SciCafe: How "Paleo" is Your Diet?
by AMNH on
Evolutionary biologists argue that no study of human health or evolution is complete without considering the trillions of microbes that live in us or on us—our microbiome. In this SciCafe, join molecular anthropologist Christina Warinner as she explores how scientists are reconstructing the ancestral human microbiome to better understand the lives and health of our ancestors.
This lecture took place at the Museum on April 6, 2016.
Watch a video version here:
The SciCafe Series is proudly sponsored by Judy and Josh Weston.
This SciCafe event is presented in collaboration with The Leakey Foundation.
SciCafe: How “Paleo” is Your Diet?, The Secret World Inside You, and related activities are generously supported by the Science Education Partnership Award (SEPA) program of the National Institutes of Health (NIH).
Additionally, there's been some very interesting recent work connecting the oral microbiome and the gut microbiome to cardiovascular disease. There's several recent studies that tested cardiovascular plaques; arterial plaques, and found that more than 80 percent of them contain oral bacteria. There seems to be a connection between transient bacteremia that occur during tooth brushing and flossing. These bacteria can travel to your heart where they can then colonize briefly your arterial tissue and cause irritation and stimulate plaque formation. So, the microbiome clearly plays an important role in human biology and in human evolution. But we don't know very much about how it's changed through time. So, this is something that's really fascinated me because I am a molecular anthropologist, and I focus on ancient DNA. And I wanted to use these techniques and see if I can go into the archaeological past and actually reconstruct the microbiome at different points to help us understand how it's changed through time and to confirm some of these hypothesis that we've been formulating about major changes that might have occurred in the archaeological record and at what point they occurred and what stimuli caused them. Now, archaeologists and people who focus on ancient DNA primarily study bones and teeth. And there's a very good reason for that, and that's because mainly that's what we have in the archaeological record. That's the primary form of human remains that we have. And we've learned an awful lot from bones and teeth. We've been able to take these and reconstruct the genomes of extinct animals, the genomes of archaic humans. And we've even been able to reconstruct pathogens that infected humans and plants long ago. But how are we going to get to ancient microbiota? As we said earlier, microbes don't typically fossilize. How do you find them? The human body itself rapidly decomposes after death. And it's true that in some cases we get mummification, but mummification's actually quite rare. It's limited to only a few places and time periods, predominantly in ancient Egypt and ancient Peru. And in the vast majority of cases, what we're really left with is just a skeleton. A skeleton itself does not have a microbiome. And so this research really stalled for a long time, and no one really knew how to move forward. But there are a couple of substrates that do preserve in the archaeological record. One is paleofeces or coprolites. Sometimes it is not common, and it only occurs in some cases, but feces can preserve, especially if they are dried out very rapidly in the archaeological record. And we do sometimes find paleofeces in archeological deposits in dry caves or in salt mines; prehistoric salt mines. But like I said, they're quite rare. One thing I've been working on much more recently that seems to be extremely promising is something called dental calculus. Now, you probably know it by its other name, which is tartar. It's that stuff that you pay dentists to take off of your teeth when you go into your dental visits. What it effectively is is calcified dental plaque. And what's really amazing about it is that this calcification process—actually the mineralogic component of it is the same as in your bones and teeth. It fossilizes just like the rest of the skeleton and can preserve for millions of years. And this gives us ready access to the oral microbiome. So, I'm going to talk about the work that we've done so far on these two substrates. I'm going to begin with coprolites. Now, most of you probably don't know what coprolites look like, what paleofeces look like. So, I'm going to give you a couple of pictures. I've looked at a lot of coprolites now, and I can tell you that they're very diverse. So, human poop in the past looks—can look like a lot of things. They're different colors. They're different shapes. They're different sizes. One thing that is very common is they're often very fibrous, I have learned, by looking at them. The human diet in the past was a lot more fibrous than today. We often find whole pieces of plant preserved inside, whole seeds. These are coprolites from three different continents. So, on the top, this is a coprolite from Mexico. The one on the left is a coprolite from Austria, and the one on the right is a coprolite from Iran. But one of the problems we face immediate with coprolites is, as you might imagine, that feces decay and decompose really quickly. So, just because it looks well preserved to the naked eye, how well preserved is it really at a molecular level, at a DNA level? Well, a really clever man named Dan Knights came up with this program, which is fantastic. It uses Bayesian statistics to estimate or to quantify the preservation of thi9ngs like coprolites. And this is how it works; so, we can take a coprolite and we take DNA samples from it. And