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Video: Canada at the Cutting Edge of Innovation: Humans and the Microbiome

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Presentation and fireside chat with CIFAR fellow Dr. Carolina Tropini about her research on microbiota, gut health and precision medicine.

Duration: 00:57:30
Published: May 25, 2022
Code: TRN5-V23

Event: Canada at the Cutting Edge of Innovation: Humans and the Microbiome


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Canada at the Cutting Edge of Innovation: Humans and the Microbiome

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Transcript: Canada at the Cutting Edge of Innovation: Humans and the Microbiome

[The CSPS logo appears on screen.]

[Marc Fortin appears in a video chat panel.]

Marc Fortin, Natural Sciences and Engineering Research Council of Canada: Hello, everyone. Good morning all, hello to all, welcome to the Canada School of Public Service. My name is Marc Fortin, I am the vice president of research partnership at an organization called NSERC, NCERC stands for the Natural Sciences and Engineering Research Council of Canada. We are the organization that funds every year, about $1.1 billion of scientific research in universities and colleges across the country. We fund 11,000 of the best researchers in Canada, 30,000 students a year, and these are the people who are the inventors and innovators of the future. So, today, I'll be the moderator for the event, and I really want to thank you for joining us today for this event. But before I go any further, I'd like to acknowledge that I am joining you today from Ottawa, situated on the traditional territory of the Anishinaabe people, and we want to recognize their stewardship of the land and hope to be inspired by their knowledge from coast, to coast, to coast.

Today's event is the fourth instalment of the Canada at the Cutting Edge of Innovation series of the Canada School of Public Service, which is delivered in partnership with CIFAR, CIFAR stands for the Canadian Institute for Advanced Research, and the goal of the series is to introduce public servants to leading scientific experts who are focusing their research on key questions that we, Canada, and overall globally, we are facing and continue to face in coming years. Today, it's really fascinating, a really fascinating event on the topic of the human microbiome. Well, the microbiome actually describes the ecosystem of bacteria, fungi, viruses that live inside us. Each one of us has a different microbiome, our microbiota are completely unique to each and every one of us. The microbiome is shaped by our genetics, our environment, and the microbiome is an important determinant of our health.

[Another panel with Dr. Carolina Tropini appears.]

Joining us today is the CIFAR fellow, Dr. Carolina Tropini, who is assistant professor in the School of Biomedical Engineering, Microbiology and Immunology at the University of British Columbia. Carolina, a very warm welcome, thank you so much for joining us.

Thank you so much for taking the time, you're a very busy person and we value your time with us today. I can attest that you're a busy person because most of my career, prior to joining the public service, I was a researcher myself at McGill, so I'm still able to read some of the science publications. And colleagues, the publications of Carolina are just stunning, not just in quantity, but in the quality of the work that she does and who she collaborates with. She works with the best in the world on the topic of the microbiome, so we're very lucky to have you today and really, thank you for making time.

Carolina and her team use a combination of cutting edge experimental and computational techniques to study how physical environments affect the microbiome. Carolina, I can't wait to hear your presentation on humans and the microbiome, but before I turn the platform to you, I just want to bring a few housekeeping items. We of course, want you to have the best experience possible, so we recommend that you disconnect from a VPN, you may want to join from a personal device if possible, and if you are experiencing technical issues, we would recommend that you relaunch the webcast link that was sent to your email. 

Over the next 20 minutes or so, Carolina will be walking us through her presentation, and after that, we will have a fireside chat, a question period with the audience, and each one of you in the audience will be invited to submit questions. You can submit your questions throughout the event in the Collaborate video interface. You'll just go to the top right corner of your screen, click the raise hand button, and enter your question, and we will be monitoring the inbox throughout the event. Simultaneous translation is available for participants joining us on the webcast, you can choose the official language of your choice on the video platform. Without further ado, Carolina, the floor is yours, I can't wait to hear your presentation. Carolina.

Carolina Tropini, University of British Columbia: Thank you so much, Marc, thanks for the lovely introduction. And thanks everyone for coming to this presentation, it's really my pleasure to be here. So, I live, work, and learn, and do research at the University of British Columbia, which is located on the traditional, ancestral, and unceded territory of the Musqueam people, and my lab studies the impact of the gut microbiota on human health. You may wonder about my title, it's talking about industrialization and metamorphosis, and the reason why I'm going to have to be telling you about industrialization is that we can't understand the microbiota without putting it into the context of our broader human ecosystem. Part of the reason why this is the case is that in the lab, we study a number of chronic diseases that are really involved by with a microbiota, and over the years, we've been learning that the root cause of a lot of these so-called modern diseases... So, here, I'm thinking about inflammatory bowel disease, diabetes, allergies, or obesity are really rooted in our changed lifestyle due to industrialization.

And I'm going to start telling you about the importance of our microbes to our health, but I will frame this from the perspective of industrialization. Industrialization has really defined the growth of human communities as we experience them today, and importantly, it has impacted living systems from the micron to the global scales.

