episode of the season is no different. This week I speak with Professor Brett Finlay of the University of British Columbia. Professor Finlay is originally an expert in intestinal infections and is one of the pioneers of gut microbiome research and its role in childhood asthma amongst various other diseases.

Ruairi Robertson:

I speak with him about the influence of the gut microbiome on our immune responses to infection and how this interaction may influence our susceptibility to immune-mediated disorders and infections including the potential influence for COVID. Professor Finlay along with Dr. Bill Mohn is also one of the scientific co-founders of Microbiome Insights, whom sponsor this season of Biomes and provide end-to-end microbiome sequencing and bioinformatics services. Between the two of them, they have published more than 600 peer-reviewed papers and they provide key scientific guidance to the Microbiome Insights team. As always, Microbiome Insights is providing free study consultations to all Biomes listeners. So to find out more go to www.microbiomeinsights.com and get in touch with the team to tell them that you are listening to the podcast.

Ruairi Robertson:

Brett, thanks very much for agreeing to have a chat. It's great to talk to you about your work in the microbiome field and all of your work kind of over the last few decades I suppose, but can you maybe start off... Tell us a little bit about your background because you started off in biochemistry and then your years as an infection biologist and then you since moved into more commensal microbiomes and how they impact health. So give us a little career background and how you got to where you are right now.

Brett Finlay:

Well, you're right. I did my degrees in biochemistry, ironically never even took a microbiology course, but when I was in graduate school I ended up working on microbes, the pili in conjugated bacteria and just fell in love with the whole concept of microbiology and things. So then I did a post-doc at Stanford, went to a person's lab named Stanley Falkow who is the godfather of the microbial pathogenesis field and he studied how bacteria caused disease. This is right at the beginning of the whole recombinant DNA revolution where we could finally clone genes and sequence genes and things that we couldn't do before, pulling us further away from biochemistry. And then I came back to Vancouver where I've been there ever since and the vast majority of my career has been spent studying how bacteria cause disease. This is mainly pathogenic E. Coli and salmonella and how they actually manipulate the host cells and inject funky molecules in that rearrange the immune system and everything else and reprogram these cells.

Brett Finlay:

And then the way that microbiome came onto the horizon is that around, I guess, over a decade ago now. We were at a lab retreat and one of the things at lab retreat is, we have drinking and brainstorming sessions and we had one of these and someone says, "What about all those other microbes that are in the gut?" This is long before, it was called normal flora back then. And really we all sort of knew there were all these microbes there but no one had any clue what they did, if anything. And this is just in the days when you could then start to use degenerate PCR primers and clone 16S sequences one at a time and you could sequence 20 or 30 of these things, get a snapshot and the microbes that might be there. So we sobered up, came back from retreat and we wanted to have a look at what happens to microbes during diarrhea because we were studying diarrhea.

Brett Finlay:

We started to do that and of course they changed, which was quite interesting. And then one of the people in my lab did a really interesting experiment, Ben Willing, where he basically said, "We knew there was these mice that were resistant to infections and others that were susceptible to infections." Again, this is pre fecal transfers, but he did a fecal transfer, what we now know as a fecal transfer, he put the feces from these resistant mice into susceptible mice and they became more resistant, just by doing a fecal transfer. And of course it works the other way too, you can make them more sick with susceptible animal feces. That plus the other experiment, we realized that we worked on salmonella typhimurium because this causes a typhoid like fever in mice. When you and I swallow salmonella typhimurium, we get diarrhea, gastroenteritis, a completely different disease.

Brett Finlay:

And so we and others found that if you pretreated mice with antibiotics, especially streptomycin, instead of getting a typhoid like systemic disease in these mice, you got diarrhea or gastroenteritis. Just by an antibiotic change, you completely changed the outcome of the disease. And it was those two things that really made me sit up and realize these microbes are doing something there. And so that's when we really started to get into the world of microbiomes, they said it was called normal flora back then, 2005, 2006. And we published a paper showing that, the microbes change during infection and they affect infections and then we're off to the races and I was quite interested in this. And then the next big turn in the lab came when my wife was a pediatrician, we were sitting around dinner one night and I was telling all these cool things, what changed in the microbiota with antibiotics and you could change diarrhea.