from that we can then compare them to potential sources. So, we can say, well, we think this coprolite might be a mixture of bacteria from the gut. And lots of people have studied the gut, so we have many, many sequences of DNA and bacteria from the gut in public databases. And we think it might also have some skin contamination; maybe some skin microbiome contamination from the archaeologists. So, we'll add into this. We'll add that as a possible source. We can also take things like soil. Lots of people study soil. There's millions and millions of DNA sequences from soil that have been deposited in databases. We can add that. And we can use this program. It takes the DNA that we've recovered from the coprolite and it tries to infer how much of each of those communities contributed to our coprolite. We can use this to authenticate it. We can apply this. So, these are two real coprolites from a real study that I'm doing right now. One's from Europe. One's from the Middle East. When we apply this method, what we find is actually it's incredibly well preserved. And that's because they're from salt mines, which turns out to be a really great preservational environment for coprolites. What we find here is that more than 50 percent of the bacteria that we can identify within these paleofeces are typical of the human gut microbiome. And so we now have a really good source of an ancient human gut microbiome. They date to the Iron Age. They're a little bit more than 1,500 years old. But as I mentioned before, the human gut microbiome is not monolithic. We see this big difference between traditional guts and industrialized guts. And so what we can actually do is we can split that gut microbiome component; that source component, and we can now ask what proportion of these ancient gut microbiomes—they're, like I said, about 1,500 years old. So, not all the way back to the Paleolithic. More recent than that. Do they look like these industrialized or traditional guts? When we apply—what we find actually is they look like traditional gut. And this is really interesting to me because these people were not subsistence farmers and they weren't hunter-gatherers. They come from the Celtic Empire. They come from the [Sassanid 27:48] Empire. These were miners in an ancient salt mine. And yet they look like these traditional guts. These ancient Europeans here look more like hunter-gatherers and subsistence farmers do today than they do like living Europeans in Europe right now. And that implies that there's been a tremendous change in the gut microbiome ecology over a very, very short time scale. Now, here I just have—we can go beyond using source tracker and just trying to associate with different communities. We can actually ask what types of bacteria are there. So, many of the genera that are found in the human gut microbiome are universal. We all have them. And here's what I call my A-list of fecal celebrities. These are the top fecal genera. And they're fantastic. We have Clostridium, Prevotella, [unintelligible 28:39], Coprococcus, Blautia, Roseburia. I guarantee every single one of you in this room has these bacteria in your gut right now digesting your dinner. These are the workhorses of the gut microbiome. But when we first got these results, there was one that really puzzled us because we weren't really sure how to interpret it. And that's this one here, which is Treponema. Now, most of you have probably never heard of Treponema. But if you have, what you've probably heard of is Treponema pallidum. That's the causative agent of syphilis. And Treponema denticola is the causative agent of periodontal disease. Treponema have a bad rap. There's a lot of pathogens in Treponema. There's spirochetes, spiral-shaped bacteria. And so we were really puzzled when we saw them in the human gut, and wondering what they were doing there. Now, this isn't syphilis. This isn't denticola. This isn't causing periodontal disease. It's a different type of Treponema, but what is it doing in the human gut? Because the Treponema is not thought to be part of the human gut microbiome. But then we realized that's because we were comparing to databases made up of sequences deposited from European and North American samples. And so we started to look a little more broadly. What we discovered is that Treponema is found in the gut microbiome of the great apes. It's also found in the gut microbiota of hunter-gatherers. And it's also found in the gut microbiome of traditional subsistence farmers. But where it is not found is in modern-day Europe or North America. So, this seems to be a group of bacteria that's been systematically lost from industrialized populations. What's interesting about this is that it's present both in hunter-gatherers and subsistence farmers in Africa, which is the cradle of humankind, and also in South America, which is the last human range expansion. And the fact that it's missing in the middle implies that this wasn't lost because it got lost along the way of traveling. It was lost probably because of our diets and our lifestyles. And so we're now following up this research. We've been able to take the data that we've obtained from this metagenomics soup that we obtained from fecal samples, and we've been able to determine there's at least 5 species of Treponemas found in humans that are no longer found in industrialized populations. We can analyze their genomes. We've actually used a computer algorithms to stitch these sequences back into reconstructed genomes. And we can tell that they're probably at least fiber digesters. They probably specialize in fiber digestion, and that's actually extremely interesting. So, bacteria that digests fiber, produce