Ancient Microbiomes and Modern Medicine

Penn State undergrad Thomas Sontag  interviews associate professor of anthropology Laura Weyrich  about her research on  the history of our microbiomes and explains why it holds relevance to contemporary medicine.

Thomas Sontag
Undergraduate student at Penn State double majoring in Microbiology and German

Laura Weyrich
Associate Professor of Anthropology at Penn State

Transcript

Mark Shriver:

From the Center for Human Evolution and Diversity at Penn State, this is Tracking Traits. 

[THEME MUSIC]

Cole Hons:

Greetings fellow Homo sapiens, this is Cole Hons from The Huck Institutes of the Life Sciences. Welcome back to the podcast. 

For episode five of our third season, Penn State Biology undergrad Thomas Sontag returns, interviewing Laura Weyrich, associate professor of anthropology at Penn State. Weyrich’s research focuses on reconstructing ancient oral microbiomes and supporting ancient DNA analysis of past humans, environments, and animals.

In this podcast conversation with Tom, Weyrich explains how studying the history of our microbiomes holds relevance to modern medicine. She also discusses the sourcing of samples for studying ancient microbiomes, including ethical issues related to ancient DNA research. She unpacks the interdisciplinary nature of her research, and finally she reflects on the importance of maintaining resilience and passion when pursuing a career in science. 

Here's Thomas Sontag interviewing Laura Weyrich about “Ancient Microbiomes and Modern Medicine.”

[TRANSITION MUSIC]

Tom Sontag:

Thanks a lot for being here today, Laura. To start things off, do you think we could hear a little bit about your research?

Laura Weyrich:

Yeah. Thanks so much for having me today, Tom. I really appreciate it. My research focuses on reconstructing ancient microbial communities. We want to know about the bacteria, viruses, and fungi that lived in past people, but also in past environments and animals. And we refer to those microbial communities as microbiomes.

Tom Sontag:

That gets me thinking, where do you even get the samples you need to study ancient... Let me reread that. That gets me thinking, where do you even get the samples you need to study ancient microbiomes? I can't imagine they're easy to come by.

Laura Weyrich:

They're not. So if we're interested in studying ancient microbiomes that lived within humans, we have to actually go in and visit ancestors that have died long ago and clean their teeth. So we perform a bit of ancient dentistry to remove calcified dental plaque from their teeth. This is a complex process. We have to have interactions with communities and the descendants of these individuals, but we often also work with museums and other agencies that hold these collections and take care of them over time. So that can be a complex process, but it's really exciting and really fun to be able to work with all of these people, and be able to clean the teeth of people who've lived long ago. If we're studying ancient microbiomes in environmental contexts, we will go out into the field and help collect those samples. So we'll do coring to look at ancient, for example, soil or sediment microbial communities. We've also done Antarctic ice, and even looked at calcium deposits on the bottom of glaciers in Antarctica.

Tom Sontag:

Wait, so you've even gone to Antarctica? Can you tell us a bit more about that?

Laura Weyrich:

I haven't been lucky enough to go myself, but we've worked with collaborators who've been working down in Antarctica, and using the samples that they collect there as proxies for long-term climate change. So if we can understand what sort of minerals and elements are being released, especially into the oceans in Antarctica, we might be able to understand more about ocean circulation as well as the health of our oceans. And microbes are a really interesting part of that process. So microbes can both be deposited from the air and ice, and then captured in time capsules of glaciers over time, but they can also be part of the geochemical processes underneath glaciers that help break down rocks and minerals as the glaciers are moving across the landscape. So we can use microbes in lots of creative ways to tell us more about the processes that are going on and how that might relate to larger scale, big picture changes in climate. We really are understanding the processes at both a micro level as well as a global level.

Tom Sontag:

I see. This topic sure is interesting, and it makes me think that maybe a lot of emphasis has been put on human genetics throughout the past, but maybe there should be a greater focus on the history of our microbiome. How is the history of our microbiomes relevant to medicine?

Laura Weyrich:

I think you're completely right that we need to have more emphasis on the types of microbial communities that people carried with them in the past. And this is the large part of what my team does, is really understand these microbial communities that lived within humans over long, long time spans. And so the latest my lab has been able to go back is about 48,000 years ago, when we were able to reconstruct microbial communities of Neanderthals that lived in Belgium at that time. But we can really begin to piece together the origins of disease. And this is really critical for us today, especially when we're thinking about modern medicine, because many of the diseases that we face are not infectious any more. A lot of them are chronic long-term diseases, and they involve the microbiome. So these trillions of microbes that live within the human body contribute to many of our daily functions, and if we alter those microbial communities, and therefore alter those functions, we can then get associations to disease.