Brett Finlay:

And she sort of said, just out of nowhere, said, "Brett, kids that get antibiotics in the first year of life have higher rates of asthma." I'm thinking asthma, that lung inflammation, what could that possibly have to do with antibiotics in the gut? And so then I went back to the library and as every guy knows, wives are always right, even though I didn't believe her at the time. There was lots of papers sort of with smoking guns about microbes might be involved in asthma, but there's no one had done any experiments in microbes and asthma. And so I convinced the young graduate student, Shannon Russell to say, "Well, there's a mouse asthma model next door, why don't we just try treating these mice with antibiotics and see if that changes their asthma" and low behold, it drastically changed them. And that got us into the whole world of early life microbes and asthma.

Brett Finlay:

And that really opened the flood gates to many, many different things. And you know we've been involved into malnutrition and microbes. We have fascinating stuff about gut-brain axis and Parkinson's and all these other things now. And it also drove me to write a couple of books on this subject because it was such a fascinating area. And I now say that if you take the top 10 reasons why you're going to die, 9 of those 10 have microbes involved in it and only one is obviously microbes and that's pneumonia and influenza. So it's been an amazing run in terms of how these microbes... And it's really put microbiology back to the forefront of life. Ironically, I can't get anyone in the lab to work on pathogenesis anymore, they all want to do microbiota and all into gut-brain axis, so that's the really exciting one for everyone. So yeah, it's been a wonderful career trajectory and I've been very fortunate to benefit from it.

Ruairi Robertson:

Sounds like you're doing a bit of everything. But if you can go back to the original account of your start of your career, when you're talking about pathology of infections and how we have become sick from an invading pathogen. I suppose, there's a three-way link between the host-the human, the pathogen itself and also that there's this microbiome link as well. So you did a lot of work on how the pathogens affect the host or infect the host, but what role do those other microbes play in infection? Or how do other commensal microbes either prevent or enhance an infection from causing disease in a human?

Brett Finlay:

Yeah, I mean the role of the host, the pathogen and the microbiome, I call it the unholy trinity, how the three work together. You're right, all three play a role. Defining mechanisms has been slow. Initially, everyone said, they called it competitive exclusion. It's just, if the microbes were already crowded in the gut, pathogen can't come in and can't establish a hold, you take an antibody to clear out the competition, now pathogen can come in. And that does hold true for some things, but we're now learning the mechanisms are much more sophisticated than that. And there's actually germ warfare going on between microbes and the gut, they're trying to kill each other off with type six secretion systems and things. They're sensing everyone, they're cross feeding each other. We just have a paper coming out now, where two microbes, one makes one thing and another one uses, which then feeds the other one back again something else and they're cross feeding each other.

Brett Finlay:

So it's a very sophisticated community interaction and I think you hit the nail on the head unraveling the details, we haven't got them all yet. Before, when we had one pathogen where you could take the microbe and put it in cell culture where they're just human cells and look at that. Now, when you're adding a trillion other microbes to confuse the picture, it is very confusing. So we don't really have all the good answers yet, but I think we're finding that they are very sophisticated, these pathogens queue off of the presence of other microbes to realize they're now in the gut, they're looking for molecules like, "Okay, I'm in the gut now, I'm going to do whatever." So it's a fascinating interaction and so we just don't understand fully yet.

Ruairi Robertson:

I'm sure there's a million pathways that work there. But I suppose if you translate that to humans and human infection, that could be the reason that certain people are more susceptible to infections than other. It might just be that their immune systems themselves are different, but it could be that their commensal microbiomes are different and that what is allowing a pathogen to proliferate, I guess.

Brett Finlay:

Yeah. I mean the analogy I always use is, if a hundred people go to a wedding and they all have the same amount of potato salad, why do 20 get food poisoning and 80 don't or whatever, right. It's not because of a dose. And I think we now realize that is probably a lot to do with the microbiome. Host immune system, to some sense, maybe prior exposure. But I think we traditionally didn't realize the significant role of the microbiome plate. And as you know, every person's microbiome is different and these microbes coming to the gut are each going to experience a different world of microbes depending on the person and so sometimes it works and sometimes it doesn't.

Ruairi Robertson:

Yeah. So in that other link then, between the commensal microbiome and the immune system, how does that work in terms of infection? Because we're learning more now that the commensal microbiome trains subsections of the immune system in early life to help protect against infections later on. So how does that kind of early life microbiome training of the immune system affect our susceptibility to infection later on?

