- Links We Discuss
- Just How Many Microbial Cells Are There?
- What Are the Primary Functions of the Microbiota?
- The Connection between Microbiota and Chronic Disease
- How Do You Define a Healthy Microbiota?
- The Connection between Low Microbial Diversity and Disease
- Can We Manipulate Our Microbiota?
- What Inspired You to Write Your Book?
In this episode, we cover:
03:25 Just how many microbial cells are there?
11:38 What are the primary functions of the microbiota?
15:59 The connection between microbiota and chronic disease
27:14 How do you define a healthy microbiota?
30:36 The connection between low microbial diversity and disease
35:24 Can we manipulate our microbiota?
39:40 What inspired you to write your book?
Links We Discuss
- The Good Gut: Taking Control of Your Weight, Your Mood, and Your Long-term Health by Justin and Erica Sonnenburg
Chris Kresser: I’m Chris Kresser and this is Revolution Health Radio.
Hey, everybody, it’s Chris Kresser. Welcome to another episode of Revolution Health Radio.
Today I’m really excited to welcome Justin Sonnenburg as my guest. He is currently an associate professor in the Department of Microbiology and Immunology at the Stanford School of Medicine. He conducted his PhD in biomedical sciences at the University of California, San Diego, in the laboratory of Ajit Varki. His postdoctoral work was conducted at Washington University in Saint Louis, Missouri, in the laboratory of Jeffrey Gordon. After moving to Stanford University in 2008, Justin received an NIH Director’s New Innovator Award. In 2011 he received the Burroughs Wellcome Fund Investigators in Pathogenesis of Infectious Disease Award. He and his wife and collaborator, Erica Sonnenburg, PhD, are the authors of the book The Good Gut: Taking Control of Your Weight, Your Mood, and Your Long-Term Health. The goals of the Sonnenburg Lab are to elucidate the basic mechanisms that underlie dynamics within the gut microbiota and to devise and implement strategies to prevent and treat disease in humans via the gut microbiota. The long-term objective of the research program is to continue to the emerging vision of how our microbiota may be incorporated into precision medicine.
I met Justin at the UCSF Paleo event a couple of months ago and was really impressed with the presentation and talk he gave. I’ve read his book, which I enjoyed, and I’ve been familiar with his work for some time, so I wanted to invite him onto the show to discuss the latest research on the microbiota and its connection to health and disease and harvest some clinical pearls for what we can do to improve our microbiota and our overall health. Without further ado, let’s dive in.
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OK, now back to the show.
Chris Kresser: Justin, thanks so much for taking the time to do this. It’s a pleasure to have you.
Justin Sonnenburg, PhD: It’s great to be with you.
Just How Many Microbial Cells Are There?
Chris Kresser: When I first met you, it was at the UCSF Symposium where you did a talk on some of your research on the microbiome. Before we dive into some of the specifics there, I think it would be interesting just to kind of get a state of the union, the latest microbiome research from a general perspective. My listeners are very familiar with the microbiome, I’ve been talking about it for years, but there was an interesting paper—I think it was published in Nature; correct me if I’m wrong—that contradicted this long-held idea that there’s a 10:1 ratio of microbial cells to human cells in the body, which I think I put in my book a few years ago. It was kind of the dominant idea at that point. And this recent paper suggested that that ratio is maybe more like 1:1 or 1.3:1. So I guess my question is, that’s interesting. Does it matter? Does it change the way that we’re looking at this at all? What are your thoughts on that?
Justin Sonnenburg, PhD: Yeah, sure. That was a nice paper just to kind of start a discussion about this, and it actually was published in Cell.
Chris Kresser: Right.
Justin Sonnenburg, PhD: And they revisited some of the traditional literature on which the early estimates were based and I think a lot of the recent numbers that have been cited came from, and then they have gone back through the literature, more recent literature, and detailed a more thorough accounting of cells on both the host and microbial sides to come to this number of 1.3:1.