[Carolina shares her screen. A slideshow includes illustrative pictures as she speaks.]

Over the years, what I found are really important are the parallels between the microscale world and our global scales, and disconnections are really astounding, and it has very much changed the way that I think about human health. Case and point here, I'm showing two images, one of them, the one on the right, is a microscopic gut section, and the other one is a satellite image of Nunavut. These images span over 12 orders of magnitudes of space.

[They both feature similar swirling wisps.]

And what I'm going to tell you about today is that really, everything that is happening in our environment has a parallel inside us, and generally, that the same forces that affect us as humans are also affecting the ecosystems that are within us. When we think about the macroscale, it's really obvious that the cost of industrialization has been really massive, from the destruction of forests to increased pollution. We are now estimating that about a million out of the 8 million species of animals that are present on Earth are on the risk of extinction. And importantly, the other ones that are not at risk of extinction have really had to adapt. Industrialization has also had a cost to the environment inside us. As Marc mentioned, inside us live tens of trillions of organisms, and to give a sense of how many this is, it's about a hundred times the number of stars in the Milky Way, it's a really incredible number of entities that live inside us and help us through our lives.

The reason why the microbiota is important to us and to our health is because they're a little bit like a personalized pharmacy in our gut. Anything that they produce and that makes it into our intestines will go through our blood system, the same way that when you take a pill by mouth can affect our headache as much as it can affect our allergies. We're heavily changing our gut habitat due to industrialization because we've changed the way that we eat, the way that we fight disease, and also the way that we interact with our own environment and with our human communities. All these factors change the gut habitat, and we're finding that they cause long-term change not only to the micro biotic composition, but also in what these microbes are able to produce, and that in turn, changes the pharmacy in our gut, and that can affect our health, particularly as these changes happen early in development.

And importantly, industrialization has put a really tremendous pressure on these organisms and has led an incredible number of bacterial species to disappear, and throughout the talk, you'll see why this is important. Something else that has come about is these modern diseases that I was telling about very much change the environment themselves and will also affect the microbiota, creating a cycle. We also take a lot of over-the-counter compounds, which affect the gut environment. To give you some examples, for example, if you have a fever, this will change systemically, your body temperature, this very strongly affects the way that bacteria can grow in the gut and how they can reproduce. On the other side, when we take anti-inflammatory drugs, this may change the temperature in ways that are less physiological than what the body wants to respond to.

When we think about anti-acids, we're changing the acidity. And finally, another measure of... Which I guess at the macroscale you would think about as salinity, is the measure or osmolality, or the concentration of the molecules that is present in an environment, this also very strongly affects the gut environment, and this can be changed due to malabsorption, so people that are lactose intolerant, or due to laxatives, or for example, colonoscopy prep, will very strongly change this type of environment in the gut. And we used to think about all these effects as being very acute, so how come can they actually change the environment so strongly? And here, I'm going to zoom back out to the macroscale.

[0A slide shows the earth and the outline of a bear. It reads "Environmental perturbations affect organisms at all scales. Global warming: 1.5-2° C difference. 106 species face extinction.]

With global warming, we're only talking about a couple of degrees of temperature change, and this is leading to the extinction of over a million species, because the warmer temperatures are disrupting the natural equilibrium.

Now, let's turn this back to the gut. Global warming is very much akin to what happens in our body in the presence of a fever. And of course, a fever may only last a couple of days, but what matters is the relative timescale to the growth of these organisms. So, bacteria have a life cycle of tens of minutes, and for them, a day can account for tens of generations, which is very similar to what polar bears are experiencing with global warming. So, the fact that we change the physical environment over timescales of weeks with over-the-counter drugs or with this type of chronic diseases really means that we are changing our gut microbiota in a way that can be permanent. And what we really want to understand is how is this going to be affecting our health?

[A new slide is titled "COVID-19 aside, industrialization has helped eradicate infectious diseases. A graph shows immense decrease in incidences of Rheumatic Fever, Hepatitis A, Tuberculosis, Mumps and Measle from 1950 to 2000.]

So, if I told you that our changed lifestyle through industrialization has impacted our microbes, and this initially has led to really important improvements to human health. Here, I'm thinking about development of vaccines, antibiotics, new drugs, improved hygiene has really allowed this unprecedented reduction in infectious disease, and this has really correlated with the incredible growth of human populations. But this also has come at a cost, because marrying the sharp decline in the incidence of infectious diseases, there's also been an alarming surge in autoimmune and allergic disorders.

[A second graph on the same time scale shows a vast increase in Crohn's disease, Multiple sclerosis, Type one diabetes and Asthma.]

And it was about in the '90s that scientists began to wonder if these two trends were connected with the idea that maybe the reduction of infections were actually affecting the human immune system in a way that it caused it to malfunction, and we're finding out that this is indeed the case.