fatty acids as a by-product. And some of those fatty acids are very important. So, one fatty acid that's produced by some fiber digesters is called butyrate. And butyrates, it's actually the primary nutrient source for your colonocytes, the cells that line your colon. So, unlike many of your other cells, which are fed by nutrients that are traveling in your bloodstream, your colonocytes, your colon lining cells, they're actually fed directly from your gut from things like butyrate. And so these fiber-digesting bacteria are extremely important in feeding those cells. And so here we have what seems to be an entire clade of fiber-digesting bacteria that's been systematically lost from industrialized populations. And so we're following this up now, like I said. One thing we're also trying to do is grow them. We're trying to raise them in culture. This is exciting because when you discover a new bacteria, you get to name them. So, if anyone has any suggestions, see me after this. But this is a really exciting direction that we're now going. Okay, next I'm going to talk about dental calculus. I think it's an incredibly interesting and promising new area of research. Dental plaque was never so cool. Again, you probably don't know what it looks like, so here's a couple of images. And we have here a couple of archeological images and also an image of a living person. So, you can see what it looks like in a modern mouth. This is what happens if you never brush your teeth. So, feel free to show these images to your children if you need any help at night. Here's a good close up. This is a mandible. This is about 1,000 years old. It comes from a Medieval German cemetery. We can take a closer look at this tooth here. We're going to look at that dental calculus deposit. This is just a scanning electron microscopy image. We can look at it in cross section. I'm just going to zoom in on that calculus deposit right there. So, there it is again. We're going to zoom in again, and here we have it in cross section. And there's a number of really interesting things about it. First of all, you'll notice that it's layered. It seems to have this laminar structure. And that's because of how it forms. You first form a layer of dental plaque. It calcifies, and then you form another layer of dental plaque on top of it and so forth. And so it really builds up like tree rings or layers of an onion. And what's extraordinary about that—what's really exciting is that means this is actually a temporal record of this person's life. So, the interior layers are when they were younger. And this exterior layer was formed just before this particular woman died. And inside we have an ordered record of her life history fossilized in place. Incidentally, dental calculus is the only part of your body that actually fossilizes while you're still alive. And this is really important because it means it's protected from these post-mortem decomposition processes. Because it calcifies while you're alive, it doesn't actually decompose after you die. It's very resistant to decomposition, and so preserves for extraordinary amounts of time. Now, the oldest dental calculus that I know to exist comes from a fossil primate, and is 12 million years old. We can zoom in even closer, and here it becomes really apparent where this really shines. So, unlike a coprolites, which like I said are open systems, they can decompose. We're really at the mercy of chance that they just desiccate faster than decomposition can occur. Calculus is so different. What we see here, you can see individual microbial cells. These are the original oral microbial bacteria that have just been completely calcified. This white material here is calcium phosphate ions. It's been completely fossilized in place. All these bacteria are exactly where they were during life. And we can now decalcify this using a chemical that's the same chemical that's in your shampoo that gets rid of hard water. We use it on the teeth, and it removes the calcium and we're able to liberate this DNA. Now, one thing that's really extraordinary, too, about calculus, which I didn't know. This is something we discovered and was really exciting, is when we work with ancient samples they typically have very little DNA. And it makes it really hard to work with them. So, to put this in perspective, if we take dentin, for example, which is just the root of the tooth and you extract DNA from it, we get very little. So, the scale here, it's logarithmic. It's base 2. And it's the number of nanograms of DNA that we get per milligram of tissue that we analyze. And for something like dentin, it's really low. It's less than one nanogram of DNA per milligram. Coprolites have more DNA. They have on average about five nanograms of DNA per milligram of tissue. But calculus has an enormous quantity of DNA, in part because it's preserved so well. It has on average 40 nanograms of DNA per milligram of tissue that we can analyze. And the highest I've ever measured comes from a medieval sample in the U.K. It's this one on the far right. It had 506 nanograms of DNA per milligram of tissue. It was amazing. We saw messages on our machines we didn't know existed. Too much DNA, cannot measure. All right. So, if you're going to—please pardon my pun here, but I think we're only beginning to scratch the surface of what we can learn from dental calculus. But I'm going to show you some of the really exciting findings that we have so far. One thing that is really, really exciting—and I mentioned before that the trouble with coprolites is that they rarely preserve and we can't really predict where they're going to preserve or when. That's not true for calculus. So, calculus is