Brett Finlay:

Yeah. I mean, I spent my life bashing immunologists, no offense to immunologists, but I'd say, "lysosome isn't a world killers, why don't you study something useful kind of thing." But I've had to eat my words because immunologists were probably the first under microbiology to embrace microbiome. We worked with some people that were in the early days looking at T-helper cells in the role of microbiome, for example. And what we've come to realize, yes indeed, you're right, the microbes do train the immune system. And we kind of knew that from germ-free mice. Mice with no microbes in them, their immune system developed normally. And then I think the lessons we learned with early life and asthma and how microbes shape Th1 and Th2 type of responses, et cetera.

Brett Finlay:

So again, we don't understand all the ways, there are a few mechanisms that are being defined, short-chain fatty acids and things. But we know that you need these microbes early in life to shape how your immune systems emerge or not. And then we also know later in life, depending on the microbes you have, how your immune system functions and responds and I mean, immune system is sampling microbes all the time. Now, most of those are harmless, but they're also sampling them and so they're aware of them and so they're queuing off of them.

Brett Finlay:

And so, it's ironic you go to immunology meetings now, half of it is microbiome because they realize these things play a real big part and it also helps explain a lot of the puzzles of immunology previously, why some mouse strain behave differently, for example, and even results between different labs. It's of course, because of the microbiome in these particular mice and things. So there's been even suggestions that we should go back and redo all the mouse immunology literature with a mouse with the standardized microbiome kind of thing, because we now realize that they play a huge role and we just had no clue up until a few years ago about this.

Ruairi Robertson:

Yeah. And you mentioned then the influence of antibiotics in this whole unholy trinity or these kinds of interactions. So antibiotics were amazing when they were discovered, they have prolonged lives of people, they've prevented us all dying from infections. But we think that there's probably these side effects in the long-term when they're overused, especially. So maybe you can talk to us a little bit about the evidence behind that for maybe short and long-term effects of overuse of antibiotics on the microbiome.

Brett Finlay:

Yeah. I think you're completely right. I mean, antibiotics were probably the biggest medical breakthrough we had in the last century. I mean, countless lives when they came on about World War Two or something and these were wonder drugs. I mean, infections that normally killed you, you now take a pill, you're just fine. I mean, that was just stunning when they came to life but like all things they were too good and so we used them like crazy. We'd put them into animals to help grow supplements, if you had a viral cold, "Well, let's take an antibacterial agent, it can't hurt, right," and that's been the philosophy and we now know. I mean, I guess my take on antibiotics is that, they still are wonderful drugs. Everyone's aware of the anti-microbial resistance issues of overuse.

Brett Finlay:

But I think what we didn't previously realize is the drastic impact they have on the microbiome. So when you take an antibiotic for particular infection, that antibiotic is not just killing the infectious agent, it's wiping out, its carpet bombing so many other microbes because no antibiotic targets one microbe, they target groups at best and often just everything. So yes, when you take antibiotics, you have a big effect on microbiome. This has an effect on us. One example that I've been personally involved in is in BC, the province we live in, we've had a major quest to decrease antibiotic use in kids, one to two years of age, over the last 10 years, we've done a really good job in decreasing antibiotic use. Pediatricians are very good.

Brett Finlay:

Now, asthma takes about five years to kick in. And if our theory of "the early microbiome is important in asthma" is right, then about five years later, we should see a drop in asthma rates in BC, in kids, they've now reached age five. This is exactly what we see. And so we worked with others around the province and we basically looked at the microbes that were being changed with these antibiotics and yes indeed, these antibiotics are drastically affecting the microbes and you have a much higher chance, the more antibiotic courses you take of having asthma. And we could see the antibiotic damaging the microbes. And basically, based on this, we've dropped asthma rates by 25%, which in BC represents 1200 kids a year that don't get asthma now because they're not getting any antibiotics that destroy the early life microbes.

Brett Finlay:

And antibiotics, we all know that they increased obesity rates for example, anxiety, depression, various brain issues are exacerbated by antibiotic use. So with antibiotics, yes indeed, if you have a life-threatening infection, you take the antibiotics. I mean, don't be crazy, it'll save your life, but also they're not perfectly harmless. And I think between antimicrobial resistance and antimicrobial use, I think that you got to really think about where you use antibiotics. Use them sparingly and as needed. And the area I would like to see much more research in is, microbial repair post antibiotics. So we have taken antibiotic in a young kid, how can we give them back the microbes they need, so they don't go on and get asthma or obesity type thing. And there is really little research in that area right now.