The reason why this is happening is that the antimicrobial therapies affect more than infectious agents, they also affect the type of commensal bacteria that we... As we'll see, we have evolved with, and that are important to our health.

The question now becomes why would changing this microbiota actually affect our general health? And the wisdom that we know about this comes from a very long time ago, it was even Hippocrates that at 300 BC, said that all diseases begin in the gut. We're very tied to our gut because this is where we're exposed to a lot of the compounds that come from the outside, whether they're from the diet itself, whether it's from exposure to pathogens, or whether it's from the production of molecules from our microbiota. And there's also been in philosophy- for example, Feuerbach saying that "we are what we eat." We've very much been connected to our food and to the way that our gut functions in order to understand our health. 

What we're learning right now is really that the key connection between a lot of the way that for example, different drugs may function in different people are really determined by the way that the microbiota is able to metabolize them, as well as all the other factors that I've told you so far. And we have to start thinking about our microbiota as affecting beyond the gut, it's not just a localized to our intestines, it will be affecting everything that our blood system will be able to reach.

So, so far, I've told you that industrialization has changed our lifestyle, and the next two things that I'm going to be telling you about, a little bit of- to vignette, is going to be about the impact of over the counter drugs on our microbiota, and then I'll tell you a little bit about what our lab has been thinking in terms of trying to restore these ecosystems. I've introduced how we think about the microbiota and how the environment can be changed. So, one of the ways that in which I told you about the environment being changed was that in the measure of osmolality, the number of molecules that are present in the gut... And it is actually one of the modes of functioning of laxatives. So, laxatives are these non-absorbable compounds, particularly osmotic laxatives, for example, MiraLAX or RestoraLAX or magnesium sulphate. These are compounds that our body cannot absorb, and in order to equilibrate the osmotic potential, this causes water to be drawn out of the epithelium and increases the motility.

Also, I apologize because I realize for those of you on the East Coast, this is very close to lunchtime and we will be talking about laxatives for the next few slides, just so you're aware. Laxatives are not only used for colonoscopy preps, but they're also very highly used in the general community. So, in the United States, they're the top two digestive remedy, and this is also true in Canada, very highly used, and one of the things that we're concerned about is they're also very highly used in the pediatric population. We wanted to understand how laxatives impact the gut microbiota, and one of the measures that we think is really important to think about this ecosystem from a broad perspective is looking in situ, looking at what happens at the gut lining and the gut interface with the microbiota.

[A slide reads "Malabsorption and laxatives change the gut environment." And shows a scan image of an untreated gut in three colours: red, representing bacteria, green, representing mucus, and blue, representing the intestinal cells.]

So, here I'm showing a micrograph, this is very similar to what you would see by taking a biopsy, this is an experiment done in an animal model where you see that here on the right-hand side, these are the intestinal cells, so these are what we refer to as the whole cells, when we think about humans, we are the host of this microbiota. These intestinal cells are very tied to the bacteria, to the microbiota that is here, highlighted in red. These bacteria produce these compounds called shortchange fatty acid that become absorbed and they're the primary food source for the intestinal cells. But as you can see, intestinal cells also produce this green substance, this mucus, and this provides a barrier to the microbiota because we don't want it to penetrate, we want it to keep it bay, but at the same time, we're so tightly linked to our bacteria that we feed it through our mucus. So, we've evolved to have a mucus that has compounds so that the bacteria can break down and here you see them as they're eating through this. And so, we have this really beautiful balance in this interaction, that the bacteria makes something for us and we also keep them safe within our gut environment.

[A second image shows a gut scan labelled "laxative treatment." It has a thin line of pale green mucus, and some mucus mixing with intestinal cells.]

What happens during the laxative treatment is a little bit like what I imagine for a tornado or for a tsunami. The laxative treatment causes such a large change in the ecosystem that it causes the stripping of this mucus layer, so now all these bacteria that before were separated from us become in contact, and this leads to a very strong immune response even against commensal bacteria that normally we like to keep close by. This also very much changes the way that bacteria can interact with our mucus. And like we know; these conditions have a time period associated with them.

[A third scan shows a gut titled "after recovery." A mucous barrier is wider but isn't as present in the bacteria.]

Once we stop taking these laxatives, the system reforms, but importantly, we'll see how this microbiota changes. The way that we assay how the microbiota is changed is by sequencing, so what we do is that we'll have these mouse models where we can inoculate them with a microbiota from a human patient. So, they start out without any microbes, and we added on a microbiota from humans so that we can actually look at specific patient microbiotas, as well as microbiota from mice too, to look at the broad set series of bacterial species.

[A new slide shows two graphs tracking bacteroidacae and muribaculaceae over days.]

Here, what I'm showing is a graph of how the abundance of this different micros will be changing. And the names are not really important, but I wanted to make sure to highlight them. So, muribaculaceae and bacteroidaceae are two families of bacteria that as you can see, make up a pretty large fraction of the microbiota. In fact, muribaculaceae starts out at almost 50% of the abundance, so every other bacterium belongs to this family.

