The future of gut health
Microbiologist Justin Sonnenburg wants you to know that you – and all humans, really – are not alone.
Inside each of us live uncountable bacteria without whom we could not survive. Nowhere is this symbiosis more vital, Sonnenburg says, than in the digestive tract – the gut – where trillions of bacterial collaborators help digest the foods that nourish us. Sonnenburg studies what makes this complex relationship work and how modern life is altering this important chemistry. He says the gut microbiome should be thought of as another organ. When it drifts out of balance, the effects ripple through our metabolism, our immune systems, and our nervous systems. Sonnenburg goes on to explain how dietary choices – like eating more fermented foods and fiber – can rebuild the microbiome, and why the field’s next frontier could help alleviate chronic disease. “It really is a full-body impact that our microbes are having,” Sonnenburg tells host Russ Altman on this episode of Stanford Engineering’s The Future of Everything podcast.
Transcript
[00:00:00] Russ Altman: This is Stanford Engineering's The Future of Everything, and I'm your host, Russ Altman. Since we started this show eight years ago, it's become an archive of amazing and impactful work by my Stanford colleagues. Research is not something that just happens in the lab, and as you'll hear on this show, the research at Stanford can impact areas like health, technology, law, and business, and many other topics that can affect everyday life.
[00:00:23] We hope you'll tune in to learn more about how research has the potential to help your life and to help the lives of people you care about in your family and your community.
[00:00:31] Justin Sonnenburg: I think the past 10 years of doing these dietary intervention studies has really shown us that on the one hand, diet can do a lot. That's one of the powerful messages of the gut microbiome field, is that this isn't restricted to just therapeutics and us do, having to do a lot of science first. Like, we kind of know what people should be eating and, I think people can really, you know, take the reins of their own health in, in fostering a healthy gut microbiome.
[00:00:59] Russ Altman: Stanford Engineering's The Future of Everything, and I'm your host, Russ Altman. If you like what you hear today, please follow the show. Your future self will thank you.
[00:01:07] Today, Justin Sonnenburg will tell us that bacteria in your gut are critical for your well-being. Not only that, but we can modulate our health by what we eat and change the bacteria that are living in our gut. That means that in the future, we may be even able to manipulate what we eat in order to help us respond and do better with specific diseases. It's the future of fiber and fermentation.
[00:01:32] Today, we're continuing our feature called The Future in a Minute. At the end of my conversation, I will ask Justin some pointed questions, and he'll give me some pointed answers. Before we get started, a reminder to follow the show and make sure that you get alerted to every episode, so you never miss The Future of anything.
[00:01:50] So many of us know that there are bacteria that live in our gut. A lot of times we think that these are dangerous, that we have to worry about bacteria because they can cause infections, which they can, and that's what antibiotics are for, for killing those bad bacteria. But what is sometimes lost is the fact that there are a huge number and diversity of normal bacteria in our gut that are not just okay, they're critical for our health. They help us digest food. They release molecules that interact with our immune system, our nervous system, and our metabolism. And so, they're absolutely critical for health.
[00:02:22] And the bad news is that with industrialization, there's been a change in our microbiome, in the bacteria that live in our gut, and this can adversely affect our health and has been connected with increasing rates of inflammatory and autoimmune diseases.
[00:02:36] Well, Justin Sonnenburg is a professor of microbiology and immunology at Stanford University, and he's an expert on the health consequences of manipulating the human microbiome in the gut. He'll tell us that we have a better understanding now of how to eat more healthy and have the right bacteria so that we can maximize our health generally, and he'll also tell us that there may be specific diseases that we can improve the treatments by modifying diet or bacteria.
[00:03:08] Justin, how did you decide to focus your research on how the bacteria that live in the gut influence our health?
[00:03:15] Justin Sonnenburg: Yeah, great question. First of all, thank you for the invitation. It's great to be here. I got very interested. I did my PhD in glycobiology, and I got very interested in the, all the carbohydrate motifs that coat all of our cells and started realizing that these were an interface for interaction, particularly with pathogens. That's kind of where it's best studied. Cholera toxin, flu, all these pathogens and their toxins bind to these carbohydrate motifs.