I think it highlights a few things. The first thing is counting is difficult in science, and it’s a little bit, maybe, counterintuitive, but particularly when you’re dealing with these microbes that are so incredibly small in places that are hard to see, with incredible dynamics over time and probably tremendous variability from individual to individual in terms of densities across populations, it’s kind of hard to distill this down into just one number. I think the original number of 10:1, that we’re more bacterial or more microbial than we are human, was just a back-of-the-envelope calculation, and it never really was meant to be something as real quantitative, but it gave us just kind of this new kind of perspective that we do harbor a lot of microbial cells.
The more recent number of 1.3:1, there are a few things to note there. There were revisions on both sides. The microbes got a little less abundant, and the human cells got a little more abundant, but in this revision, they counted our red blood cells, which, by far, are the most numerous type of cell in our body, making up over 80 percent of the cells in the human body. Now, these cells aren’t even really considered cells by a lot of biologists just because they don’t have a nucleus and they don’t conduct a lot of the same biology and signalling that normal other cells, nucleated cells, do. So if you get rid of those cells, we’re back to a 10:1 ratio.
Chris Kresser: Interesting.
Justin Sonnenburg, PhD: I think it’s important to come to more accurate numbers over time in science, I think it’s important to pay attention to this kind of developing line of inquiry, but it doesn’t change the fact that we have this tremendous number of microbes that inhabit the human body, and they have a really tremendous impact on our biology, which is probably the most important part, even if it was only five cells and they had the impact that they do, we would still want to study the heck out of them and understand them really well, and that’s really the important part.
Chris Kresser: Right. We can’t get too hung up on these particular numbers, as fascinating as they are. Did that revision in the estimate of the ratio of cells affect the estimates in terms of the genome? The estimate I’ve seen a lot is that there are 100 times more genes in the microbiome than there are in the human genome.
Justin Sonnenburg, PhD: Right. That number is interesting, and it really depends on the way that you look at that number. A lot of people throw that number out there, and I think a major question is, does that refer to the collective microbiome across the whole planet in terms of the number of microbial genes that could be in the gut, or is it for a single person?
Chris Kresser: Right.
Justin Sonnenburg, PhD: That’s really important. And if you’re considering all the microbial genes that are out there as one of the factors in this ratio, that’s going to grow with time because as we survey more and more microbiomes across the planet, we’ll discover more and more genes. And even if we were just studying a single microbiome, the estimate would go up over time just because sequencing technology gets better and our computational algorithms for detecting these genes gets better. So that number will continue to increase over time as we’re able to delineate more and more gene families. This probably had a slight downward effect on that just because of the downward revision on microbes, but on the one hand, cell number is not equivalent to the species makeup of the gut microbiota, so you could have a species there at 10 times the abundance in one person than another, and it doesn’t change the collective genome that’s there because that microbe has the same genome, so it’s probably not that big of an effect.
Chris Kresser: Right. There’s a quote that I came across a while back that I think was attributed to you, and I’m going to just paraphrase it, but it’s something along the lines of, “Humans are basically elaborate vessels for the propagation of microorganisms.”
Justin Sonnenburg, PhD: Yeah, that’s good! Actually I stole that from somebody named Dwayne Savage who’s one of a previous generation of scientists that really established the foundation for this field. I think it really puts into context that the microbes are holding the reins to a lot of what’s going on. If we were not doing a good job at passaging them around to additional culturing flasks—specifically, other humans—they would undoubtedly discover ways to make us better at doing that.
Humans are basically elaborate vessels for the propagation of microorganisms.
I think a more optimistic or different way to frame this is just that we’re composite organisms, that we, I think, traditionally think of ourselves, the human body, as a collection of human cells, and what we really are is an ecosystem. We have microbial and human parts that come together to work in a concerted fashion to make us this superorganism, and we can’t forget about the microbes because they’re really an important part of our biology.