And what we found is that during laxative treatment, these bacteria are completely depleted, we actually cannot find them in our system. And because this is a very competitive environment, the habitat that has been lost to the muribaculaceae is taken up by the bacteroidaceae. And what we were even more surprised to find is that even when we stop the laxative treatment, muribaculaceae are just lost and we cannot get them back. And so, here, I'm going to stop, because whether or not you care about the muribaculaceae specifically, this is a huge change to our microbiota. If I had to tell you about something like this that happened at a macroscale ecosystem, this would be akin to saying that all primates or all felines were going away from their habitat.

What we do know about the muribaculaceae is that they're disappearing from industrialized human communities. So, for example, in traditional communities that we find throughout the world, from Tanzania to the Amazons, muribaculaceae have a very high prevalence in these humans, between 65 and 90% of these humans have this family present. While in industrialized communities, they have very low prevalence. And of course, the question becomes, well, if we lose muribaculaceae, why is this a problem? Why should we care about having diverse communities of bacteria inside us? And this takes us back to the different scales of the problem. At the beginning of the talk, we talked about how the different lens scales between global and microscale have similarities, and now we're going to talk about the different time scales. So, for humans, one generation takes about 20 to 30 years, but for microbes, one generation is in the order of tens of minutes. What this means is that when we change our diet, when we take a laxative, when we change something about our lifestyle, the bacteria are going to adapt really quickly, but we don't.

Our lifestyle has been very much changed over the past 150 years due to industrialization, and our bacteria have adapted, and they produce different compounds because they're able to grow on different types of food, not anymore as much on fibre, but on processed foods. And the problem that has arisen is the fact that now our own biology is what is mismatched to our industrialized lifestyle. The key here is that there's really nothing fundamentally wrong or right with industrialized lifestyle, it's just that we have not evolved with it. And we think that because it mismatches our biology, the microbes that have been selected by industrialization produce compounds that can lead to inflammation, and so part of the problem is that we're selecting out the ones that were evolutionarily advantageous for our wellbeing, because they were helping us say, break down some of the roots that we would eat when we were hunter gatherers.

The key point here is that bacteria have changed in response to our change in lifestyle, but we, as humans, are not keeping up, and we think that is why we're seeing this incredible increase in inflammatory and immune system diseases. So, one question that then we ask is, does muribaculaceae actually play a role in these industrialized diseases? And this is a work that has mostly been led by Dr. Marty Blaser, who's at Rutgers University, and he works on a model with type 1 diabetes. One of the things that he found is that when this type 1 diabetes of the affectable mice are exposed to antibiotics, they have a much worse occurrence of disease.

[Another graph shows a diabetes-free probability over 30 weeks. Both a blue line representing mice on antibiotics and a yellow control line start at 100%. The blue line decreases much more than the yellow control line.]

And so, here is just showing it with this graph with the diabetes-free probability decreases when the mice are exposed to these antibiotics. So, here you can see that more mice are exposed or have a progression of the disease when they have antibiotics administered. This is in the dash blue line compared to the control. So, by the end of the experiment, only about 10% of the mice are diabetes free when they're exposed to antibiotics.

d one of the things that we thought that was really interesting is that depending on the presence of muribaculaceae, there was an association between diabetes development. So, the mice that did have muribaculaceae were much less likely to incur this disease. And this takes us a little bit back to one of the overarching themes of the field, is that we think that one of the reasons why we see so many more modern diseases have to do with the loss of some of these microbes. So, in the case of traditional populations, we have a complex and diverse microbiota compared to the loss of microbes that we have in industrialized diseases, and this comes with a two-sided coin, on one side, we don't have infectious diseases in the industrialised world, but at the same time, we have to fight the inflammatory diseases. And really, our goal here is trying to find a way to eliminate both infectious and inflammatory diseases.

So, this just takes us to the third vignette, which is thinking about the ecosystem restoration. This is a very hard problem, not only at the level of the global scale, but also the level of our own gut. If you think about probiotics that are sold all the time in supermarkets, they have been shown to only have limited efficacy and in some sense, this makes a lot of sense. If you were to think about a tornado or forest fires sweeping through Yellowstone, you can't just add a random species of rabbit and expect it to restore the ecosystem, and that's a little bit of what we're doing with probiotics, we're trying to insert a single species, and it might not colonize, in fact, a lot of the time it's just not able to colonize. And as you can see here, part of the reason why it's not able to colonize is that these communities are incredibly dense and incredibly competitive. So, this is a very hard task, and one of the questions that we ask in our research is when we lose muribaculaceae, can we actually get it back?