[00:03:38] And, so I started looking into, to post-docs and, and what was I gonna spend my career doing? And it really, was a, a new spin on this to think about these carbohydrate motifs being important in recruiting and maintaining interactions with friendly microbes rather than harmful ones. And these are, of course, are the, the commensals and, you know, what we refer to as, oftentimes symbionts or mutualists that live in and on our body, and our need to both escape pathogens, so changing these motifs so that we don't get attacked by the bad guys but not changing them too much to where we lose interactions with the good guys.
[00:04:15] And those ideas really started to pique my interest and, and then I found Jeff Gordon's lab at Wash U that was studying all of these, topics, and that's where I went for my post-doc, and the rest is history.
[00:04:26] Russ Altman: And the rest is history. Okay. So, what does somebody need to know who doesn't think about the gut microbiome all the time about, like, the normal state of, of the, and I know that even the definition of normal is somewhat contested, but what, how should we think about the bacteria in our gut? And I think people may be surprised to learn, first of all, that they're there and that they are friendly but secondly, how much they are part of the ecosystem of health in the body.
[00:04:52] So, maybe can you give us an overview for people who say, "What are you talking about? I thought bacteria were the kinds of things we killed with antibiotics."
[00:04:58] Justin Sonnenburg: Completely, and I think that is kind of the challenge of this field is we've all been raised in a, in a universe where Bacteria are the bad guys. We're, you know, trying to get rid of them. We have antibiotics. Those are obviously miracle medicines in terms of saving lives and preventing disease.
[00:05:14] But there is this other side of the story where we have evolved over millions of years, long before our species even arose, with microbes in the equation, and microbes that actually aren't necessarily trying to cause disease, they're just, you know, microbes are just interested in making more of themselves. And many of them found a good living just living in and on our bodies without causing disease, getting transmitted from one person to another.
[00:05:38] Over the course of evolution, this has resulted in what we refer to as a mutualism, where we benefit from having these microbes, and the microbes benefit from having this wonderful ecosystem where they get nutrients and can prosper and divide and, and all the things they like to do. And so, now we are fully dependent upon these microbes. I mean, it is like an organ, this complement of microbes that we have in and on our bodies and, you know, they're everywhere. They're not in our organs or in our bloodstream. That's, they shouldn't be there in the parts that should be sterile. But on our body surfaces, in our nose, in the vagina, but most of them reside in the GI tract, and that's what we study in my lab, the, the gut microbiome and, and most of the microbes there reside in the far reaches of the gut, in the colon.
[00:06:23] Russ Altman: Great. So, now when you write about the microbiome, the, the three of the big ones, and this is not exclusive, but three of the big kind of systems in the body that you talk about are the immune system, the metabolite system, small molecules in the body from nutrition, and the nervous system. So could you just-
[00:06:38] Justin Sonnenburg: Right
[00:06:39] Russ Altman: Connect each of those quickly? I mean, it's a ridiculous request, but welcome to The Future of Everything. Could you quickly connect those to like, okay, I have bacteria, how does that affect my immune system, my metabolism, and my nervous system?
[00:06:50] Justin Sonnenburg: Yeah. And I, I think this really is the counterintuitive part for a lot of people because if you have a lot of bacteria in your gut, and I should...
[00:06:57] We study bacteria, but there's all sorts of microbes there. So, there are viruses attacking the bacteria. There's,
[00:07:03] Russ Altman: Right
[00:07:03] Justin Sonnenburg: ... eukaryotes there. There... it's just this really... there's, archaea, this completely different domain of, of life. And so, it really is this complex ecosystem. You can think about it almost like a rainforest and all the different layers and interactions that are occurring.
[00:07:17] But I think it's, it's intuitive for people to, to think about these microbes being important in digestion and gut health. But what's-
[00:07:24] Russ Altman: Right. Right
[00:07:24] Justin Sonnenburg: ... remarkable is, you know, these microbes are sending chemical signals into our bloodstream. They're making little, little chemicals. They're secreting molecules off their cell surfaces. Those interact with our cells. They get absorbed into our blood system, circulate throughout our, our bodies, and have access then to all of our tissues.
[00:07:46] And so, that means when you change your gut microbes, when you change the composition or function of this community, those changes ripple through metabolism, through your immune system, and through your central nervous system, which may be hard to believe, but these microbes are even impacting neurodegeneration, moods, behavior. So, it really is a full body impact that our
[00:08:06] Russ Altman: Yeah
[00:08:07] Justin Sonnenburg: ... our gut microbes are having.