Chris Kresser: Yes. Right now we’re just laying the groundwork, and that’s exactly what I wanted to do to start. I think it’s really important to have that context because up until very recently, all of the discussion around what kind of diet is appropriate and other kinds of environmental and lifestyle interventions have all centered around their effect on the human host and not necessarily on their effect on microbes, and as you talk about in your book, which we’re going to come back to later, and also in the presentation that I watched you give, one of the things I’ve been arguing is for every bite of food that we put in our mouth—or anything that we put in our mouth, not just food; we could talk about antibiotics and other things that influence the microbiome—we should consider how it affects us, the human host, and also the microbiome.
Justin Sonnenburg, PhD: Yeah, that’s very well stated. If you look at everything from dietary guidelines to just kind of commonsense advice and what we try to think about in terms of nutrition for people that concentrate on this, I think the microbes just haven’t been a part of the conversation up until very recently. That really needs to change because I think our appreciation of this microbial community has come to the point where we understand that, exactly what you said, what we put in our mouth is what is driving what this community is doing and, therefore, influencing health and disease. So that’s something that we just need to think about and try to make a bigger part of the conversation.
What Are the Primary Functions of the Microbiota?
Chris Kresser: Mm-hmm. So let’s say you’re at a cocktail party and you meet someone and they have absolutely no idea… maybe they’ve been living in a cave and they haven’t heard the word “microbiome!”
Justin Sonnenburg, PhD: Yeah.
Chris Kresser: It’s really in the popular media now, but let’s say they’ve never heard of the microbiome and they’ve never really thought about this stuff at all. How would you explain to them, in a sort of cocktail-party way, what the functions of the microbiota are? What’s the main role that it plays or the main roles that it plays?
Justin Sonnenburg, PhD: Just to make sure that the lingo is straight because I have different words that will wind in as I’m talking and I want people to understand, I think traditionally scientists in this field talked about the community of microbes as the “microbiota” and then their collective genome is the “microbiome,” but there has been an evolution in the terminology to where a lot of people, particularly nonscientists, refer to this community as the “microbiome,” and part of that was fueled by NIH, National Institutes of Health, using that term in their Human Microbiome Project, this five-year project to perform a lot of sequencing and kind of lay a foundation for this field. So I kind of use the two interchangeably now, but I might use “microbiota,” which just means the community.
Chris Kresser: Right.
Justin Sonnenburg, PhD: I think, for people that haven’t, up to this point, been paying a lot of attention to these microbes, it’s important to note that probably the major function of this community that we’ve known for decades and which has held up over time, even in the face of all this technological innovation in studying this community, is that the microbes in our gut mainly live in the colon, in the distal part of the digestive tract, and therefore really only have access to items that we eat that are poorly digested by our own digestive enzymes and are poorly absorbed in our small intestine, so this is primarily dietary fiber, the complex carbohydrates that are found in plant material. This is what escapes our own digestion in the upper portions of our digestive tract, makes their way to the colon, and then are consumed and serve as the primary fuel for driving the metabolism of the microbiota. Digestion of these complex dietary fibers is probably one of the major functions that is attributed to and been proven to be really important for this community.
An extension of that is the importance of these microbes in gut health. We know that these microbes can make us feel good or bad in terms of digestive health. Bloating can be an issue. We know that inflammatory bowel disease can be driven by these microbes, so there has always been an appreciation that the microbes in our gut play a role in gut health.
I think what has really been startling to many of us in this field and certainly people outside the field is just how much of our biology outside of the gut is being controlled by these microbes. We know that metabolism that’s going on all over our body—for instance, in our liver—is directly affected by what’s going on in our gut microbiota. We know that our brain can be affected by chemical signals that these microbes secrete into the bloodstream or get absorbed into our bloodstream and then circulate through our body. So really the gut microbiota, I think, can be thought of as a control center for so much of our biology, and by far, I would say, to this point, the most important facet of our biology that’s impacted by this microbial community is our immune function, again, certainly in the intestine, but throughout our body, how likely we are to fight off a respiratory infection, how quickly an autoimmune disease in our central nervous system progresses, how we respond to vaccination, all of these things are impacted by what our gut microbes are doing. That means that because the gut microbiota is malleable, because it changes day to day and we can affect it through what we eat, that means we have an incredible lever on many aspects of our biology, including how our immune system functions.