found in every known living human population today. It's also found in every known archaeological population. We find it on Neanderthal teeth. We find it on Australopithecus teeth. And even chimpanzees make it quite abundant. So, here we have a record of the oral microbiome that spans the entire period of human evolution. So, I'm going to talk a little bit—this next part what I'm going to talk about is some work that we've published. It's primarily focusing on a German Medieval site, as I mentioned. And what can we find when we analyze calculus? Well, first of all, it's mostly bacteria. About 99 percent of it is bacterial. That makes sense. It's made of dental plaque. But about half a percent is eukaryotic. When we look at that, what we find is that is a combination of human DNA and dietary DNA. And I'll come back to that in a few minutes. We also find an abundance of proteins preserved within dental calculus. About 80 percent of them are bacterial, and about 20 percent of those are human. If we take those bacterial DNA sequences, though, that we've analyzed and we ask what we have, we have more than 2,000 different species we've identified. Most of them—about 85 percent—resolve to about 100 really common species. And some of them are extremely interesting. So, I mentioned before that the oral cavity is the natural reservoir for a large number of opportunistic pathogens. And so one thing we wanted to know was is that only true today, or what that also true in the past? And so we tested these medieval German samples for this. And what we found was a quite wide array of these opportunistic pathogens. Now, again, that doesn't mean they were necessarily infected with all of these diseases, but they carried the pathogens that have the potential to cause these diseases. We identified a large number of them. Just a few highlights are Streptococcus pnemoniae, which can cause pneumonia, Streptococcus pyogenes; that causes strep throat, Haemophilus influenza, that cause a variety of respiratory infections and Neisseria meningitides is one of the leading causes of meningitis. We also found bacteria associated with periodontal disease. There's three major ones that are associated with periodontal disease today. That's Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola. We found all three in these ancient samples, confirming that periodontal disease has the same etiology in the past as it does today. We then compared them to the frequency of these bacteria that we find healthy people today, and can confirm that our ancient individuals had very high levels of these bacteria. In one, the Tannerella forsythia, we actually had so many sequences from this that we were able to reconstruct its full genome. This was pretty exciting, so this is a full ancient human microbiome member that we were able to reconstruct. This pathogen has 14 known virulence factors. We identified all 14 in our ancient sample. One of these virulence factors, TFSB, it's a protein that the bacterium makes. It helps it evade the immune system. We actually also found it in our protein data. So, we not only had the gene that encoded the virulence factor, but we had the virulence factor itself. But one thing that really troubled us initially—we didn't quite know what to make of it—is we had this huge gap in our assembly. And this really bothered me because I felt like why is that DNA missing? Why can't we find that DNA? It's a large gap. It's 48,000 consecutive bases. It's 53 consecutive genes. And I really scratched my head over this on why we didn't have it until I realized what this is. It's something called a conjugative transposon. It is a mobile piece of DNA. It can move from species to species. And it encodes antibiotic resistance. And so what we found was that our ancient sample lacks it. It doesn't have it at all. This is something that is more recent. And that was really interesting. We also—although, we didn't find antibiotic resistance in this particular species—in this particular reconstruction—we did find many genes in this large metagenomics soup that have putative antibiotic resistance function. This is really interesting. This actually plays into how we understand how antibiotic resistance evolves. So, although we don't think that any of these ancient bacteria had a functional antibiotic resistance, many of the genes that are associated with antibiotic resistance today actually originally had different functions that had been repurposed for antibiotic resistance. And what this taught us is that the capacity for antibiotic resistance is very deep within the human microbiome. And so even if we could wipe out every strain today of functionally antibiotic resistant bacteria, they have the genetic machinery to regenerate it anew. And this goes very, very deep. All right. So, one thing that's super cool and really exciting about some of these ancient microbiomes is that in addition to learning about the microbiome itself, in addition to learning about these bacteria, calculus and coprolites also act as a kind of sync for other really interesting host and dietary information. So, I'm going to focus on the host. So, I mentioned before that we sometimes find human DNA—we find it in both calculus and we find it in coprolites. And so one thing we wanted to know was is it enough to do something interesting with? And so we started playing around with it, and we found that we can actually now reconstruct full mitochondrial genomes just from the DNA that got left over inside dental calculus and coprolites. This is fantastic because we can use mitochondrial genomes to then infer ancestry and also large migration events. We find a lot of human proteins in dental calculus. But