[00:08:08] Russ Altman: So, that's great. And, and really the key thing you said there, and I think we're gonna talk about this more, is that they, they secrete molecules, and, that, and those molecules, once they enter, enter the bloodstream, can of course affect almost anything, in fact, anything in, in our physiology. And so, in a funny way, immune metabolism and nervous are just the three big ones that, that you're able to measure.
[00:08:27] Okay. So, thank you. That was, now we have set the stage, and I wanna get right to it because you've written about the, the industrialization, of the gut microbiome. And, that could mean a lot of things, but tell me what, what you mean when you talk about, that our microbiome, that the bacteria that live in our bacteria have been industrialized.
[00:08:45] Justin Sonnenburg: I think one of the incredible features of the gut microbiome is that it's malleable. You know, and, and so it's this component of our biology that probably on the ancient savanna we benefited from this plasticity. As foods fluctuated over the seasons, our microbiome could adjust, help us digest what was coming down the pipe during that specific moment. And in fact, we've studied the Hadza hunter-gatherers in Tanzania and shown that their microbiome fluctuates seasonally, which, you know, of course has been totally lost in industrialized societies.
[00:09:15] But I think this malleability is a feature, but it also is a bug. So, it means that in the extreme circumstance, the microbiome can deteriorate at a really rapid rate when it experiences new insults like antibiotics or a food supply that has been industrialized that no longer contains the nutrients that support the microbiome, and instead contains, you know, crazy chemicals and weird, you know, artificial things-
[00:09:42] Russ Altman: Yeah
[00:09:42] Justin Sonnenburg: to, to light up our taste buds, but maybe not, not feed our gut bacteria. And so, you know, the, the factors are many. I've just named two there, but you know, everything from C-sections to baby formula to, you know, there's just all sorts of things in our modern world. You know, sanitation of the water supply, I think wonderful for controlling infectious disease, but maybe it has a, a negative impact on us being able to share beneficial microbes with one another.
[00:10:06] So, there really are these plus/minuses. Again, antibiotics, beautiful medicines, but this negative impact with all this collateral damage, 'cause they're meant to be broad spectrum killers, where they just will wipe out broad sections of bacteria. Because I think when these medicines were developed, it wasn't really recognized the importance of the gut microbiome and that there would be this negative impact.
[00:10:25] So, taken together, this picture, surveying across a lot of different lifestyles, what we understand is that ancestrally for tens of thousands, probably hundreds of thousands and millions of years, we had a relatively constricted set of bacteria that we would pass from generation to generation. And just over a very-
[00:10:46] Russ Altman: It's like a legacy.
[00:10:47] Justin Sonnenburg: Exactly, yeah. It, it really is.
[00:10:50] Russ Altman: Son, I would like to give you this microbiota for your life going forward.
[00:10:54] Justin Sonnenburg: You know, and, and that's, that's the thing is we see... And we've modeled this in mice. You know, we can take mice and just over four generations of giving them a Western diet, we see their microbiome whittles down to, like, a third of the species that it started with.
[00:11:06] There's just this massive, you know, kind of compounding extinctions that occur in the gut microbiome, and you can't bring those microbes back just by feeding a good diet at the end of that experiment. You actually have to purposefully reintroduce the microbes that you've lost, and maybe we can come back to this in how we recover health in our gut microbiome.
[00:11:25] But basically, we are like those fourth-generation mice where it's very clear we've just not only whittled down the diversity of this gut microbiome and lost a lot of the community members that we evolved with for thousands of years, but we have replaced them with other microbes, and these microbes appear to be pro-inflammatory in some of the, the early tests that are, that are going on in the field right now.
[00:11:48] So, we've replaced this co-evolved microbiome, and that's not to say that all those microbes are beneficial and great, but they're certainly the microbes that our body has become accustomed to. We've replaced those with another set of microbes that appear to be propagating inflammation, and we actually think this may be at the basis of a lot of chronic inflammatory disease.
[00:12:08] Russ Altman: So, what you say is extremely attractive. It's even somewhat intuitive. And I'm sure that the number one question you get then is, "Well, I'm in an industrialized society and there's a lot of things I can't change, but I can change what I eat." And I know this is something that you've been looking at, and you went all the way back, even in your origin story, you were looking at the sugars that are attached to proteins and to cells.