The Connection between Microbiota and Chronic Disease
Chris Kresser: Mm-hmm. I just want to excerpt something you said because it struck me when you were doing this presentation. It was on one of your slides, and you just mentioned it now, which is this idea of the microbiota as a control center for human biology. I think if you were to give just a one-sentence explanation, that would really encapsulate what we’re talking about here because it’s not just impacting digestion and absorption, as you said, which we’ve known about for a long time, but it’s having these systemic impacts on the immune system and metabolism. Also brain chemistry, we know the microbiota has a pretty profound effect on, mood and behavioral dysfunction, and what this means, if you’re just a regular person or if you’re a clinician, is if a patient comes in to see me and they have a tendency to get a lot of colds and flus and they have maybe some mood disorder or anxiety and maybe they’re overweight and insulin resistant, the first thing I’m going to be thinking of is the gut, whereas maybe that might not make a lot of sense to someone in the general public. When you embrace this concept of the microbiota as a control center, you start to see the potential for how we can intervene with these chronic diseases.
Justin Sonnenburg, PhD: Yeah, I think that’s excellent. You mentioned chronic diseases, and I think that there’s a major connection between what’s going on in our gut microbiota and inflammation, which occurs at various sites throughout our body. We know that it’s inflammation that drives many of these chronic diseases, and so that’s probably a really fundamental important connection.
Chris Kresser: Let’s talk a little bit more about that. Another thing that struck me from your talk was just this concept of the microbiota as a mediator or a mechanism that is behind much of the modern disease epidemic. That doesn’t mean it’s even the root cause. The causes might be more proximal things, like our diet and not sleeping enough and excess use of antibiotics and an overly sanitary environment and all these things, but the way, the mechanism by which those causes lead to disease may be the microbiota in many cases.
Justin Sonnenburg, PhD: Yeah, that’s wonderfully stated, Chris. I think we don’t want to overhype the microbiota as being the root cause of every malady that we’re experiencing.
Chris Kresser: Right.
Justin Sonnenburg, PhD: But I think of reframing it as a moderator of many of these effects is incredibly important. Probably a good example of that is obesity. There’s been just a tremendous body of literature generated over the past decade connecting gut microbes to obesity and metabolic diseases. It’s very clear that you can take the microbiota from an obese mouse and put it into a healthy, lean mouse, and that lean mouse that receives just that microbiota, eating the same exact thing that he was eating before, will start increasing weight more rapidly, gaining weight, and start exhibiting some of the metabolic derangements from the donor animal. These were really profound findings in the field. They are very solid and have held up in a variety of labs and a variety of instances, but I think that going back to your point about the root cause, I don’t think anybody would argue that in the vast majority of cases it’s what people are choosing to eat that’s driving obesity, but then clearly there’s this really important part that the microbiota is playing in the propagation of these diseases. That’s one example.
These Western diseases are noncommunicable. Chronic diseases, in general, are interesting because we call them Western diseases because we see them in industrialized countries. We see the vast majority of these, the trends are going up in synchrony. They’re just rising in prevalence, and there are dozens of them. It ranges from heart disease to autoimmune diseases like allergies, asthma, multiple sclerosis, many cancers, the metabolic diseases, as we were just talking about, and one possibility is that there are dozens of different things that are contributing to all of these diseases, but I think a much more likely explanation is there’s a handful, maybe just a few, major issues with how we’re living our Western life that are really driving a lot of this disease, and I think there are a lot of arrows pointing to how diet has impacted the microbiota and potentially other factors in Western life, like antibiotics and sanitation and so forth, many of which have had really great benefits to society, but at the same time have had collateral damage to the gut microbiota very likely, which may be playing an incredible role in many of these Western diseases.