Ruairi Robertson:

And so what would that answer be? That was going to be my question. How do you prevent those negative effects? I mean, there's been some interesting data to show or at least some kind of people hypothesizing that if you take a stool sample maybe prior to antibiotics and freeze it and then take your antibiotic course and you can reconstitute yourself with a self fecal transplant. Do you see that being a realistic treatment in the future? Is the effect of one course of antibiotics bad enough that kids should be doing that or adults should be doing that? How do you see these things playing out?

Brett Finlay:

That's pretty drastic, thanking your poo in your own freezer. When you take an antibiotic, your microbes do get hit, but then they kind of come back to just about where they were. If you take another course of antibiotics, they go further away, but they don't come quite back so close and another course of antibiotics, they go down here. So basically, the more course of antibiotics, the further from normal you become. So one course doesn't affect them too much. Where you do see the big effects is in the young kids. And so we've been working on, can we test which microbes the kids have? And if they're missing these certain key microbes, could we add them back? Almost a probiotic concept or if they took antibiotic, could you add them back?

Brett Finlay:

This is certainly not commercial yet. So in the meantime, I think one needs to think about if it's your kid, supposing that the dog's went to play outside, all the other ways that you acquire your microbes back again, healthy diet type things, try and encourage them back. But generally speaking in older people, not young kids, one course is not too harmful, repeated courses certainly are. In young kids, one is harmful and I think we have to rethink that and ideally come with ways of testing a kid, post antibiotics or you're missing these things and we can give them back some and I think that will be in the future. Same as when a kid is born, they'll get their genome sequenced, so they'll also get their microbiome sequenced and they'll think, "Oh, you're missing these things, we should think about replenishing these some way."

Ruairi Robertson:

You've talked about that clearly a lot in your book, Let Them Eat Dirt, which is taking a lot of the evidence from these really fascinating studies showing that kids that grow up on farms or grow up with pets or grow up in bigger households are less likely to have these longer-term illnesses like asthma, like allergies. So what is happening there? And what is the mechanism behind that? What do we know apart from these observational studies in these children? Or why is that happening? That these kids are more protected if they grow up in a farm or grow up with a dog, for example.

Brett Finlay:

Yeah, you're right. All those things add about a 25% increase, if you had a C-section or if you don't live on a farm or if you don't breastfeed or if you take antibiotics to your asthma rates and about a 30% chance your obesity rates. So the question, what are they doing? And what I think most science is pointing to is that, as you develop earlier in life, a normal delivery is a vaginal birth, which is gross as heck, but it's also the best present a mother ever gives her kid because they boost vaginal and fecal microbes. We're designed as organisms to experience that and that's when you get the first microbes that are involved in breaking down breast milk and things like this. And so C-section you miss that and so you don't get the same microbes, you get more like skin microbes from your mother and things in those microbes.

Brett Finlay:

And the immune system is just programmed to cue off, this is a normal event. And when that normal event doesn't happen, we know the immune system skews more towards an allergic type response. So, that then affects how you then respond to asthma later in life. With respect to obesity and things, again, these microbes are different and we know that you can do fecal transfers from obese animals into thin animals and transfer the phenotype obesity. So these kids again, have this birth microbial scar where the microbes aren't what they normally should be and so they're not the same. And I think a lot of this goes back to this whole society for the last 125 years, has been on a war against microbes. So that sanitation, hygiene, antibiotics, vaccines, and this has done wonders for infectious diseases. I mean, it's gone like this in most developed countries.

Brett Finlay:

But what's going on the other way? Asthma, obesity, diabetes, ADHD autism, IBD, and they're all going crazy. And the question is, well, what's that about? And we really think now that in our quest to get rid of microbes that cause disease, we're also getting rid of other microbes and we're getting less and less diverse in our microbes and we're all living in cities. So think about this, think about single mother has a kid, she lives on the 25th floor of a condo somewhere and she has to have a C-section medically because some women do, she gets mastitis, can't breastfeed. The daycare is next door, pets aren't allowed in the building, their playground is on the concrete roof. Now, picture a kid living 300 years ago. I mean, they're covered in feces, they're out there playing all the time. Yes, there's infectious disease and there's a good chance they will die of an infection, but those that don't have a very different microbial exposure than the one we get today.

Brett Finlay:

And I think our biggest concern is that, each generation we get cleaner and cleaner. We get less than the microbes we actually evolved with. And we're taking a key piece of our evolution out of this equation by living the way we do in our big cities with sanitized everything and don't get dirty type thing. And I think we're also doing an amazing experiment right now, which has COVID and people are not contacting anyone else, they're staying inside, they're eating different food than they did. And so there's all the micro labs around the world are ramped up to see what is this huge experiment of humanity doing to our microbes and everything we know it's not good because we basically living more clean and we all know that is not a good way to do it in terms of microbial exposure. So I'm guessing we're going to see some long-term COVID damage, people don't travel anymore. And so we're not swapping the microbes as we used to. So I think we'll see some interesting things come out of that too.