And so we want to know, when were those microbial communities altered, and why? It could be that processes that were put in place, for example, during the Industrial Revolution or during the Great Acceleration or after World War II, are actually what's driving some of our health issues today. A good example of that, for those of you that are listening, would be the Industrial Revolution. At that time, we mechanized the production of food, and we started sterilizing a lot of it. And so instead of eating lots of natural microbes from food that's grown locally, we started eating very sterile food. And we think that may have a lot to do with shifting the types of microbes that we have.

We also got sugar in large, large quantities at that time, and so it probably shifted again the types of microbes that we see in our body. Even past World War II, if we're thinking about the oral microbiome, we see that dental hygiene really kicked into high gear and really started the processes that we attribute to modern day oral health practices like toothbrushing. That's something that really started only after World War II, and probably plays a role in the types of microbes that we carry with us today.

Tom Sontag:

And from studying microbiology, I know that the microbiome in the mouth is very much connected to a person's diet. So I was thinking, do you get to learn about ancient diets while studying ancient microbiomes?

Laura Weyrich:

Yeah, that's a really great question. That's actually a dogma in the field that my lab has helped overturn. When I started in this field, dentists told me that the oral microbiome doesn't change according to your diet. And that was largely thought of because many oral microbes in the mouth live off salivary proteins, so things that the human body itself produces. And so they thought, the food in your mouth is really fleeting, it doesn't stay around very long, and that maybe a lot of the microbial relationships to diet are really in the gut and not in the mouth. And a lot of our work, as well as some really amazing work from other labs around the world, has really fought against that and really showed that the nutrients that pass through your mouth and the food that you chew really does stick around for a while, and it does influence the types of microbes that we see in our mouths.

And so we can use that information in a lot of different ways. One is that we can actually use the functions in the microbes to predict what sort of diet people may have had in the past. For example, if you drink milk, you have lots of microbes in your mouth that also can digest lactose, one of the key components of milk. And that really allows us to determine whether or not somebody was drinking milk, if they have microbes in their mouth that were eating milk. It's kind of, you are what you eat, but your microbes also are what you eat.

We can also in ancient calculus go in and actually find DNA that doesn't necessarily correspond to the microbes, but stuck between your teeth we can also find the DNA that corresponds to the plants or the animals that you might have been eating. Now, technically that's a much more difficult process. And in fact, we've done a lot of work to try to clarify a lot of these technical, often computational issues that we run into when we're trying to do this sort of analysis. But it is possible to find pieces of dietary DNA we call it in stuff between our teeth, and really be able to reconstruct, not only the microbes that somebody had, but also maybe some specific dietary inputs, things like mouflon sheep in Europe, or things like grains in people who are practicing early agriculture.

Tom Sontag:

And it seems like there's a wide range of periods and cultures you can study. Is there any particular culture you want to study?

Laura Weyrich:

That's a great question. I'm really excited about a lot of our work happening currently in South America, especially on the west coast of South America. A lot of the research that's been done in ancient DNA to date has been done in European populations, and that's told us an amazing story about how microbes have come to be in those populations. But the story in other parts of the world is going to be different. We know that these microbes have co-evolved with our human bodies over millennia, so we really need to go in and look and see, what is the story in other countries prior to the colonial era, and prior to Europeans arriving and many of the other continents in the world?

The colonial era when Europeans spread things like smallpox and other infectious diseases around the world is really well known. But what's not well known is how many of these non-infectious microbes were also spread throughout the world. It's really important for us to dig in and understand how other communities' microbiomes may have been changed by European influence, through both direct spread of microbes, but also through significant selection in the diet and environment in which people were living. So I'm really excited about our work in conjunction with indigenous communities, as well as local partners in some of these areas, to reconstruct microbial communities in non-European populations.

Tom Sontag:

Do you think that could help us understand and fight current diseases?

Laura Weyrich:

I absolutely do. There's something called the indigenous health gap, where indigenous communities and people worldwide globally suffer from many of these chronic Western industrialized diseases at a much higher rate than, say, Caucasian European populations do. And so we really think that tracking back the history of these microbial communities will allow us to see how and why these diseases started from the first place, where their origins lie. That's really, really important for being able to differentially treat diseases across different populations, and also understanding the magnitude and multitude of ways that microbes can contribute to disease. Many of these mechanisms are still unknown and we're still uncovering them, and being able to do that in the past as well as the present really allows us to widen our field of view.

Tom Sontag:

And it seems to me that your research is at a crossroads between many different fields, like anthropology, microbiology, archeology, and molecular biology. Is it difficult for lab members to learn about all these different fields?