one thing that really fascinated me was that when I started analyzing them I realized this is just a protein interaction where each dot is a different protein. I've color-coded it by what the protein does, what basic function is. And red is the innate immune system. We saw a lot of immune proteins in calculus. What we're actually seeing—this is amazing. We're not only seeing pathogens that are in there, periodontal pathogens that are causing disease virulence factors, we can actually see the host immune response to that ancient infection. We have a complete infectious reaction that we can see entrapped in these ancient calculus samples. We also have really interesting information about diet. We now have a direct source. We can go into the past and interrogate various aspects of people's diet. So, in dental calculus, one thing we find is we sometimes find little bits—little micro fossils that are visible under the microscope of people's diets. So, as you know, sometimes food gets stuck in your teeth. And that happened in the past as well. And thousands of years later we can use a microscope and identify it. So, this particular Medieval German had a variety of things stuck in their teeth. They had a little bit of connective tissue from some meat that they had been eating. They had some plant [unintelligible 43:10]. And they had a couple of starch granules, which we see here on the bottom. This goes to the fact that plaque can sometimes calcify so quickly that even little starch granules that you've eaten in your diet can become entrapped and preserved over thousands of years. This one on the left is consistent with wheat. And the one on the right is very similar to what we see in peas. We can also take DNA out of these samples and look for specific dietary DNA signatures. And from this sample, we were able to identify four different food stuffs. We were able to identify sheep, pigs, cabbage and wheat. Not particularly surprising for a Medieval German diet, but a great proof of principle that we were on the right track. But what's also interesting is that we can start to get at another question. So, I'm very interested in the origins of diary. As many of you know, one of the tenets of the Paleo Diet is that you shouldn't eat diary. And diary is a really odd thing. We are the only mammals on earth that continue to drink milk long after our infancy. And that is very strange. But diary on a global scale is big business. The global milk production today is 697 million metric tons per year of milk. That is huge.
I don't know about you, but I have a hard time visualizing what millions of metric tons are, so I converted these units into things that are a little bit easier to understand. So, 697 million metric tons is the same as 278,800 Olympic-sized swimming pools, or 217 Walden Ponds of milk are produced every year on this planet. And this is fascinating to me because this is enough for every single person on earth every day to consume a quarter liter of milk. And, yet, the vast majority of the world's population is lactose intolerant. So, how did we come to this position where we have—where diary is so widespread and, yet, most people can't consume milk as adults? And it turns out that dental calculus can help us understand this. Because one of the proteins that we started finding over and over again in these ancient samples when we combed through the proteins that we got out was something called [beta lactam globulin 45:29]. Beta lactam globulin is a protein that is specific to milk. What's also interesting is humans don't make it. We actually have a defect in this gene, so we don't produce it. But it's produced by all of the diary livestock that we use today. And so what we can do is we can go to dental calculus of particular populations in the past, we can measure their calculus. We can recover this protein, and we can infer who was drinking milk at a personal level throughout prehistory. And so we've done this. So, we went and we got 100 dental calculus samples from across Europe, spanning more than 4,000 years, and we were able to type who was drinking milk where and when. And using this information, we were able to say, for example, that Bronze Age northern Italians liked goat milk because there are mutations that actually indicate the species. And we could also say that people living in Rome and Britain preferred sheep and cattle milk. The Norse Vikings really liked their cattle milk. And so we can start to go back and reconstruct this history of diary. We've now expanded this project, and we're focusing now on the Neolithic and trying to push it back even further in the near East and in Europe and trying to track the spread of milk across the continent. This is exciting to me because milk is otherwise extremely difficult to study, as you might imagine. It does not preserve well in the archeological record. We don't actually know when people started diary. And so this is a new area of research for us. And so I hope I've convinced you that studying the microbiome is incredibly interesting and also valuable and that we can do this by both studying diverse people today and also by directing going into the past and studying these preserved microbiome substrates. By putting all this information together, we can start to gain a much better appreciation of our complete selves, so not only our own evolution, but the evolution of the trillions of microbes that call us home. Thank you very much. And I want to acknowledge all of these wonderful people who helped with this research. Speaker: A huge tank you to Dr. Warinner. We will now be taking some questions from you. There'll be two roaming mics going around. And, Christina, I'm going