And we can talk more about the studies of traditional populations microbiota if you want to, but there’s very good evidence now that the Western microbiota—the microbiota of Americans, in general—is very different than it was very recently in evolutionary history and that we’ve actually lost species, lost diversity, and that our microbiota has somewhat deteriorated.
Chris Kresser: Right. This is such a rich topic of conversation, and there are so many ways we can go. I do want to just point out something that you said that I think is so important for people to get. As a health educator and a clinician, I’m interested in finding simple ways to talk about things that aren’t oversimplified and overly reductionistic, and one of the kind of formulas that I talk about is if we think of what is the root cause of most modern disease, we could say it’s a combination of genetic predisposition plus modern environment, and then maybe one of the primary mediators of that that determines what disease we get, because not everyone gets the same disease—one person gets type 2 diabetes, another person gets eczema, another person gets autoimmune disease—and maybe what that is genetics and epigenetics and the microbiota and the genome, the microbiome.
Justin Sonnenburg, PhD: Right. Yeah, I think a really important part of this is there’s a really nice developing body of literature that shows that the gut microbiota, actually if it’s fed dietary fiber, something that’s greatly deficient in the Western diet, and then ferments that fiber and creates chemicals known as short-chain fatty acids—that’s the fermentation endproducts of what the microbiota is doing to fiber—those get absorbed into our circulation and have apparent antiinflammatory effects. That means that if we’re not eating fiber, our microbiota is not producing as many short-chain fatty acids, and we don’t have the same level of anti-inflammatory compounds floating around in our bloodstream. One of the really common denominators of these chronic Western diseases is inflammation. It’s really decades of inflammation that sets us up to get one of these diseases, and then it’s inflammation that drives it. You can think about something like arthritis or inflammatory bowel disease, perhaps. There are many diseases like this that are just driven by inflammation.
I think the idea of epigenetics and human genetics, our own genetic uniqueness as a person, probably is what is determining whether we get heart disease, allergies, eczema, or something else, multiple sclerosis, for instance. I think that these are all normal human genetic variation overlaid on this inflammatory state that is being created by multiple factors, but probably diet-microbiota interaction is a major contributor.
Chris Kresser: Yes. The reason I think this is so important is because that’s not really what has been communicated over the past few decades. In conventional medicine, there’s a doctor for each different body part, and so if you have heart disease and you have eczema, you go see the cardiologist for heart disease, you see the dermatologist for eczema, maybe you see an immunologist if you have an autoimmune disease, and all of these things are being looked at as separate conditions. As a patient, it can be pretty bewildering to just have this idea that you have all of these kind of separate and disconnected things happening and not to have an idea that there might be a common root cause that’s driving all of these pathologies. Of course, what that means is if there is a common root cause, then there’s a possibility of intervening at that level and seeing an improvement across the board in all of these conditions instead of trying to address each of them in a kind of silo fashion with specific drugs and things for each condition.
Justin Sonnenburg, PhD: Yeah, I think it’s a great point. One of the scary directions—and ultimately it may be useful in some instances—is to watch as this field of research focused around the microbiota goes further down the track of traditional drug discovery, trying to find molecules that can target the microbiota and try to knock out some problematic function. When you’re dealing with a complex microbial ecosystem, it’s just so incredibly difficult to find something that will be both generalizable across many people, or at least across a big enough category of people that it’s worthwhile to develop, and then also will give you the desired or predicted outcome. I think that this idea that there are probably some very simple answers to this really complex system, that we maybe can get 80 percent of the way there by just applying general rules and then focus on the remaining 20 percent that will be individualized and recalcitrant to these very generalized methods forward, I think that that would be a really productive way to look at this.
Actually we’ve recently started the Center for Human Microbiome Studies at Stanford. I’m co-director with somebody named David Relman, a pioneer of this field, and I think one of our big hopes with that center is to focus human studies in a direction that will allow us to gain insight into how we can modify lifestyle practices, diet, and medical practices in a way that protects and restores this microbial community, to try to get us up to that 80-or-so percent of just general rule, reaping the benefit from that, and then turn our attention to these more specialized things that will require personalized approaches.