In our mouse model, doing this type of fecal microbiome transplants is really easy because it turns out that mice are coprophagic, meaning that they eat their own stool. Again, not the best topic before lunch, but I hope you'll come along with me with these experiments and these discoveries. In these experiments, by introducing more muribaculaceae, we really didn't know what to expect, because as I said, this community was very dense. But what we were really excited to find is that muribaculaceae was actually able to recolonize stably, and in fact, even more excitingly in this mouse model of type 1 diabetes, the reintroduction of muribaculaceae rescued the phenotype of the diabetes. In fact, the mice that had the antibiotics but then were given muribaculaceae a few days after did not develop the type 1 diabetes, so they were back at the normal rates without having been given the antibiotics.

[two graphs show abundance of muribaculaceae after antibiotics. They both dip at a beginning stretch highlighted in yellow. The graph on the left dives to zero and doesn't return. The graph on the right rises back to the 0.3 mark. A label on it reads "laxative treatment."]

An important lesson that we learned is the fact that reintroduction needs to occur in a non-perturbed environment to actually take hold. So, in these two experiments, we reintroduced muribaculaceae continuously over a period of several days, but in the experiment on the left, we only reintroduced it during the time of laxative treatment exposure, while in the second experiment on the right, we allowed this exposure to happen over only a couple of days extra, and muribaculaceae was able to come back out. So, what this really tells us and really informs us in thinking about what might be important for microbiota therapies is that we need to act in times when the environment is normalized. And now zooming back out in terms of thinking about restoring ecosystems, this makes a lot of sense. If you wanted to transplant a tropical forest into a desert, the desert better have water to support this growth. And we think about the microbiota in the same way, really focusing in on this ecosystem perspective.

So, what I've told you about today is that industrialization has changed our lifestyle, and this has affected our microbiota. I've told you also that over-the-counter drugs can lead to the disappearance of these key microbiota members, for example, in the case of muribaculaceae, and importantly, I've told you about that ecosystem restoration really requires this balanced physical environment. And I like to think about this from the perspective of what we're doing to the macroscale that I think is really helping. I really believe that the solution to the destruction of these ecosystems that has been cause by industrialization has to come through a respect and a better understanding of nature, coupled with improved technologies to allow humans and wildlife to coexist. And I think this important parallel also needs to happen for medicine and for microbiota. 

So, in medicine, we're very much seeing this large shift towards personalized medicine, but until our bodies evolve to require different stimuli, we will need to improve our diet and go back also to nature, alongside the improvements in our technology and our ability to restore our microbial diversity. So, I think for better or for worse, for a while longer, we'll have to eat our broccolis.

One of the things that also I would like to stress here is the fact that we need diverse teams to solve these problems. What microbiologists, and biomedical engineers, and doctors say alone is just not enough. What I think that we really need is to understand the psychology, the anthropological implications to lead to these system level changes and improve our lifestyle. One of the things that I think is very important is that we've known a lot of these lessons for a long time, by telling you that we need to eat healthy, I'm not telling you anything new, but we all know what happens to new years resolutions when they're about diet changes, they don't last very long. So, what I think that we need is really the legislation to implement these changes and make sure that they happen on a wide scale.

So, to end, I'd like to thank my team and thank the people that have made this event today possible. It's been a really wonderful experience. I trained in the States, and I was able to come back to Canada, and it's been super exciting to start a lab at UBC, and I'm really grateful for the opportunity to talk with everyone, and I'm looking forward to hearing your questions, and thanks so much for your attention.

[Carolina's screen share ends, returning to the chat panels.]

Marc Fortin: Well, thank you so much, Carolina. This is a fascinating topic and you've raised so many questions. Now speaking of questions, I'm told that we have a slight technical problem in that the raise hand function that I mentioned earlier appears not to be working at this moment. So, there is a different way for you, the audience, to send questions to us, and that's through email, we're going to go back to a good old-fashioned email and the email--

Carolina Tropini: Carrier pigeon works too, right?

Marc Fortin: Yeah, but we only have 30 minutes. So, we're going to work with email and the email address should show up on the screen. If it doesn't, the email address is C-S-P-A@C-D-N-H-O-S-T.ca. So, cspa@cdnhost.ca. So, please send those email questions and we'll do our best to answer as many as possible. I say we, it's going to be Carolina answering your questions, not so much we. But let me start with a couple of questions of my own, questions that come to mind as I listened to your presentation and as I think about the topic. You've talked about how environmental changes affect our microbiome, but could we come to a point where we purposefully change our microbiome through specific interventions where we try to achieve a health point? Can we, should we play, so to speak, or deliberately change our microbiome with drugs, chemicals, compounds? What do you think?

Carolina Tropini: Yeah, that's an excellent question. And I really like to think about this type of question based, again, on our understanding of natural ecosystems at a large scale. It's much easier to know when an ecosystem is really unstable than when it's a good ecosystem. So, if you had to say, compare two national parks and you ask which one is healthier, that's a really hard question, but you know when an ecosystem is not healthy. And this is the same thing within our microbiota, we know that there's certain signatures in the composition that will be affecting negatively, human health.