to start right over here. Question: If I heard you right, obese people are missing certain microbes. And if that's so, why not bottle these missing microbes and give it to the obese people to help them out? Warinner: This is a great question. So, the question is if we're missing microbes, could we just bottle them and give them to people who are lacking them? It's a fantastic question. So, this is the whole question behind probiotics and whether or not probiotics are useful. I think our research has started to circle around on the fact that this could be really important. We still have some ways to go here in terms of the Treponema, for example, we don't completely know their function. We're inferring it from the genomic sequences that we have. The next step is we have to actually grow them in the lab and show what they do, prove that. There are some challenges in delivery. How do you transmit microbes, so that they survive through the entire gastrointestinal tract? Will they colonize? One thing that's a little bit tricky is that we seem highly receptive to accepting microbes for the first three years of life. But after that, it's actually quite difficult for us to acquire new microbes. There's actually some really interesting studies that have been done looking at kissing and to what degree microbes are transmitted through kissing. And it turns out you have to kiss for a really, really long time and really, really intensely to transfer your microbes to another person for an extended period. So, there seems to be a window there. But I agree. I think there's a tremendous potential for transferring these microbes. And where this has been already demonstrated to be very effective is people who have Clostridium difficile infections. These are people who have often been on a very long and intensive course of antibiotics and it's killed most of their gut microbiome. Clostridium difficile is a type of bacteria that's naturally highly resistant to antibiotics, and it tends to survive, and then over-colonize causing severe diarrhea. These people have been very effectively treated through fecal transplants. So, the transplantation of healthy microbes from a healthy individual into these individuals. So, I think there's tremendous potential for the sort of probiotic approach. Yes? Question: Hi. I feel like the microbiome is this tricky moment where people are aware of it and don't really know what to make of it. And, therefore, [unintelligible 50:24] enterprises are popping up [unintelligible]. So, I'm just curious [unintelligible] some of these. I know there's some companies that offer [unintelligible] microbiome. I'm curious about how reliable those results are. And also all the various ways in which probiotics are being offered to the public. I'm curious if you think those are legitimate or if they're just people throwing money at something. Warinner: Well, I have to admit it's a little bit of a Wild West out there. Probiotics are not regulated very much. Well, they are and they're not. So, the probiotics that are available today are generally probiotics that fall under the grass category; the generally recognized as safe. So, if something has already been in the food chain for a certain number of years, they don't have to undergo new regulatory approvals to get it in there, which is why most of the probiotics that are available today are bacteria or fungi that are traditionally used in foods. So, they're diary bacteria or bacteria used in making sauerkraut or bacteria used in making beer or wine. Those are very available because they're known to be safe. They're not necessarily the best probiotics for you. I mean, really the better probiotic for you would be human associated bacteria because those are really very different. They don't colonize the human body very well. But the regulatory hurdles for getting those approved are very difficult. In terms of the different companies, I can't speak to the accuracy of their reconstructions. They're not really regulated at this point. I can say, though, with probiotics one problem is there's no—they're not required to prove the probiotics are actually alive. So, a lot of probiotics that you might buy are actually dead. There's no guarantee on that. So, it is really a Wild West out there, I have to admit. So, buyer beware if you're interested in those things. Speaker: We have another question all the way on your right over here. On your right. Question: Hi. I read that babies who are born through C-section have less bacteria in their system. And I was wondering if you considered that or studying that when you compared America to the other civilizations? Warinner: That's a fascinating question. So, I have not personally done research on this, but I think this entire area is really interesting. So, the question is to what degree does the mode of birth affect your microbiome? And there are a number of studies that have looked at this, and the results I think are fascinating. So, when a baby is born a fetus—it's unclear if they're completely sterile or they might have a small amount of bacteria, but either way they have very little. When they're born—when they pass through the birth canal—they pick up a massive amount of vaginal bacteria. And this is the—this seeds their microbiome. What's really interesting is that that's the dominant—those are the dominant bacteria that they have for some time, for up to three years of life before they start developing their mature microbiome. So, for a young infant, if you swab them almost anywhere on their body, they're going to look like the vaginal microbiome. And that's really important because vaginal bacteria include lactobacilli, which can break down lactose