Ruairi Robertson:

Well, that was going to be my next question is, we know that these clear links between microbial exposure and early life and some of these chronic illnesses like asthma and IBD and these other ones that you've mentioned, but what do we know about infection now, we're in the middle of a pandemic, it's likely going to happen in the future. Do we know how susceptible we are to infections later in life based on our microbial exposure in early life? Or is that too soon to tell?

Brett Finlay:

With respect to the COVID, it's too soon to tell. There are studies coming out showing that people with COVID have different microbes than people that didn't get COVID type thing. There's not a lot of GI involvement, so I'm not quite sure how that's working. I guess, the data is just too early in that sense. But I think getting back, it's not just early in life you want to look after your microbiome. I mean, the other book I wrote on the whole body microbiome is all about aging and healthy microbes as you get older. And a lot of that is dependent on how you spent your life and setting up for the aging process and all that you do during life to basically have a good microbiome as you start to age.

Brett Finlay:

And so, I do worry about what COVID is going to do to everyone's microbiome. We're going to suddenly realize, "Oh, that was not good for us. We've suddenly gone into isolation and not getting new microbes all the time, we'll see." People that are locked down in the elder care places, they're not getting any microbes, how's that going to affect them type thing, so we'll see.

Ruairi Robertson:

We'll see what happens. And well, as you mentioned, there's this interesting exchange of microbes between people, we're learning more about that now, that we are kind of exchanging microbes with each other and you have proposed that some of these noncommunicable diseases might actually be communicable in a sense because of our shared microbiomes and that transferring microbes between each other may actually transfer risk of some of these diseases. Maybe you can tell us a little bit about that and how that might be happening.

Brett Finlay:

Yeah. Last year I published that, it's very provocative. So by definition, communicable diseases, those are infectious diseases, those are both bacterial and viral, all the ones we know and non-communicable, by definition, are diseases that you don't get through microbes. So this is obesity, diabetes and Alzheimer's and dementia and all the ones, that we think is non-microbe. But as I've hinted at, they're now more and more becoming a microbial involvement and people with these non-communicable diseases, their microbes are dysbiotic. They're not normal, they're different than people that don't have those diseases, but that doesn't say that's causing the disease. But it's hinting that maybe there are microbes in there. We've also learned for many of these diseases, like obesity, diabetes, inflammatory bowel disease, autism, you can transfer the phenotype of that disease through the feces, just by doing fecal transfers.

Brett Finlay:

We know this in animal models, we can take the feces from a diseased person, normal person, put it in animals and trigger that disease, you're not, even in Parkinson's you can do these kinds of things. And so that implies you can actually transfer the microbes and this phenotype causing the disease. And so the other thing is that when you look at disease incidents, for example, if you have an obese friend, you have a 40% higher chance of becoming obese yourself, the rates of inflammatory bowel disease of spouses with IBD. So that genetic related are much higher than they should be just on a normal population base, for example. People living in India have very low rates of inflammatory bowel disease. They moved to North America, they now have the highest rate of IBD based on the ethnicity of any group you look at, what changed? They didn't genetically change when they moved to North America or the UK.

Brett Finlay:

So there's all these smoking guns that maybe you could transfer it. So to try and prove that I use something that going back to my roots in infectious diseases, it's called Koch's postulates. So Robert Koch was a very famous microbiologist that showed that many diseases are caused by microbes. And to do that, he set up a set of rules, he called them Koch's postulates. So the first rule is, if a microbe is causing that disease, you have to be able to isolate it out of the diseased person and not out of the normal people. So let's call dysbiotic microbiota, the pathogen for this case. So yes, we can isolate these things out of them, we can grow them because you grow this pathogen and then in Koch's postulate you then put the pathogen in this normal mice and cause disease.

Brett Finlay:

We do that when you take the dysbiotic microbiome from IBD or Parkinson's or whatever, put it in animal, you cause disease. And the final part is you then have to re-isolate that pathogen out of it. And of course we can re-isolate dysbiotic microbiome. So in a sense, this basically proves that some of these non-communicable diseases are caused by these dysbiotic microbiomes. The implications are very profound and how we think about things because when you're thinking about the obesity epidemic that's occurring worldwide, we're not really thinking about microbes and microbes transfer. Another really interesting example is, they did a big study on 2000 American military people who were stationed for two years in the high or low BMI type environments. And they did a bunch of controls and of course their weight went the way you would expect it to go, if this theory is right.