One of the ways in which I think that microbiota therapy can really act is at the level of newborn infants, so for example, one of the things that happens is that babies that are born via C-section started out with a much lower diversity of microbes and this later on has effects on allergies and asthma. And so, at that stage when the microbiota is really about to be formed, I think the microbiota therapy can really help to reinstate that diversity that we need for long-term health. But one of the challenges is that our microbiota is really dynamic and it's very persona, so our history very much affects what's "good" and what's bad. So, understanding the context and understanding the personality of our microbiota then becomes very important.

Marc Fortin: Mm-hmm. So, in the example of the C-section that you just mentioned, it would be possible to introduce diversity in the microbiome to avoid some of the issues like asthma and immunological conditions, so you think we can get to a point where we could do that?

Carolina Tropini: Yeah. Well, absolutely. And in some of the changes that we can do, in some sense we're modifying and engineering our microbiota every day, whenever we change our diet in a way that is significant, this will change the microbes that are present. And one of the goals, for example, particularly for prematurely born babies that may not be exposed to the normal microbiota that would go through the birth canal is to make sure that they have those microbes that help them protect from invaders. So, for example, in the case of necrotizing enterocolitis, which is a disease that affects a lot of premature babies, this comes from the lack of a microbiota that will be protective.

Marc Fortin: It's actually connected to a question that was asked by friends of ours who have a one-year-old, and that one-year-old essentially has been born in the pandemic context and has had limited contact with other children, other individuals. When we think back of day cares, day cares were a very diverse microbiological environment, very rich microbiological environment, but those newborns now in the last year have been less exposed, presumably, to diversity. So, what can those parents do to bring that diversity? And it's not necessarily a condition at this point, but they're worried about bringing the microbiological diversity that will be useful.

Carolina Tropini: Some of the research that is coming out and is really interesting shows that babies that are exposed to more microbes are healthier later on, and this has been really shown positively from the perspective of asthma and allergies. And part of the idea is that we have evolved in an environment that was very full of different microbes and our immune system needs to learn to attack and prevent infection from the right agents. And so, with something like allergies, the problem is our immune system has not been exposed to the right signals, and so it overreacts when it encounters other pollutants or allergens, even though it doesn't really have a good reason to be trying to fight them, to prevent- like, to make sure for our health. And some of the things that I think are really fascinating that connect us to the microbiota is that for example, kids that grew up with the dogs are much less likely to have allergies and asthma.

If a kid uses a pacifier, and particularly if that is being cleaned in the mouth of the mother, they're less likely to develop allergies. Second born kids are less likely to have these allergies. And everything points to the fact that what is the commonality here? Is that all these factors, as agents that bring microbes into the house help decrease the chances of this development of allergies. And one thing that is interesting with the pandemic is that of course, not only are we very separated from the rest of human communities, but also, we're using antimicrobial compounds far more. And this is of course, essential to prevent the spread of COVID, but also will prevent the spread of some of these microbes.

And so, this will have a societal impact, the challenge though, is that it's going to be a chronic effect, it's not an acute effect. And as humans, we're very good at dealing with acute effects and we can see this with COVID, how quickly people rallied up together to figure out a solution. But with chronic conditions, if you have to act on a specific day and decide, is this baby going to receive antibiotics? And try to solve something that could be acute right now versus this is going to affect their chances of becoming obese 20 years from now, the doctor is more likely going to choose, give the antibiotics now.

Marc Fortin: Mm-hmm. There's a question from the audience that I can relate to actually. Someone who's been bit by a tick, often the prescription is to take a course of antibiotics. Now, and it connects to the problem you were just raising, so there's a tick bite, and there's the possibility of Lyme disease, and then the person takes antibiotics, yet those antibiotics will have an impact on the microbiome. How can we still take those antibiotics? Because of course, we want to avoid Lyme disease, but what can we do to minimize the impact while taking the antibiotic? Minimize the impact on the microbiome? Is there any recipe, any tricks we can use?

Carolina Tropini: Yeah. Well, so I should preface this by saying that I'm not a medical doctor, so I can tell you what I would do, what my family would do, as well as what we've seen from the science. So, this is a very important question, and I think this is the direction where medicine needs to go, is that we're going to have to start keeping backups of our microbiota so that we can reimplant our microbiota after we've had to deplete it because of a colonoscopy prep, because of having to take doses of antibiotics, and so that we can save our work up until that point, and so then we would be to reinoculate ourself with our own microbiota. 

Marc Fortin: Mm-hmm.

Carolina Tropini: This has been shown with a lot of work from Israel, from the Segal and the Elinav labs where they saw that patients that were taking antibiotics were able to return to their normal state much faster if they were re-exposed to their normal microbiota, in fact, taking things like probiotics slow down with this recovery or change the course of it. And so, we're not there right now, fecal microbiota transplants are only used in situations of emergency. So, this is not going to help you right now if you've been bitten by a tick, and I'm sorry, it's a very scary occurrence, but some of the things that you can do is that I would probably err on the side of eating more diverse types of fibre, try to keep the microbes that you have in you there, try to keep them alive.