[00:12:29] So, and as you know, a huge market has arisen for health foods that are going to help our microbiota. So, I hope it's not premature, because I do wanna get to the serious precision health applications that you're studying. Yeah. But I think now is a good time 'cause I think people are asking, "What should I be eating?" because you also made reference to our diet changing and the seasonal diets in Tanzania. So maybe let's, let me ask you about that. What are the kinds of things that we're not eating that at least you have seen probably historically we were eating much more?
[00:12:59] Justin Sonnenburg: Yeah, completely. So, one of the insights that I think the field had early on was that most of the gut microbes live at the, the far reaches of the digestive tract, which means that if you're eating a, a diet that's rich in, like, sugar and protein and fat, like a Western diet, most of that gets absorbed in the small intestine, up at the top of the, the,
[00:13:19] Russ Altman: Right after the stomach
[00:13:20] Justin Sonnenburg: Right after the stomach. And so, if you're eating a Western diet, you- there's no food left over for the gut microbes in the colon. And historically, we ate diets that were, you know, I think hunter-gatherers, quite often people have images of them killing game and eating a lot of meat.
[00:13:35] Actually, if you go to the Hadza, the studies that have been done, it looks like that they eat mostly plants because those staples are always available. That's kind of what they rely on, but they just have to flux a lot of this plant material to get the nutritional value and calories out of it. So, they're eating on the order of 100 to 150 grams of dietary fiber per day. This is complex carbo, you know, dietary fiber is a crude term, but complex carbohydrates that we can't digest most of them.
[00:14:02] Which means that they pass through the small intestine, and that is what the gut microbiome is adapted to, is digesting these complex carbohydrates that are present in plant foods. In the industrialized world, we eat on the order of 15 to 20 grams of dietary fiber, so almost a tenfold decrease in this nutrient that fuels our gut microbiome.
[00:14:21] Now, that dietary fiber in the gut microbiome actually does two important things. It, on the one hand, serves as the fuel that allows the bacteria to produce beneficial metabolites, so things like butyrate, that actually fuel colonocytes, enforce the barrier, regulate the immune system in positive ways, regulate metabolism in positive ways. That's gone missing.
[00:14:42] And the, flip side of that is that our gut bacteria have started to eat the mucus layer as a backup food source. These carbohydrates that I mentioned at the beginning.
[00:14:52] Russ Altman: We're literally devouring ourselves.
[00:14:54] Justin Sonnenburg: Exactly. And, and these, these studies are just. It's one of the themes that it has persisted. You know, it, the, this was first described actually during my postdoc work. It's what you got, what got me the job here at Stanford, was discovering that these microbes can switch over to eating mucus if you deprive them of dietary fiber, and it's one of the themes that has just been very solid in the field.
[00:15:15] And we not only see that they devour the mucus, but that inflammation goes up, and then, you know, this is happening at the same time that we're watching inflammatory bowel disease rates, early onset colorectal cancer. All of these rates go through the roof that we know are directly related to inflammation in the gut. So, I think there's a direct connection there that's inferred, but really the studies need to be done to, to hammer this home.
[00:15:38] Russ Altman: And a, a great thing that you've made clear is that there's two things we need. Like, yes, eating more fiber is good, but you have to make sure you have the bacteria that can help you process that. So, it's, there's two things you need perhaps. You need the fiber at whatever appropriate level, and you need those bacteria that you as you've said, because of industrialization, may be lost and hard to get back. Is that...
[00:15:59] Justin Sonnenburg: Actually, perfect. So that, that, that actually... I wanna, I wanna reinforce that point because about 10 years ago, we started the Center for Human Microbiome Studies at Stanford to do human studies focused on diet. We did this with a close collaborator, Christopher Gardner. We used the immune monitoring center here run by Holden Maker, Mark Davis, a beautiful, system that allows us to monitor the immune system in really high-dimensional ways so we can understand what's happening to somebody's inflammatory tone.