and aid the baby in digesting its food. Now, more than 30 percent of babies today are born by C-section, which means they're not exposed to these vaginal microbes. And in fact their first major microbial exposure is through skin microbiome by being held or being nursed. And so they have a completely different microbial exposure. And as a result, they have a completely different consortia of microbes that initially colonize them. And so for up to three years of life, you can swab a baby and determine whether or not it was born naturally or by C-section because of these very distinct communities. And now it's thought that this impacts the maturation of the microbiome and, therefore, has long-term effects on the immune system development in particular. So, there are a different set of studies that have looked statistically at the relationship between C-section birth and allergy risk. And there is a correlation between higher allergy risks with C-section birth than with natural birth. But this is a slightly elevated risk. It's not entirely predictive. There's a lot of overlap here. But I think this is really fascinating. There's actually a series of clinical trials that are going on right now. And we won't have the results for a little while, but I think it's really fascinating. This is going on in Puerto Rico where they are taking women who are having C-sections and they're taking vaginal swabs and using that to inoculate the infant to see if they con confer this protective effect and seed the baby who is being born by C-section with these vaginal microbes. Speaker: Got one right in front here. Yeah? Question: In your talk today you have discussed food that's naturally produced. And my question refers to junk food or food that's been corrupted with chemicals and artificial production. Warinner: Yeah. And what effect that might have? So, yes, the question is—so, I talked a lot about natural foods. And what do artificial foods or junk foods—what impact does that have? And I think this is a really fascinating question. It gets to some of the really deep, underlying questions of this entire endeavor. So, one of the things is that today with modern food technology we are able to pull apart foods and reconstitute them in ways that were never possible in the past. We can increase the amount of sugar or the amount of fat in a food to levels that would have been impossible to eat in a natural food. And that raises a lot of questions. And I think one of the things that we're homing in on is one question we have is why do we see lower diversity in these industrialized environments? What's the cause? One thing you have to remember is these microbes need food, too, and what food gets to the microbes? So, our bodies are able to digest anything that's very simple. So, if it's a simple sugar, we can digest that and we absorb those nutrients right away. If it's a simple starch, same thing. If it's a simple protein or a simple fat, again, we can absorb all of those nutrients. What goes to your colon—what actually goes to your gut microbiome are all those things that you can't digest; all the fiber, the soluble fiber, the insoluble fiber. That's actually the food for your microbes. And as we eat increasingly refined and processed foods, it has less and less of that fiber; less and less of those components that were a part of our traditional diets that are no longer getting to those microbes. And I think essentially they're starving to death. They just don't have any food. We're weeding them out because we aren't feeding them. Now, one thing that is really interesting to me—and this was only very recently recognized, is some recent research on breast milk. Because we thought we understood what breast milk is about. It's about giving energy to the infant and it has lactose, sugar and it has proteins and it has fats. But it turns out that the carbohydrate component of breast milk is actually extremely complex. And there are lots of sugars that are specifically produced in human breast milk that babies can't digest. Now, this is very energetically costly to the mother. Why would a mother produce a bunch of sugars to feed to a baby who actually can't digest them? And it turns out it's actually not food for the baby at all. It's food for their microbes. It's food for specific types of microbes that promote health in the baby, assist with digestion and promote maturation of the immune system. So, I think this is a really interesting and important question. How does our diet influence our microbes? And actually from what we know now, it's to an extreme degree. It's very, very important. I think it's a great question. Another question we get asked is to what—we also have in our modern foods today because we want them to have long shelf lives because that helps with the cost effectiveness of preparing foods. But the reason these foods have long shelf lives is often because they have bacteria static or anti-microbial compounds in those. How do those affect our gut microbiome? How does that affect our microbes? We actually don't have an answer to that. Speaker: So, we have time for a couple more questions. And, Christina, there's a question for you all the way in the back. You won't even be able to see us, so just keep your ears open. Warinner: Okay. Question: Actually I have two questions. First of all, when did the culling of the number of bacteria take place in modern populations? And, second of all, do we have any evidence of Neanderthal gut bacteria coming into modern populations when we interbred? Warinner: Those are great questions. The problem is we don't have enough coprolites. So, the samples that I showed you here—so, I identified three sites where we