Other things that I think are really helpful is taking microbes in small doses, for example, fermented foods expose us to microbes in a way that our immune system responds to positively. So, there was a lot of work coming out from Stanford showing that the immune system actually gets activated in a way that is good for responding to infections by being exposed to these commensal microbes that come in yogurt, kimchi, and these other prebiotic foods. So, again, it's this balance of what our system is expecting to see, and this exposure to microbes is very important.

Marc Fortin: Carolina, we have an audience of public servants and I'm sure some of them come from regulatory agencies or policy making departments. What do regulators or governments need to know at this point? What do they need to prepare for? Because fairly often, we see the science moving quickly and the whole regulatory apparatus taking a little longer sometimes to catch up. So, what should regulators or governments know at this point or be prepared for? Should we consider limits on some compounds or some practices? What are your thoughts on that?

Carolina Tropini: I think limits on compounds is something that will have to happen. Again, going back to the responding to acute problems and how much we want to act. I think for both patients and the general populations, when there is the problem, the impetus is to try to act and take something, take a medicine, even though sometimes this problem will be resolving by itself. And so, I think where the regulations need to happen isn't to try to make sure that when we take compounds that might disrupt our microbiota, that we do it when we to do this, and then we don't do it just as a way of trying to do something for a problem that might be solved. And so, this is of course, not something that only affects legislators, but also affects doctors.

So, I think that we need to move into a regime that we understand more the interplay between our microbes and our health, and I think so much will be done as we try to push healthier diets in schools, in cafeterias, I think it really needs to be a system level change. I think they will see massive impact by promoting things that are already promoted, for example, breastfeeding for newborns, trying to reduce the number of C-sections, and all of these things that bring us back to what we have evolved with.

Marc Fortin: Mm-hmm. In a way- and you touched upon this in your response a second ago, in a way, when we were thinking about personalized medicine, I think many of us, I'll include myself, we were thinking of if we understand our genetic material, if we understand our DNA, then we will be better able to customize medical interventions to each one of us. So, if we understand our genetics, we can better prescribe interventions, but have we missed the fact that the microbiome is such an important component of our health and that we will no longer only have to understand our genetic material, but understand also the microbiological genetic material that's living within us?

Carolina Tropini: Yeah, Marc, that's a great point. And of course, I've drank a Kool-Aid for the microbiome, so I definitely think that this is going to be a very important factor. And even if just for the fact that these microbes will affect the way that drugs are delivered, so some microbes can change- most of the drugs that we look at will be changed by the microbiome, and even things we don't think very much about taking, for example, drinking diet drinks, we think that these don't affect us because they're sugars that human bodies cannot absorb, but in practice, the bacteria break them down and still give us calories for them. So, we're an integrated system, we can't get away from them, and we need to figure out how to work with them to make us healthier.

Marc Fortin: Integrated systems, those are always complex problems.

Carolina Tropini: Yes, very much so.

Marc Fortin: A question from the audience here, there's been a fair bit in the media about how the microbiome can influence mental health. What do you think are the possible mechanisms that explain these interactions between bacteria living in our guts and our mental health? What is the connection there?

Carolina Tropini: Yeah, that's a beautiful question, it's something that we're deeply interested in. And honestly, coming into the microbiota field, I was a little bit skeptical about this connection until it became really obvious how this would happen. So, again, whatever we produce in the gut makes it through our blood system, and a lot of compounds can cross the blood-brain barrier and affect our brain. And we see this really strongly, particularly in pediatric models of different inflammatory diseases. If some of the inflammation or some of the disease changes happen during development, and these affect the microbiota, and they affect the compounds that are produced, it turns out that a lot of the bacteria that produce anti-inflammatory compounds are bacteria that are not very good at dealing with that, with perturbations that can come through inflammation. And these are very specialized bacteria that basically, their main function in the gut is producing these anti-inflammatory compounds that up-taken by the intestinal cells.

And so, when these go missing, then these anti-inflammatory compounds are not present, and so exacerbates the inflammation, and this inflammation can also go through the brain. So, the relation is very complex, for example, in the case of neurodegenerative diseases such as Parkinson's, having a microbiota can actually be problematic, so there's been some studies showing that the use of antibiotics can actually be positive in the reducing symptoms. But in other cases, it can be really detrimental.

So, some work in my lab in collaboration with the Ciernia Lab at UBC, we're starting to show that early life inflammation changes the microbiota and leads to a memory deficit in these animals. And one of the things that we're investigating is whether the addition of some of the compounds that are normally produced by healthy microbiota can ameliorate some of these effects. And so, because so many of these effects compound over years of a changed microbiota, I think that we really need to address them early on in childhood and really make sure that we set up our kids with as much of the diversity that they need to be able to not have inflammation and not have some of the risks of these increased chances also of disorders of the brain.