[00:16:23] Russ Altman: Yes
[00:16:24] Justin Sonnenburg: As they're on different diets longitudinally. And so, with Christopher Gardner, we have done dietary fiber interventions. And what we see is, and we, we've done about 10 or so dietary interventions over the past 10 years in human cohorts, different human cohorts. And what's been remarkable is that for dietary fiber, only about a third of the healthy adults that we enroll in these trials can respond positively to the dietary fiber. That is, they actually make butyrate, they actually decrease their inflammation, exactly the signal we'd wanna see.
[00:16:57] Two-thirds of them cannot. Those two-thirds of the population actually have the lowest diversity, most deteriorated gut microbiome, and a lot of fiber coming through in their stool. So really, the implication there is exactly what you're saying. You not only need to have fiber, but you need to have the right microbes.
[00:17:14] Now, just to interject one thing here, because I think it's an important side point, we have also studied a lot of other diets, and the big signal that we didn't really expect and wasn't really appreciated in the field before, fermented foods have an incredibly positive impact on the gut microbiome. So, this would-
[00:17:31] Russ Altman: Right. That was exactly where I was gonna go. Can you tell us what does it mean? I mean, when we think of fermentation, most of us think about people in Kentucky making bourbon. But so, tell, what, what's the definition of fermented for you?
[00:17:45] Justin Sonnenburg: Yeah. So fermented foods that we used in this study, and that's, that's a very good point. We get asked the alcohol question quite often, and we're, we'd be happy to do a bourbon study if somebody wants to fund it. I would, I would enroll but-
[00:17:57] Russ Altman: I have a friend named Johnny who might wanna fund it.
[00:17:59] Justin Sonnenburg: Okay, great. Great. you know, we, we, took this to mean for fermented foods, basically like yogurt, kimchi, sauerkraut, kombucha. So, these are foods that are transformed by microbes. You buy them in the refrigerated section in the market, or you make them at home. They contain not only the live microbes, but they also contain all the metabolites that the microbes have made while they've been fermenting.
[00:18:23] Russ Altman: Okay.
[00:18:23] Justin Sonnenburg: So, like lactic acid is a common one that people think about, but there's hundreds of different molecules in there that are produced by the, by the microbes. And then the other important point is they actually have reduced glycemic index because all the microbes have consumed all the simple carbohydrates. So, they're really wonderful foods. And we've now conducted a, a couple trials with these with just magnificent results in terms of the, the impact on the microbiome and on host biology.
[00:18:48] Russ Altman: Because they're bringing both the bacteria and the kind of nutrients that you would want to the party. It's not just half the story. It's the whole shebang, so to speak.
[00:18:57] Justin Sonnenburg: Exactly. But we still don't know all the mechanisms of this, and that's the really, there's just a lot of science to do here that's really interesting.
[00:19:04] But we know we're on the right track. What we see is when we give people fermented foods, their microbiome diversity increases, so the signal we'd wanna see to counter the deterioration that occurred during industrialization. And not only increased diversity, but we see recruitment of butyrate-producing bacteria, and you know, exactly the, the kind of strict anaerobic fermenters that we'd wanna see.
[00:19:25] We see a decrease in many inflammatory markers, so over two dozen different inflammatory markers go down, so you know exactly what we'd wanna see to counter the rise of chronic inflammatory diseases. And now we're actually performing this. So that was originally a study that we did in healthy adults. Now we're doing this study in pregnant women to see if we can cultivate a more diverse gut microbiome in them, that then they pass to their infants with the idea that we could reverse what I described before with that four-generation.
[00:19:55] Russ Altman: The legacy is back.
[00:19:56] Justin Sonnenburg: Exactly. Can, can we reverse this?
[00:19:58] Russ Altman: This is The Future of Everything. I'm Russ Altman, and I'm speaking with Justin Sonnenburg from Stanford University. We've been discussing the gut microbiome and its relationship to health. Immune system, nervous system, metabolism, everything you can think of could be affected by the bugs that are secreting small molecules into your bloodstream.
[00:20:17] We're gonna now move to therapeutic approaches. How can we use this to improve people's health, either in general or in the context of specific diseases? But before that, don't forget, at the end of the episode, we're gonna have the Future in a Minute, where I'll ask Justin five pointed questions, and he will give me five pointed answers.
[00:20:36] So Justin, you've worked up, us up into a frenzy. And we're excited about these, the dietary things, the fermentation, the bacteria working on us. But what's the opportunity for actually using this to improve health?
