Believe the Impossible: The Future of… human gut health
Carolina Tropini, a fellow in CIFAR’s Humans & the Microbiome program, gives insights in studying the human microbiota, and the potential it holds in precision medicine
In graduate school, Carolina Tropini originally wanted to stay as far away from studying bacteria as possible.
“The work that I saw first hand was just people researching E. coli. And I thought, this system is too simple,” said Tropini, CIFAR Fellow in the Humans & the Microbiome (HMB) program. “I had a lot of misconceptions about bacteria at that point.”
In fact, the human microbiome — millions of tiny life forms, such as bacteria, viruses and fungi that cover the human skin and live within the body — is a field with so much potential for medical discovery, and researchers are working to better understand this vibrant microscopic community.
Tropini, an assistant professor at the University of British Columbia and a former CIFAR Azrieli Global Scholar (2019-2021), is among those who are using cutting-edge experimental techniques to study the microbiota in order to determine the mechanisms of transmission of bacteria between hosts in health and disease.
In a Q&A with CIFAR, Tropini shares insights on her current projects and the impossible questions she hopes to answer in her work.
CIFAR: What motivates and inspires your work right now?
Carolina Tropini: I’d say it’s twofold. One, it’s the people who are super important to me. I feel really privileged to work with students on their paths toward becoming scientists.
The other part is the gut microbiota, I feel this is such an exciting field for discovery. And one of the things that I like the most about it is that it’s been almost a rediscovery of what it means to be human. I like to think about us as these ecosystems that are walking around other bigger ecosystems. The chance to learn how we’re all interconnected in this way is really beautiful — the study of our health that is both within us, but also bigger than us.
Microbes can be problematic and microbes can be useful for our health. It’s endlessly fascinating. For example, we get to better understand the science behind some of the lessons we learned growing up, like my grandma telling me I should eat my veggies. Ultimately, we are feeding our microbiota and helping it make compounds that keep us healthy. Understanding why that matters, and how this is mediated through other organisms that allow us to function correctly — that stuff excites me.
CIFAR: How well is our gut understood? What is left to investigate?
Carolina Tropini: We still really don’t know some of the basics, but we’re starting to know enough that we’re working towards what I think is going to be really exciting — precision medicine through microbiota therapy.
Let’s say that I have a specific disease. Precision medicine is when we can specifically modify our microbiota so that, for example, it naturally triggers the immune system in a way that is beneficial. Or, we could even engineer a microbiota member to produce something to ameliorate inflammation if there’s a flare-up in a chronic disease.
CIFAR: Can you give an example of a chronic disease precision medicine could be applied to in the future?
Carolina Tropini: We study inflammatory bowel disease (IBD), which is a chronic condition that is incredibly difficult and painful for patients. It leads to inflammation in different parts of the digestive tract.
We know that in IBD, the microbiota becomes a very non-diverse community of microorganisms and further exacerbates the inflammation. Alongside a very strong immune system component, this is a very complex disease that is very, very different from person to person. We are working to leverage the ability of the microbiota to modify its surrounding environment and reduce the inflammation, so that the gut can become receptive to other therapies that can help patients recover. Without changing the environment, more sensitive beneficial microbes are unable to take hold, just like transplanting a forest into the desert requires
ameliorating the soil first.
CIFAR: What have you seen in your field that seemed impossible but is now real?
Carolina Tropini: I think something we are getting close to achieving is the ability to predict complex systems. To give you a practical example: let’s say that an area in Yellowstone has been disrupted by a fire. What should you reinsert into that community first to make it flourish as it was before? If we understand the predictability of these complex systems, we could take steps to make them healthy again with fewer risks of unintended consequences.
So going back to the Yellowstone analogy, if I add some rabbits, what is going to happen to the plant population and what is going to happen to the predator population? This is like us thinking about the gut, “we’re going to add this species of lactobacillus (a type of probiotic), and we’re going to do this to work towards this final effect.”
CIFAR: Tell me about your current projects.
Carolina Tropini: We have projects that span from the single-cell level, and all the way up to looking at the systems in complex communities, to looking into animal models, to clinical application.
We’re interested in understanding, from a basic perspective, how the physical environment that our gut provides influences the microbiota, as well as how our microbiota influences our health.
For example, when you have a fever, your microbiota experiences this very high change in temperature. These microbes can replicate and produce a new generation in a matter of 10s of minutes. And so, if you have a fever for a couple of days, it’s basically as if there was global warming happening within your body. There’s such a large-scale effect on organisms within your body that are dividing quickly.
So something like a chronic disease can really modify your gut ecosystem based on what would even seemingly be small changes — say a fever or a two-degree change of body temperature. That can really affect your microbiota composition. And then that, in turn, changes what the microbiota makes. And because we’re so tightly interconnected with what they make, that impacts our health.
CIFAR: Is there such a thing as a “healthy” gut? What makes for a healthy microbiota community?
Carolina Tropini: It’s a great question and a controversial question in the field, because everyone would like there to be a healthy microbiota but we know it’s not that simple. There are many ways in which you can have a healthy microbiota, and in fact, different people may need to eat different things to keep themselves healthy. That depends on the history of their microbiota, their immune system, and genetics. And so, there’s not going to be a one-size-fits-all. We’re all our own individual ecosystems. And I think that’s super exciting because it means that there’s a lot of possibilities for being healthy. It also adds a lot of complexities as a researcher to understand.
CIFAR: How has being a part of the HMB program helped you in advancing your research?
Carolina Tropini: The program has really been amazing. The world around and inside us is inherently interdisciplinary, so having the opportunity to discuss questions around the microbiota with people from very different backgrounds and then finding connections, is really incredible. For example, we recently published an article on how the COVID-19 pandemic may have unexpected effects on our microbiota due to reduced contact and uneven societal impact, which could in turn affect our long-term health and social outcomes. The chance to discuss these topics with biologists, anthropologists, social scientists, doctors, and more, takes the research in completely different directions and out of the box.
As part of CIFAR’s 40th anniversary celebration, “Believe the Impossible: The Future of…” highlights researchers whose big ideas could transform their field over the next 40 years.
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