How Do You Define a Healthy Microbiota?
Chris Kresser: Mm-hmm. OK, so let’s get back to a little bit more of the specifics on the microbiota. So far in this interview and also just in general, there’s been a lot of discussion on the importance of a healthy microbiota, but do we know what that is yet? You’ve already hinted that it may not be the same for you and I as it is for a Hadza hunter-gatherer, for example.
Justin Sonnenburg, PhD: Yeah, it’s a very important question, and it’s actually one of the major goals of the Human Microbiome Project that started in 2008. The method, which was very reasonable at the time, was just to survey in depth the microbiome of over 200 healthy individuals and to try to distill out common features. What became apparent over the course of studying this healthy American population and then other studies that started looking at traditional populations is that the microbiota that’s in a healthy American may not necessarily be a healthy microbiota. It may actually be a problematic microbiota that’s predisposing us to many of these diseases that will take decades to develop but which are partially a product of our microbiota.
So as the field has progressed and more and more of these populations that don’t live in industrialized areas, that live either hunter-gatherer lifestyles or rural agrarian lifestyles, what has become apparent is these traditional populations have much more microbial diversity, so many more types of bacteria in their gut microbiota, and then many of the types that they have are completely missing in the American population. It really suggests that we’ve somehow gone through a bottleneck through some aspect of our Western life or multiple aspects of our modern life, and it really has left us with this major question of, well, is it that inferred ancestral microbiota that would actually be healthier? Or maybe that would be more problematic now because of epigenetic changes and other environmental and dietary changes that just aren’t compatible with this community. So your question is a really profound one, and I don’t think we have a great answer to it yet.
I would say that the one thing that appears to be holding up and getting stronger—there’s more and more evidence lending to it—is that Americans have a low-diversity microbiota, but even if you look across the American population or European population, you see there’s a spectrum of microbiota diversity, and the people with the lower diversity have worse metabolic health and higher markers of inflammation. If you put them on a dietary intervention that increases their microbiota diversity, a lot of those markers get better. This still isn’t causal evidence, but it lends to this idea that we don’t want infinite diversity in our gut microbiota, there’s probably an optimal amount of diversity, but most of us in the industrialized world are probably operating below what an optimal amount of diversity is for the gut microbiota.
The Connection between Low Microbial Diversity and Disease
Chris Kresser: Mm-hmm. When you look at the research connecting changes to the microbiota and disease, is reduced diversity a major factor that you see across the board in studies looking at different disease states?
Justin Sonnenburg, PhD: By and large, that’s the case for the gut microbiota. I would say there have been a lot of studies that have taken a healthy cohort and a disease X, Y, or Z cohort and just looked at the species that are present in the gut microbiota, and typically if there’s a change in diversity associated with disease, it’s usually downward. In a lot of obesity studies that have been done, there’s much reduced diversity. A lot of times when there’s an inflammatory condition, there’s reduced diversity, but there are exceptions to this. If we shift over and think about the microbiota that resides in the vagina, bacterial vaginosis, a disease in another microbial ecosystem on the human body, that is typically associated with too much diversity. That’s typically a low-diversity ecosystem. So it really depends on the specifics, but I would say, by and large, for the gut, what we’ve seen is that reduced diversity typically partitions with a disease state.
Chris Kresser: What are some of the main causes of reduced diversity? I would imagine lack of fermentable fiber is the main one, but you mentioned a few others in your presentation.
Justin Sonnenburg, PhD: Yeah, there are the things that we can observe in experiment. If you give antibiotics to a person, you see that their microbiota diversity is greatly reduced and then gradually rebuilds over the following weeks and months as the community recovers.