[00:20:49] Justin Sonnenburg: You know, I think the past 10 years of doing these dietary intervention studies has really shown us that on the one hand, diet can do a lot.
[00:20:55] So, I encourage everybody out there, you know, that's one of the powerful messages of the gut microbiome field, is that this isn't restricted to just therapeutics and us do, having to do a lot of science first. Like, we kind of know what people should be eating, and I think people can really take the reins of their own health in, in fostering a healthy gut microbiome. Now, it's a, it's a long road. It's a, it's a habitual thing. It doesn't all happen within a six-week dietary intervention.
[00:21:19] But so, so diet's powerful, but I do think that if you use diet alone, it can be a slow road because we have to acquire from around us all the right microbes if we have a, a deteriorated microbiome. And in our sanitized world, that can be a slow process. So, I think that the opportunity for the field right now is to bring back functions that have been lost in the industrialized microbiome. And, and you know, there's a lot of them out there, but one of the key ones that we've been focusing on is this ability of the microbiome to consume dietary fiber, break it down, and turn it into short-chain fatty acids like butyrate.
[00:21:55] So, if we could reinstall that function into everybody's gut microbiome, it's such a critical node of homeostasis in the gut that I think that that would have a really big role. We've just gotten a grant from the NIH to do this. We've been supported by philanthropy through Stanford Development, wonderful kind of team effort here from the community. And we are now building microbial consortia that we can give back to people and feed them fibers
[00:22:21] Russ Altman: You don't mean consortia of scientists. Sorry. You mean consortia of bacteria.
[00:22:25] Justin Sonnenburg: Consortia of bacteria, exactly. So, bringing back a healthy ecosystem, feeding it the right food, these complex carbohydrates, maybe some other molecules that we're finding are important to drive a very anaerobic environment to encourage fermentation in the gut, and basically pursuing a bugs plus diet approach to fixing the industrialized microbiome.
[00:22:46] I think this could have a massive impact on a range of diseases out there, both intercepting them at an early stage, but also preventing everything from food allergies to celiac to a lot of the more profound life-altering chronic inflammatory diseases.
[00:23:00] Russ Altman: I want to get to that, but a, a quick question. Somebody who's, who doesn't really want to change their diet, they like what they're eating.
[00:23:06] Justin Sonnenburg: Yeah.
[00:23:07] Russ Altman: And you were, we were talking about these small molecules that the bacteria are putting out. So is there a way to shortcut all this and just give me a, oh goodness, this sounds terrible. Can you Justin, can't you just give me a pill with all of those small molecules so I don't have to change my diet, but I can still have all these benefits?
[00:23:24] Justin Sonnenburg: Sure, and I know what you're saying. I'm, and I'm not philosophically opposed to this. I, I mean, I do love the idea of people eating beautiful, healthy diets. I know it's not necessarily scalable immediately. I know it's just based on people's-
[00:23:34] Russ Altman: It can be expensive, too, so there is a justice and equity aspect to this.
[00:23:37] Justin Sonnenburg: Exactly. Yeah, exactly. Exactly. And so, we are thinking about, like, how could you have a sachet? Of, you know, the kind of food components that you would need to fuel these bacteria so people wouldn't have to do massive changes to their diet, 'cause that can be, just from doing these dietary intervention studies, we're very lucky to partner with the Gardner Lab, very difficult to get people living in a free and affluent society to eat differently than how they've, eaten their whole
[00:24:02] Russ Altman: life.
[00:24:02] Right, right. And, and we're gonna get to disease, but I had one other quick question, which is we are a social animal, and you were talking about, like, we can get, like, bacteria from... People who live in the same home often have a very, if I understand correctly, often have a very similar microbiome.
[00:24:16] So, if I wanna get back my legacy of bacteria, should I go hang out with my granola-eating, fiber-eating friends who live up in the mountains? I mean, is that gonna get me, is that increase the chances that I'm gonna get the right kind of bacteria? So, so should I hang out with healthy people in order to become more healthy?
[00:24:34] Justin Sonnenburg: Yeah. I would say that the jury's still out on this, but I, I would say it's a, it's a sound theory. It’s a good hypothesis. There have been studies that have shown that, so for instance, early studies in the microbiome field showed that you could actually transmit obesity in both mouse models and from humans to mice just by transferring the gut microbiome.
[00:24:52] Russ Altman: Okay.