have what I call functional coprolites, meaning they have really well preserved DNA that reflects an authentic gut microbiome. Those are the only three I have ever found. And we have looked at a lot of sites. We don't have any coprolites from Neanderthals that are preserved. So, I can't say anything about that unfortunately. In terms of when these changes really started occurring, until we find more coprolites it's going to be very hard to narrow down the exact timeframe. But we are starting to do that. What I'm also hoping is by also incorporating calculus research, which as I said we're really at the beginning of this, calculus preserves much better. And we might be able to use it as a proxy for some of these changes. But this is very early, and we're still exploring it. But we're always on the hunt for a new coprolites. So, if any of you find any new coprolites, or if you hear of any new coprolites, I'm happy to test them. That's really our limitation at this point, is finding the right material to study. Speaker: Right in front here. Question: I understand that if you have pets early that you have fewer allergies. And I also heard that you share your biome with your pet. Is that true? Warinner: Yeah. There's some overlap. This is really interesting. So, it has been shown that statistically people that grow up with pets or in proximity to livestock have lower rates of allergies, eczema and asthma. They have lower rates of atopic diseases. It seems that this early life exposure to harmless bacteria and specifically peptidoglycan and other components of the bacterial cell wall is very important in helping the immune system to mature and shifting the balance of the immune cells towards bacteria that react to bacteria and away from immune cells that are more involved in things like allergic response. So, having these early life exposures seems to be protective and associated with fewer allergies and atopic diseases later on. And you had a second part of your question. Yes, and so do you share these microbes? Yes. So, there have been a number of studies that are really interesting where they have looked at people and their dogs. And they do share some microbes, which I find really interesting because in the kissing study you had to really, really get up in there in order to share your microbes. So, it makes me wonder what's going on in these homes. But, yes, people who have dogs do tend to share some microbes with their dogs. Now, one thing that was also really, really interesting—this was a study that came out a couple of years ago. And they were looking at the air microbiome. They wanted to know what kinds of bacteria were ambiantly in the air. And they looked at both—I think this was in Detroit. And they were looking in the summer, and they were looking in the winter. In the summer, they found what you might expect; a lot of microbes associated with soil and with leaves and with trees and the natural environment. Lovely and wonderful. And then they looked at the winter time, and what they found was dog gut microbiome. So, what they realized was happening was in the winter time there's not much living going on. All the trees are dormant. Everything's covered in snow. But what is readily available and steaming and producing aerosols directly into the air is dog poop all over the city. So, the air was dominated by—I mean, in absolute numbers it was still low, but still. That the dominant bacteria in the air in the winter was dog poop. So, yes, we do share microbes with our pets. We are continuously exposed. Speaker: And we have our last question right over here in the center. Question: It's interesting the last question relates to mine. When talking about the differences in microbiomes between hunter-gatherer, agricultural and industrial populations you really focused a lot on food. Do you think the concentration of population and the environment that we're in also has as much of an effect on your gut microbiome? Warinner: That's a fantastic question. Yes, I think it does. One thing I've been really interested in—and we've been trying to think of ways of studying this—is transmission. I think this raises a great question. How do we transmit our microbiome? How do we give—I mean, koalas do it through pap. But how do we give our microbiome to our offspring? And how does hygiene affect this, for example? This is, I think, absolutely fascinating. And I think this might also contribute to why we have lower diversity in urban industrialized societies. I think we have impaired transmission of our microbiome. When you're living in a more traditional society, the built environment is less sterile. You're more in contact with each other. You have larger families. There's more siblings that are transmitting microbiomes back and forth. When we have smaller family sizes, we're living in urban-built environments that are quite sterile and abiotic. I think we have limited transfer, especially when we have lots of hygiene and cleaning. And this could be impairing this transmission. It could be a major factor behind the loss of these claves that we see in urban industrialized populations. Speaker: So, please join me again thanking Dr. Warinner. Narrator: Thanks for listening to Public Programs at the American Museum of Natural History. To listen to our archive of podcasts, visit amnh.org/podcasts. The SciCafe Series is proudly sponsored by Judy and Josh Weston. This SciCafe event is presented in collaboration with The Leakey Foundation. SciCafe: How "Paleo" is Your Diet?, The Secret World Inside You, and related activities are generously supported by the Science Education Partnership Award (SEPA) program of the National Institutes of Health (NIH).