 Laura Weyrich:

That's a great question, because I often have to tell people that I wear multiple hats. I'm a professor of anthropology and of bioethics, and I'm also a co-hire with the Huck Institute of Life Sciences, where I can focus more on the microbiology, molecular biology, and even immunology of some of the diseases that we're studying. So my team consists of people who've been brought in from, A, all around the world, but B, also from different backgrounds and different expertises. And we really work collectively together as a team to share that knowledge across individuals, and also develop our skills using the support of some of our team members.

So for example, I wasn't able to formally train in archeology or anthropology. Most of that work had to come during my postdoctoral research, where I trained with people in the field, and didn't necessarily sit in a classroom and learn about these things. So I would say learning on anything is possible, but it's all about how we provide access and how we work together as a team, to make sure that we can perform interdisciplinary research at a really high level. My students committees usually also are very diverse. It's people all across campus sitting on them, and working together again to find solutions that leverage knowledge across many different research fields in order for our work to continue on.

Tom Sontag:

Can I just follow up something? In one of the previous interviews we did for this podcast, we interviewed Dr. Powell about how different peoples have different diets, and for instance how people in Africa might be better adapted to different diets. Do you think that's related to how some microbiomes change with different peoples and regions?

Laura Weyrich:

Yeah, that's really interesting. And I do think that the microbiome plays a key role in our ability to adapt to different diets in different parts of the world. So depending on the types of food you eat, depends on the type of nutrients you have and also the fiber content of your food, and that's going to contribute to the types of microbes you have that can be successful, given those nutrients and given those inputs into their system. So for us, we really think that the microbes you carry with you are a representation of that adaptation, to not only your environment, but also your local diet.

So even today, if we're looking at people who do not have industrialized lifestyles, and people who practice quite often traditional lifestyles, they have very different microbiomes to one another compared to folks who live in industrialized countries. If you live in an industrialized country, your microbiome is much more similar to anyone else living in an industrialized country than it is to people who practice traditional lifestyles. So we really do think these microbes are a reflection of that adaptation, and also really allow us to access different food sources. So they play a really critical role in how we're able to eat different diets and how we can be successful using those different diets.

Tom Sontag:

Aside from how you need to learn many different fields, are there any other hardships specific to this field?

Laura Weyrich:

For us right now, it's really important to get the ethics right of ancient DNA research. And so I've been part of an ancient DNA ethics grant funded by the National Science Foundation in order for us to really dig in and figure out, what are the best practices to ethically conduct ancient DNA research? Just like many other scientific fields, ancient DNA research is really born out of colonial practices, and is born out of museums who have exploited indigenous peoples in some ways. And so we're working to really revamp the system, and really think hard and work with indigenous partners to hear their voices, and really understand what are the best practices forward.

We have a lot of work to do, I would say, to be able to practice ancient DNA ethically, and my team is certainly working and trying to improve our methods on a constant basis, to really ensure that we are not causing harm to any people, and that we're asking questions that are beneficial, not just to my own research team, but also to local communities. So we really see these as forming partnerships. But I would say that everybody in the ancient DNA field hasn't done these historically, and that's currently a really big hardship, is to get everybody on the same field and make sure that we're not causing any harms to, for example, descendant populations who may not want ancient DNA research done.

Tom Sontag:

I know from experience that being part of a lab can take up a lot of time, and from what I've heard from the head of the lab I'm in, running a lab is even worse. How do you balance research and your personal life?

Laura Weyrich:

That's so true. It is a lot of work, and especially when we're running an ancient DNA lab, which is a purpose-built ultra-technical lab, it gets even more complicated. So it is an active process to try to balance my personal life and my work. I'm of course very passionate about my work, and I often think if you are fortunate enough to have a job that really ties to your passions, then work doesn't feel like work. So I'm very fortunate in that way. But I also have a six-year-old and a three-year-old at home who need their mom and who need to grow up in a happy, healthy family.

So it's an active process. I'm somebody who really budgets my time very specifically to make sure that I can meet deadlines and get things done. And I also try to make sure I can meet the needs of my team, and making sure that I'm providing time for my graduate students, postdocs, and my technicians. So it really is about, for me, being very time efficient and scheduling my time, and working with people to understand their needs and deadlines so that we can meet them together as a team.

Tom Sontag:

And what aspect of your research excites you the most?

Laura Weyrich:

I am really excited about being able to develop what we call oral microbiome transplantation technology. So we are using all of this information from the past, and from indigenous communities that we're working with today, to understand the true origins of things like oral disease, like dental cavities or periodontal disease or gingivitis, and take that information and leverage it into new modern dental treatments.