[00:24:53] Justin Sonnenburg: And we also know from beautiful work from other labs that you can actually block that process with healthy microbes from the healthy mice. So, so it is, it is what you're saying, but it, you know, I think it is a slow, you know, there are gut microbes everywhere. I love the, the phrase that the world is covered in a patina of shit, and we're constantly doing low-grade fecal transplants on ourselves, and whether the good microbes stick or not is probably largely dependent on what we're eating. So, I think combining exposure to healthy microbes,
[00:25:23] Russ Altman: Yes
[00:25:23] Justin Sonnenburg: ... and, and healthy diet is the recipe to get back on track.
[00:25:26] Russ Altman: And, and you've just painted for us a beautiful pageantry of imagery. Thank you so much.
[00:25:30] So okay, let's go to disease. You, you, I... Before I interrupted with my two questions, you were starting to get to, you were talking about serious diseases, celiac disease, I know you've written about cancer. So how in the world... So, there's one thing to kind of just make me generally healthy with good microbes, good, good diet, but is there a possibility that specific diseases will benefit from some manipulations of the, of the microbiome and the diet perhaps?
[00:25:54] Justin Sonnenburg: Yeah, great. Without a doubt, and the, the really interesting part there, I think, is that it may not be the same for everyone, and it may not be the same as the principles that I've been telling you for just fostering a healthy gut microbiome in some of these instances.
[00:26:08] So, a good example of this, there's just been a ton of beautiful work in the cancer immunotherapy world, and it's known that these immunotherapies are magical for some people, and they don't work for other people. This is, these are therapies that actually activate your immune system so that your immune system attacks the cancer. And it's known that microbiome profile actually corresponds to whether you respond to the therapy or not. And the studies have been expanded to animal models that show that you can actually add microbes as kind of therapeutic microbes to change that response rate.
[00:26:42] So, the future is clear. We're gonna be able to tune the immune system or tune metabolism to actually benefit people in different situations, whether it's immunotherapy or a different autoimmune disease. It may be people that just want to run a marathon faster or want to do better cognitively on a test or want to conceive a child. We may want to dial biology to different spots based on whatever somebody's going through at that moment and based on their human genome and their own microbiome. And so, this gets to the idea of using the microbiome in precision health.
[00:27:13] I think it's gonna be one of the major levers that we have because it's malleable, and it's connected to so much of our, you know, basically all of our biology in some way. And that means once we learn the rules and learn how to manipulate it, we're gonna have this great tool at our disposal for helping everyone. It's just very complex, so we, we have to do the work to get there.
[00:27:32] Russ Altman: You've made a couple of references to women's health during our conversation, and, and you mentioned pregnancy and vaginal health. Is that one of the target areas that looks like it could be fruitful?
[00:27:41] Justin Sonnenburg: Totally. And there are kind of two aspects of that. There's the reproductive health side, and then there's just women's health in general. And I would say that those are two areas where it's known that the microbiome plays a massive role and has been massively underfunded and understudied.
[00:27:55] So, I think there's huge opportunity there. It's an area that we really wanna cultivate at Stanford, and I think looking for people that are interested in, you know, I wanna give a plug here to our wonderful philanthropists. Some of the most exciting work that we've done and risky work that we've done is not fundable through the National Institutes of Health, which is another amazing funder, but a little bit more conservative in what they fund. And so, we've just had wonderful partners in the community here that have funded a lot of our most risky, risky research, and I would say that that's where the big discoveries come from.
[00:28:29] And we're looking for that in many different areas, but women's health is, is one of them for sure.
[00:28:33] Russ Altman: You, you've made reference to, a community of scientists, of course nationally and globally, but also locally that you work with. So, this sounds like it's very much an interdisciplinary field. And I guess to end, tell me a little bit about how you're setting it up for the future research programs. You've already made some references to the funding agencies, but when they give you the money, how do you set it up for success?
[00:28:53] Justin Sonnenburg: Yeah. Great, great question. So, we're in a massive effort right now to try to, you know, I, I would say Stanford is one of the leading universities in terms of microbiome research. We just have incredible people here at Stanford, and we're right now building something where we can turn these. They're not islands of excellence. There is a lot of collaboration that happens, but it, it happens kind of spontaneously. We wanna organize that a little bit and create a front door for all the people who are not microbiome experts but see important applications to their, their field.