Marc Fortin: Thank you. I want to go back to other questions from the audience, and there's two questions that are a bit linked. You've mentioned that the industrial revolution has had an impact on us, in fact, that was one of the title slides. So, for those of us in industrial societies, what can we do to prevent this erosion, or this decrease in diversity, in beneficial bacteria? And maybe a link to this is a large number of people take either laxatives or anti-acids, what are our choices to try to minimize the impact?

Carolina Tropini: Yeah, that's a very good question. And I don't think that there's a general answer. In some cases, I think that depending on specific conditions, there can be say, taking different types of fibre may be able to support your microbiota. But one of the things that I think it's really important that is happening in science right now is that we're trying to preserve the diversity that comes from these traditional populations and create banks of this microbes that are disappearing. And a challenge is that if we save them, what do we actually do with them? Let's say that we were able to resurrect mammoths, if we put them back in an ecosystem, what does that mean? Will it make it better? It's hard to know. And so, I think this is where we need to think about our early childhood development again because if we want to set up a diverse ecosystem from scratch so that we can bring it up and keep it as diverse and resilient as we can do it.

One of my kids was born by C-section and of course, I worried about the impact of the microbiota while I was there being opened up, I was like, "What did I do? I know that this is going to be problematic," and in practice, we have to adapt with our history, and so our microbes have been built up over multiple life occurrences of when we had to take antibiotics and times in which we had to take different medicines that will affect our microbiota, and we just can't prevent that from happening. But what we can do is to make healthier choices. 

For example, in perspective again, with kids taking laxatives, please feed your kids more veggies even though it's hard. There are choices on a day-to-day basis where we- it's not the easiest choice, industrialization has brought on a lot of easy choices, but where we can do better. So, for example, instead of taking laxatives, need to have better options for veggies that busy parents can do when they are trying to force down a carrot down the kid's mouth. And so, this collaboration between technology development, and legislation, and doctors really needs to happen in a concerted way so that we can make sure that the easy choice is also the choice that is better for our health.

Marc Fortin: That's an absolutely perfect segue to another question from the audience. So, you're talking about multidisciplinary approaches, or different lenses to attacking this problem or to addressing this problem, yet we know it's difficult. I mean, researchers are busy doing research, GPs are busy in their practices in their clinics, and they are really busy right now with all kinds of challenges, regulators, and so on so forth. Is there any source of inspiration, anything that you have seen in different parts of the world, where we are able to bring those different disciplines, those different lenses that all need to work together in a complimentary way? Is there any source of inspiration, anything you've seen that could inspire us in Canada about doing things differently? About [crosstalk 00:52:39] bringing all those people together? I'm sorry.

Carolina Tropini: Well, like I said, I don't mean to toot my own horn, but CIFAR has been amazing at that. And it's very much the goal of CIFAR, is to bring people together from different perspectives to ensure that some of these important public health agendas come through. And so, through CIFAR, some of the things that we're doing is, for example, developing curricula to teach about the microbiota to new doctors that are coming through a public health curriculum. And more of this needs to happen, I think that now it's just become plainly obvious that these problems are much bigger than the microbiology can solve. And the other part, which I feel very strongly about and is the reason why I'm here is that as the researchers, we can't just keep staying in universities and just do our science, we're living in an era of disinformation, and the voices of people that are directly studying this work needs to come out, and it's our responsibility to make sure that this work does come out, and that we work with the stakeholders such that these problems can be solved.

And so, I'm a strong believer that the research doesn't just belong within the universities, that the public needs to be involved, and that if we want to see more progress, that the next boundaries are so big that all the low hanging fruits have been taken, we've had many years of research, now we are on to a new type of science.

Marc Fortin: Carolina, this is so important, and I cannot agree with you more. I spent most of my career as a researcher and now I'm in the federal system because I do believe that researchers, scientists do need to bring their message and their lens to the greater government and to influence a greater system. So, I'm really grateful for you taking the time out of your very busy life to step out of your lab and work with us in government. It's been an extraordinarily informative session, Carolina, I can't thank you enough for your presentation, for your time.

We also want to thank CIFAR, the partner with the Canada School of Public Service for helping the school bring these events to this audience. We want to of course, thank you, the audience for participating in very large numbers today. And your feedback is always welcome and it's important to us, so you'll be invited to complete an evaluation through an email that will come to you in the next few days. And please, do consult the webpage for other courses, events, programmes that the Canada School for Public Service offers.

The next event in this series of Canada, at the Cutting Edge will be broadcast on Tuesday, January 25th, on the topic of quantum information. And the event will be moderated by one of my colleagues, Dr. Nipun Vats, assistant deputy minister at ISED, and will feature Dr. Stephanie Simmons, a Canada research chair in the physics department at Simon Fraser University, so more details on registration will be posted on the website. Carolina, so many thanks to you for the work that you do, for your passion, and for your willingness to communicate. Thank you to the audience, thank you to CIFAR, and thank you to the Canada School for Public Service. Enjoy the rest of your day.

Carolina Tropini: Thanks so much for having me.

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