And so one of the ways you can do this is by thinking about replacing the types of microbes that are in someone's mouth that may be causing them to have disease or causing them pain or discomfort in some way. And so I have a grant funded by the National Health and Medical Research Council in Australia that's been developing these oral microbiome transplantations in conjunction with the University of Adelaide. We are just so excited about what this might mean five or ten years from now, when we might be able to replace the types of oral microbes that are in people's mouths who are suffering from disease, and transition them into something that really supports their health, both orally and systemically. I really do think that someday we might be pushing to the point where we may not need to brush our teeth anymore. We may not need to visit the dentist several times a year to clean the dental plaque and calculus off our teeth. We may just need to make sure we have the right microbes in our mouths.

Tom Sontag:

So Laura, I don't think when you were young, you just woke up one day and said, "I think I'm going to study ancient microbiomes." So what's the story? How did you get interested into this area?

Laura Weyrich:

Yeah. I never woke up as a kid thinking I wanted to clean the teeth of skeletons. I did, when I was in kindergarten, think I wanted to be a dentist for quite a few years, and then that somehow during middle school and high school transitioned into me wanting to be a doctor. So I actually started my undergraduate career thinking I wanted to go into medicine, and actually was a pre-med student. And about the same time, my grandfather actually passed away from Alzheimer's. And so I spent a lot of time in hospitals, I spent a lot of time in nursing homes. And one of the things that really frustrated me about that experience was just the lack of doctors' abilities to be able to really treat the issue of the disease rather than treat the symptoms.

And so doctors do a lot of amazing, phenomenal work to help people be more comfortable, especially when they're suffering from terminal diseases and things along those lines. But what I really wanted to do was figure out how to actually treat the root cause, to be able to do research and really figure out, what's truly causing the disease, and how do we stop that? Rather than, how do we continue to patch or just treat symptoms of a disease?

And so during my undergraduate degree, I decided to switch majors, and I switched over to being a microbiology major, and that included environmental and industrial microbiology at the time, because I was really interested in how we might make pharmaceuticals from microbes. And I did my undergraduate degree at South Dakota State University, and had a really awesome experience and many different research experiences as well. So I got to, for example, trap mosquitoes and be part of a team that tested them for West Nile disease, to do West Nile surveillance across the state of South Dakota. And I also was part of a team that looked at animal microbiomes in very early days, prior to high throughput sequencing. And so we were looking at the types of microbes that pigs carry in them, especially when you changed their diet. And we were using some really old school culture methods to do that. But that really seeded into me this idea of the microbiome, and how important it might be for health and disease.

So I was really interested in studying the microbiome when I came to Penn State to do my PhD, and I thought I would study maybe potentially even more environmental microbes to really be able to, again, look for new pharmaceuticals or new treatments for diseases. But I ended up working in an infectious disease lab here at Penn State, and that was in the biochemistry, microbiology, and molecular biology department. And I was able to study whooping cough, or Bordetella pertussis, and kennel cough, which is Bordetella bronchiseptica. And we really looked at how the microbiome might be used to both prevent infection, but also how the microbiome responds during infection, and how that may alter the immune response.

Throughout my PhD though, I had to do a lot of work in mice, and I applaud the folks who are able to do that, but it was not something I wanted to continue doing in my career. And so I was looking for postdoctoral opportunities that really leveraged research in humans. If we were going to understand, again, how the microbiome changed in humans and how it's related to human diseases, in my mind we needed to look at humans. Mice do a lot of weird things that humans don't do, including things like eat their own feces. So we really wanted to look at what's happening in humans. And a position at the University of Adelaide was advertised to really use ancient humans as a model system to understand how and why human microbiomes change. And I just thought, gosh, what a phenomenal opportunity to be able to look at experiments, natural experiments that have already been run in the past. I don't have to set the experiments up, we just have to go in and look at the results, and look at what has actually happened in a real world scenario.

And so I moved myself and my partner all the way over to the other side of the world, to Adelaide, Australia at the University of Adelaide, and was able to do a postdoc there. And throughout that experience, I learned a lot about archeology and a lot about anthropology, and I was able to take some bioethics skills I developed here at Penn State during my PhD, and really apply those in an ancient DNA context, and got to where I currently am.