Brett Finlay:

Now, there might be other confounding factors, but they tried to sort out what people were reading and things. So I think it's just another way of looking at these things. And when we're thinking about these non-communicable diseases, things like cardiovascular disease, you gotta wonder, are these, the sharing between spouses of these microbes, actually contributing to disease or are these ways of potentially preventing diseases, decreasing them by watching what microbes get exposed to. So time will tell if it's true, but it's a really heretical concept and I've certainly got a lot of interest. Well, let's put it that way.

Ruairi Robertson:

Testing the waters. So how much does that actually happen? Say within a household or within your close friends. What types of microbes do you share? How many of your microbes to share? Or how susceptible is your microbiome to change from your close contacts, I suppose?

Brett Finlay:

Yeah, that's how you transmit it, I think that's the biggest reason that we've really not found any human genetic factors that say, "You're going to have this microbe type thing." Of course, there's some immune things, but for most part, it's all who you're contacting with. If you have an identical sibling lives on the other side of the world, your microbiome is going to be much closer to the person you're living with than that identical sibling, somewhere else in the world, it's all environment. When you kiss someone, you transfer 80 million microbes.

Brett Finlay:

And there was a really neat study, they looked at a little Island in the South Pacific. They figured out who is married to who, just looking at their microbiomes, just because they were similar you could tell who was living with... I don't think they included one night stands, but you can sort of figure out who you're spending your time with just by the microbial composition. So yes, household transmission is huge. Now, also you live in the same house, you're eating the same things, so that comes in, you're sharing the pets, et cetera. So yeah, it's all environmental, genetics play virtually no role in which microbes you have and don't have.

Ruairi Robertson:

So what I'm interested in is what kind of a future this is because of this field is because at the moment it's all very descriptive. We know what microbes live here and there, there's these associations between all these diseases, but what do you see the future, first off, in terms of treatments or therapies. How do we kind of restore this diversity that we've lost? Or what are the realistic outcomes that we can expect if we really want to reverse this trend?

Brett Finlay:

Yeah, I think there's medical and then there's sort of just the rest of the world. I mean first off, each person thinking how they live, incorporating microbes into a diet, exercise, all these things is a major way of altering these things. But medically, I think we're going to see, really quite frankly, a revolution in how you actually treat some of these diseases. And we see in the efficacy of fecal transfers in C.difficile, for example, you get 90% plus cure rates doing a fecal transfer. I think as the great proof of concept, I don't think fecal transfers will be a mainstay of medicine, they're rapidly moving beyond this, where you'd have 8 or 10 or 12 microbes growing up in a lab as a mixture, take that pill into a person, unlike probiotics, they're from the gut, they're for the gut.

Brett Finlay:

I think probiotics, it's gotten a rather bad name because they're introducing idea, but they're not doing it right. They're not taking microbes from the gut and mix communities and putting them back in. So I think we'll see a whole new generation of microbial mixtures. They call them Live Biotherapeutic Products. You can actually take to treat certain things and there's companies, and while the few of them, they're actually moving this along quite nicely, they're in phase three trials now of doing this and they're going to be a medicine through the FDA type licensing and proving they have medically work and we will see this. Then I think the next generation after that is what you hinted at earlier in our discussions is, what are they actually doing? And when you think of how microbes interface with us, it's not the microbes that do it, it's molecules they make.

Brett Finlay:

So I think this whole quest to identify the metabolites or whatever these microbes are producing and always seeing short-chain fatty acids is one example, but I think there's many molecules that can be mined. And once we start to figure those out, then that's easy because then they're just drugs and we know how to develop drugs really well. And we will get these microbial molecule drugs that I think will then be used in medicine to do these things and this will be... Let me just give me one example, cardiovascular disease, atherosclerosis. We know that the microbes play a key role in breaking down basically red meat. And if you don't eat microbes, you don't get atherosclerosis, heart attacks and strokes type thing. And we know in mice, if you drug those microbial pathways that cause this first breakdown, you can feed the mice all the red meat they want and they will never ever get cardiovascular disease.