[00:29:24] So, we're starting this next phase of our, our human studies center where we really hope to expand this into the clinics. We're developing microbiome function tests. We are, you know, KC Wong in, in bioengineering is doing amazing things with a small intestinal, you know, capsule that can
[00:29:41] Russ Altman: Yes
[00:29:41] Justin Sonnenburg: ... sample the microbiome, and we expect a whole group of therapies to come out of that.
[00:29:46] You know, Michael Fischbach, David Relman, who's been here for years, and then Sean Spencer in the clinic, a brand-new faculty member. We have the first director of microbiome therapeutics and diagnostics in the hospital now in GI, and so he's brand new. His goal is to build out an incredible clinical operation.
[00:30:04] Ami Bhatt, Dylan Dodd, there's just like an incredible community of, of microbiome researchers here, and I think we are at the cusp of doing something monumental, both in terms of changing the trajectory of human health locally, like we think about the United States. But I think globally, when you think about industrialization spreading and Western diseases spreading with this lifestyle, I think that we could have a, a massive impact on healthcare spending and certainly suffering and, and untimely deaths.
[00:30:36] Russ Altman: So that's just fantastic, and congratulations on this work. Before we finish up, I wanted to ask you if you're ready to do The Future in a Minute.
[00:30:44] Justin Sonnenburg: Yeah, absolutely.
[00:30:45] Russ Altman: Great. So, I'm gonna ask you five questions, and you'll give me five answers. Thank you so much, and here we go. What is one thing that gives you the most hope about the future?
[00:30:54] Justin Sonnenburg: You know, I think for a long time in the microbiome, we knew it was important, and we didn't know exactly what we should be doing, and there's been about 15 to 20 years of a massive field doing a lot of work.
[00:31:04] And I would say we now know a large portion of what we need to do, and we just need to do the work to get there. It's still complex, but I, I think we know where we're going, and there's, like, this is gonna be a massively important field over the next 10 years.
[00:31:19] Russ Altman: What's one thing you want people to walk away from this episode remembering?
[00:31:23] Justin Sonnenburg: Daily decisions that you make, diet, medical decisions, other aspects of your lifestyle, are impacting this complex community of microbes that are our lifelong partners and incredibly important for our health. So, just become educated and, and think about those decisions.
[00:31:42] Russ Altman: Aside from money, what is the one thing you need to succeed in your research?
[00:31:47] Justin Sonnenburg: People. So, you know, I, I think when it comes back to doing science and, particularly attacking, like, big, difficult problems, you really need great collaborators because it's, is probably gonna be interdisciplinary, and, you know, very difficult problems just require a lot of different disciplines and perspectives.
[00:32:05] And then great trainees. And, you know, this is something at Stanford that we're very, lucky to have. But I, I think that the people here have really been a, a big part of the equation and will always be super important in driving forward the research.
[00:32:19] Russ Altman: If all goes well, what does the future look like?
[00:32:22] Justin Sonnenburg: We're all used to seeing these disease trends in terms of disease prevalence for Western diseases go up over time, the projections of them continuing to go up. I think if we do this correctly, we could see those curves reverse, where actually diseases become less prevalent over time.
[00:32:40] Russ Altman: If you were starting over again and you needed to get your degree or certification in a different discipline, what would it be?
[00:32:46] Justin Sonnenburg: I would have to say climate science. I mean, I just think this is the biggest challenge facing humanity right now. That's a big area. I would say probably out of all that, maybe forestry. I grew up in the forest. I love trees. If I could have a job that would allow me to visit the forest more, that would be pretty awesome.
[00:33:04] Russ Altman: Thanks to Justin Sonnenburg. That was the future of fiber and fermentation. Thank you for listening to the show. Don't forget we have over 300 back episodes that you can listen to, and you can spend a lot of time thinking about the Future of Everything. If this episode gave you something useful, please share it with a friend, neighbor, colleague, or family member. That'll help grow our show, and we would love to have a bigger community.
[00:33:26] You can connect with me on many social media platforms such as LinkedIn, Bluesky, Threads, and Mastodon, where I'm @RBAltman or @RussBAltman. You can also follow the Stanford School of Engineering @StanfordSchoolOfEngineering or @StanfordENG.