And so even though looking at ancient humans and how their microbiomes respond is a unique thing, I really feel like it has so many applications across so many different fields. So one of my goals at Penn State is really to make sure that ancient DNA research is accessible to anyone who wants to use it. And it doesn't matter what field you're in or what your end goal is or what results you'd like to get of it, I think this evolutionary lens can be really powerful. So I went from being a dentist, or a kid who wanted to be a dentist when I was in first grade, through to scraping the teeth of people and looking at the microbes that are present in their mouths. But it's a long path, and it's one that's filled with a lot of really great experiences and a lot of really wonderful mentors that sat down and talked with me about where I wanted to go in my career and how I might be successful.

Tom Sontag:

And do you have any advice for any young people who are thinking about becoming scientists in the future?

Laura Weyrich:

That's a great question. I often tell students that are interviewing to be part of my lab that you need to, A, really enjoy the environment that you're going into. And so if you're going to join a lab, you need to make sure you've got a good relationship with your PI or your mentor, and that it's really an environment that you're happy to go to work in every single day. But I also tell students that I think the single biggest trait that they can have to make it through grad school or be successful in research is really resilience. Many experiments that we run will not work out. Many things will fail in the lab. Many analyses will give you the opposite result you thought you were going to get. And having the ability to come back to it time and time and time again is really, really important. Your applications might also not be successful, and you've got to have resilience to resubmit them and know that someday it'll work out.

The last thing I also tell people is to follow your passions. If you're not passionate about what you're doing and you don't absolutely love it with every bone of your body, then it might not be the sort of field for you. And I encourage students to keep looking for what that passion truly is, and keep trying to figure out, what am I going to be so excited to get up out of bed in the morning and do every single day, hopefully for the rest of your life? If not, that's okay. Find that new passion and follow that new path. But doing something that you truly love I think is really, really critical and really important for anyone's success, including students.

Tom Sontag:

So do you have any predictions for future developments in the field? I mean, things that might come in 10 years or 20 years?

 Laura Weyrich:

I think it's going to be very interesting to look at how we support the growth of beneficial microbes in the mouth, and also use non-conventional ways of destroying particular microbes that we want to get rid of. So when we brush our teeth and we use toothpaste, it's very antimicrobial. Mouthwash, very antimicrobial. We're destroying everything that's present in the mouth. And I think over thousands of years of selection, if we're looking way into the future, that that's probably not going to do us any good. We're probably selecting for microbes that are resistant to those processes.

So how do we support these beneficial microbes? And how do we go in and not get rid of the whole microbiome, but rather targeted individual microbes that might be causing disease? For example, porphyromonas gingivalis is a microbe that's been linked to periodontal disease, and I know there's teams around the world right now working on viruses that just target that individual microbe. If we can knock that microbe out of our microbiome, it might mean that we can cure disease without even having to do an entire microbial transplantation. I would say we're at least 10-ish years away from those sort of developments though, and having them rolled out in the clinic, but I'm really excited to see where that research goes.

Tom Sontag:

And if I heard correctly, you're a bit of a pioneer in the field, is that right?

Laura Weyrich:

That's quite the compliment, and I like to think that I've worked with a really amazing team of folks who've all contributed to this. But I was part of the first study in 2013 that was able to apply these techniques that we've developed today in ancient dental calculus, and really describe using genetics the microbes that our ancestors carried with us. I was also the first person to reconstruct the microbiome of an extinct species, Neanderthals. And so that's, again, an incredibly exciting area of research that wouldn't have been possible without a very talented group of people all working towards the same goal. So I'm lucky that my name's the first author on the paper, but I'm just so fortunate to work with many people who are all contributing.

Tom Sontag:

That's very impressive. Now, one last thing. Is there anything your lab is studying or will be researching in the future that you'd like to tell us about?

Laura Weyrich:

I think I'm most excited about what we're going to uncover about the recent past, and this is really an open area of research in my field. We have been so focused on what's happened over the last 10,000 years or the last 50,000 years, and that's really interesting and really informative. But we also need to understand what happened in the last 50 years or the last 100 years. And so I'm really excited about what we can do by working with dental colleges and medical schools to revisit some recent ancestors, and really understand how very recent changes, really things that our parents were exposed to or even our grandparents were exposed to, may influence our health today, and how the microbiome may have contributed to that. So I'm really excited about that. I'm also very excited about much more deep in time. I really want to see an oral microbiome of a Denisovan or of Homo erectus or of Homo heidelbergensis published sometime in the near future, because I think that's going to help us unlock how our relationships with other hominid species really contributed to the types of microbes we have today in our mouths.

Tom Sontag:

All right. Thanks a lot for telling us about your research. I think we learned a lot about the importance of looking at microbes to understand our past, and also about combining knowledge from a variety of different fields of biology.

Laura Weyrich:

Thanks so much for having me today, Tom. It was great fun.