Brett Finlay:

So I could see how that could come quite quickly, where you drug the bugs. So then you go and have your steak that night kind of thing. You just shut down that pathway and then they can't break it down, so you basically don't get cardiovascular disease. So I think it's going to really change how we think about things. Others examples is brain disease and MIND diet, which is basically Mediterranean diet. You follow a MIND diet, you have about a 50% less chance of getting Alzheimer's and we'll have a paper that's about to come out now on Parkinson's. And if you follow this diet basically you can delay Parkinson's onset in women by over 17 years, in men by at least six years, just by following this diet. Now, there is no other treatment or prevention in Parkinson's. It's not traditional medicine, but I think it's very profound in the ability to control disease. And I think it's become much more mainstay as we figure it all out.

Ruairi Robertson:

That's amazing. And how much, aside from kind of actual treatments and/or diets and everything, but how much will technology play in this? Because the whole reason the field of the microbiome has flourished in the last few years is because of these massive developments in sequencing technologies. Where do you see that developing? Will there be kind of at-home self-testing of your own gut microbiome, your own metabolome or how will that advance in the next few years in order to create those kinds of personalized approaches to your own gut?

Brett Finlay:

Yeah, I think that's a really good point. I mean, it's due to sequencing, we now sort of start to begin to understand the microbiome because before you couldn't grow it. If you streak your feces out, very few will grow. So by sequencing, we don't have to grow them, that's where the whole mainstay is been. I see microbial sequencing much like genome sequencing, the whole personalized medicine concept and that you'll have your genome sequenced, I also think you can get your microbiome sequenced. When you're trying to look for susceptibility diseases markers and things. I mean, I speak at several personalized medicine type conferences and they're all talking about these GY studies in human genomes. I say, "Look guys, you're barking up the wrong tree. Only 1% of the DNA in and on a homo sapiens is homo sapiens, the other 99% of that DNA is microbial. Why are you working at less than 1% of the genes that are in this person?"

Brett Finlay:

They, of course, don't like to hear this, but I think, when you look at adverse drug reactions, they've been very poor at tracking down human genes that give adverse drug reactions. That's because when you take a drug, who breaks it down? The microbes, who forms the adverse secondary metabolites concerts reactions? The microbes do. So. I think they're just plain wrong in terms of what they're looking at, they're missing the obvious that these microbes play a central part in us and this whole field of personalized medicine, if you and I are 99.99% genetically identical at a homo sapiens level, our microbes are clearly different. So where are the differences between you and I? It's not our genes, it's the microbial genes that make us different.

Brett Finlay:

And so I think we need to really embrace that in the whole personalized medicine. As for a home kit that immediately sequences it, maybe, I'm not sure we even need to do this. As we figured out what microbes are doing, we can look for a few particular ones that might be at risk for a certain thing. You can test for that pretty easily, I would think. But I would think that getting a microbiome test will be as routine as getting a throat swab or strep throat for example, in the future because sequencing needs to be so cheap, you just take a fecal swab, a throat swab and even in analyzing what infections you have, it's easier just to sequence all, just do a throat swab and sequencing it rather than do a strep throat transfer for example. So I think we'll see that come online as the sequencing gets so much cheaper in the future.

Ruairi Robertson:

And say that, does happen. Say we are able to sequence our microbiome really quickly. We find that it is at a certain state, how easy is it to make those long-term changes to a microbiome, especially a gut microbiome because we know that if you live the same lifestyle with generally the same diet and the same exercise regime and the same people around you that you've spoken about, your microbiome tends to remain pretty stable until you get older and it will kind of drop off. So say we do reach that kind of future, how easy is it going to be to change long-term?

Brett Finlay:

Yeah, I think you hit the nail on the head. In fact just already pretty easy to get your microbiome sequenced, it's not overnight, but you can get it done pretty quickly and a good idea. So then the question is, well, what do you do with that information? That's the hard part. And you're right, it is a pretty stable ecosystem and basically you have to think about it as you're trying to disrupt an ecosystem. And so that's why when you take a lactobacillus from vagina or bifidobacterium and you swallow it at 10 billion a day or whatever. It doesn't stick, probiotics don't stick. They're not built for that environment. So you have to think, well, how do I make the environment more susceptible to receiving these microbes and we already know a diet is a major part of it. You can change diet and you will change your microbes quite quickly.