There are other factors in the modernized world that are likely contributing to reduced diversity across the population. Cesarean sections are actually known to greatly influence the microbial community that first colonizes the infant gut, to the point where it looks more like a skin community from a C-section baby than a vaginal or stool microbiota from a baby that’s born through the birth canal. We don’t know the ultimate effect on adult diversity, but this is something that could affect the succession and building of a new microbiota as a baby is growing and developing.
Other things: We know that human milk has important molecules in it that help fuel the microbiota, these molecules called human milk oligosaccharides put there, it appears, for the express of feeding and assembling microbial community, attracting species like Bifidobacterium and Bacteroides species. This might be a factor, the fact that a lot of formula is used that doesn’t possess these compounds.
Then just overall sanitation. I think we just don’t share a lot of microbes. Again, all of these things have had great benefit to other aspects of our society, and so it’s a matter of figuring out the right balance, making sure that, for instance, C-sections are only used when they’re needed, and then perhaps if they are needed, there can be some medical practice that can compensate. There was recently a paper published, actually taking a swab of vaginal secretion from the mother and applying it to the skin of the newly born baby, the baby that was born by C-section, to influence skin community.
Chris Kresser: Yes.
Justin Sonnenburg, PhD: We just have to think in terms of ways that we can have the best of both worlds with this knowledge in hand.
Chris Kresser: Mm-hmm. I just saw another paper published, suggesting that Lactobacillus reuteri may be effective in helping to repopulate the gut after a C-section, although, to me, the vaginal swab makes a lot more sense in terms of getting a broader spectrum of microorganisms there that are particular to the mother.
Justin Sonnenburg, PhD: Right. I think this single-species idea is there’s obviously data out there to show that single species can have profound effects on ecosystems, and certainly that’s most apparent in the case of something like salmonella or shigella or Clostridium difficile pathogens, where a single species can go in and completely remodel the entire community and host situation. Certainly you can think about analogous situations for beneficial health, but I think you’re right, that ultimately what we’re look at is a complex consortium, and so it’s very likely that it’ll be mixtures of microbes that are the solution to a lot of these problems.
Can We Manipulate Our Microbiota?
Chris Kresser: Speaking of solutions, to what extent can we manipulate the microbiota? What does the data show on that now? How much control do we have over our microbiota, and what are the most important factors that are driving that?
Justin Sonnenburg, PhD: It’s a great question. There’s, again, an emerging picture that the microbes that we’re colonized with early in life can be with us for a long time, that they get privileged access to sites in our intestine that may allow them to exclude other species that are to the party second and third. So probably early life colonization events are incredibly important in dictating long-term trajectories and makeup of this community, although we know also that the microbiota can be changed really profoundly in a matter of a day or two with a big change in diet or with a course of antibiotics, if we kind of take the flipside of that. There are ways to greatly impact this ecosystem on very short timescales, and it suggests that as we gain more knowledge and better understanding of the ground rules of this ecosystem, that we may be able to nudge it one direction or another.
I think the prospect of, instead of thinking about drugging the microbiome, thinking about reprogramming it, thinking about how we may actually use entire consortia of microbes to remodel how this community is structured and the functions that it carries out. I think the fact that a major part of our biology is connected to this microbial community and yet the microbial community is malleable is just really profound. I think it’s changing the paradigm of biomedicine, of thinking about how we will exact change on human biology. It used to be that there was great emphasis on the possibility of gene therapy, that we could go in and manipulate our genome, and certainly the CRISPR-Cas9 Revolution has reawakened that sort of conversation, but I think that this idea that we have this major microbial component that we can change and shape over time is really profound, and it’s just a matter of figuring out the right ways to kind of nudge it into more healthy directions.
Chris Kresser: I just want to point out for listeners, when we talk about changes over time, some of these changes can happen pretty quickly. Right, Justin?