Brett Finlay:

We've learned that adding live microbes to people often, ironically, pretreatment with an antibiotic, which clears up the competition, allows these new better ones to stay and say, inflammatory bowel disease when your guts are on fire, you not only add antibiotics, you also add anti-inflammatory, so tone the inflammation down, so these new guys can get a hold to start producing the anti-inflammatories. They need to then establish it. And then also I think you need to come in with communities, you can't just come in with a single microbe. You need to come in with mixtures of communities and they're built for the place you want them to go, they're from there and they're just going back there and they know how to grow there and so we'll see that. But, I think that's probably one of the biggest challenges right now is, how do we correct a microbiome once we figure out it is wrong. And yeah, we're playing with those answers, I don't think we have the definitive ones yet.

Ruairi Robertson:

We'll see what happens, I guess.

Brett Finlay:

It is an experiment.

Ruairi Robertson:

Yes, it is an experiment, I suppose. But if we lose them, I've talked in a previous episode to Maria Dominguez Bello and she's doing this fascinating work about preserving our microbes. Like we preserve seeds in a seed vault in case of world extinction because of nuclear war or something. So how easy is it then once we lose these microbes to kind of reintroduce them back into humans, be it in ourselves or at a population level. Once they're gone, are they gone or like kind of species becoming extinct in other ecosystems or can we have hope that they will be re-introduced?

Brett Finlay:

I think that's a really, really scary and important point. I must admit as I worry that my grandkids, the microbes that are available to them are going to be very different than ones that were available to me when I was a kid, for example. And so I think they're very worse, I mean with each generation we know we're getting less and less diverse microbial. That's bad in terms of ecosystems. You need the diversity type things. And I think putting them in vaults and trying to save for future generations... We should do that, but I worry that it's going to be just too late when we suddenly realize, "Oh geez, we've just gotten rid of a key microbe that's been part of the evolution and it's nowhere to be found in the world anymore. We can't do this anymore."

Brett Finlay:

So there's been some studies showing that after about two or three generations, if you don't eat fiber, you lose the fiber producing microbes kind of thing. They go extinct. We don't eat fiber anymore compared to what we used to and how we evolved as a species. And so we're losing those things. So yeah, I'm very concerned about this and I don't know what the best answer is, other than try and make our microbiome that we have. I mean, we're all living long as we ever have, so it's not like humanity is in trouble right now. Humanity is doing great, I mean, too well actually, we're way overpopulating the world. So lifespan is great. So once we've lost a few microbes, we seem to be doing just fine without them.

Brett Finlay:

But I think where we do see this reflected is in the whole increase of non-communicable diseases. When you look around that causes the 70% of the world's diseases and it's due to our imbalance in microbes. And so I think you want to think about, yeah we can live to 80, but I wouldn't mind living a little bit healthy till then. That's when the microbes got to come into the picture. So we have to do anything we can to protect these things, there's only about a hundred microbes that cause disease in people and instead of thinking them as the enemies, they're our friends, they're built to live with us. This is the world we evolved in. Why are we trying to... well, the earth is too polluted, let's help set a station in Mars. I mean, that's just plain stupid.

Brett Finlay:

And that's what I worry about this whole microbial assault thing is... Now, COVID set us back many years because now we're going back to the whole fright of infections and so I worry about that. We're going to release a documentary, Let Them Eat Dirt, telling everyone, "Let your kid get out there and get all these microbes," then COVID hit. Now, we're scared to release it because it sort of goes against what we're experiencing these days. So it's a balance, but I really think we have to think about these microbes as being part of us instead of being the enemy.

Ruairi Robertson:

So, that's it. Season two of biomes is done, finito. And I'd like to thank everyone who is listening. I've personally really enjoyed this season and the fascinating discussions that I've been lucky to have with some of the most brilliant minds in the field. If you've enjoyed it, please rate the podcast on Apple, share it with any of your friends and family, leave a review, send it to anyone who might be interested. And if there is any interest, you never know, there could be a season tree. A special thanks to the sponsors of the second season, Microbiome Insights. They have a great team who provide all the services you need to conduct a microbiome study, whether you're in academia or industry or public health. So head over to their website, microbiomeinsights.com to find out more. Thanks very much from me, stay safe and hopefully I'll be back with some more biomes soon.

About Microbiome Insights

Microbiome Insights, Inc. is a global leader of end-to-end microbiome sequencing and highly comprehensive bioinformatic analysis. Based in Canada, the company’s diversified suite of services enables industry and academic clients to include microbiome analysis in studies across a range of human, animal, agricultural, and environmental applications. Our award-winning team has worked with over 50,371 samples from industry and academic clients and has a reputation for providing friendly, efficient service.