Justin Sonnenburg, PhD: Absolutely. There’s a beautiful study that showed that after just 24 hours, if you switch somebody from a meat-based diet to a plant-based diet, or vice versa, you get this really profound change in microbial community composition. Certainly what you’re eating is going to greatly change what this community is doing, and then there are other studies that have shown that long-term dietary trends are really important, that over the course of years, if you eat a certain way, you can kind of shape the microbial community to be built around that sort of diet. I think that the fecal microbiota transplants to cure Clostridium difficile are another situation where on a very short timescale with, in this case, therapeutic intervention of live microbes derived from a healthy person’s microbiota, you can just completely remodel a diseased microbiota, reboot it, and make it healthy again.
Chris Kresser: Right. After the FMT [fecal microbiota transplant], the recipient’s microbiota basically assumes a similar profile to the donor’s. Isn’t that right?
Justin Sonnenburg, PhD: Yeah, that’s exactly right. Over time again, that microbiota is shaped by some of the residents that were there that have hung on, it’s shaped by the dietary trends of the recipient, but ultimately it’s been well established that these microbes that make their way into the community during the transplant set up shop and basically set up a new microbial ecosystem.
What Inspired You to Write Your Book?
Chris Kresser: Mm-hmm. Justin, you’ve written a book about this topic, The Good Gut: Taking Control of Your Weight, Your Mood, and Your Long-Term Health. I’ve read it and I really enjoyed it. That was one of the reasons I was looking forward to meeting you at the UCSF event. I think you did a fantastic job explaining some potentially pretty complex topics in a way that most people can understand and also just imparting the importance of tending to your microbiota in order to protect your long-term health and prevent chronic disease. Tell us a little bit more about what led you to write this book and what your goal is with it.
Justin Sonnenburg, PhD: Yeah, sure. In my background as a basic scientist, I studied very specific molecules that are not of general interest to the general public for much of my PhD and postdoc, and as I became more involved in studying mechanisms underlying gut microbiota structure and function, I started to notice that I was changing my lifestyle and diet. My wife, Erica Sonnenburg, we’ve been working together for many years and run this lab together at Stanford. We have two daughters, and we noticed that we were raising our daughters differently over time as we learned more about this field and did more research. That involved diet. That involved lifestyle. We were eating a lot more fiber. We got a dog. We started gardening. We really paid less attention to washing our hands, just to make sure that we were introducing environmental microbes into our life, as long as we hadn’t been at a place where we thought there was a potential for acquiring some scary disease.
Chris Kresser: Right.
Justin Sonnenburg, PhD: We eat a lot of fermented foods now. As we were doing this, we noticed that a lot of our friends, scientists and nonscientists alike, were not doing a lot of the same things we were doing, and then we’d go to a microbiota conference where it was all microbiota researchers, and many of these researchers would be doing the same exact things that we’d be doing. We thought, well, this is really problematic, that we have access to information that has really convinced us to change how we live our lives, but that the information really isn’t available, or at least isn’t being well conveyed to the general public out there.
And so we wanted to capture that in a book, to just kind of write about the field broadly to inform people. It’s going to be incredibly important in medicine and health going forward, so there’s that reason, and then also just to convey our story, how this science has impacted us and our lifestyle and diet choices so that people can assess the data and then make decisions for themselves. It was actually through a connection with Andy Weil. I spoke at his conference a few years ago. He heard the story that I was just talking about in front of this group of physicians and healthcare practitioners, and he said, You have to write a book, and I’ll help you make that happen, and so that was kind of what was the catalyst for us doing this.
Chris Kresser: Great. Yeah, well, thank you again so much, Justin, for taking the time. I know my listeners are really going to appreciate this.
If you’re looking for a really in-depth, but accessible explanation of the microbiota and its importance in health, I can’t recommend Justin’s book highly enough. It’s sitting here on my shelf. It’s a reference that I turn to occasionally. Justin is a fantastic speaker and has a way of communicating these things that’s just really easy to understand, so check it out.
Justin, thanks again for your time. I really appreciate it.
Justin Sonnenburg, PhD: OK. Thanks for the great discussion, Chris. I enjoyed it.
Chris Kresser: Take care.
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