Gut Microbiome Plasticity | Peter Turnbaugh | 214

Short Summary: How diet shapes the gut microbiome and impacts health, with microbiologist Dr. Peter Turnbaugh breaking down the complex science. About the guest: Peter Turnbaugh, PhD is a professor of microbiology and immunology at the University of California, San Francisco, where he leads a lab studying the gut microbiome’s role in nutrition and drug response. Note: Podcast episodes are fully available to paid subscribers on the M&M Substack and everyone on YouTube. Partial versions are available elsewhere. Full transcript and other information on Substack. Episode Summary: Nick Jikomes talks to Peter Turnbaugh about the gut microbiome’s response to dietary changes, focusing on high-fat diets, ketogenic diets, and their effects on health. They discuss the pitfalls of oversimplified diet labels in research, Turnbaugh’s studies comparing plant-based and animal-based diets in humans, and how these shifts rapidly alter gut microbes and short-chain fatty acid profiles. The conversation also covers the microbiome’s role in drug metabolism, its links to inflammation and autoimmunity (like multiple sclerosis), and the potential of ketogenic diets to modulate these processes via ketone bodies like BHB. Key Takeaways: * The term “high-fat diet” in research is often misleading, as it can include high carbs and vary widely, complicating study comparisons. * In a 2014 study, switching humans to a plant-based (high-fiber) or animal-based (ketogenic, no-fiber) diet changed their gut microbiome within one day, showing its remarkable adaptability. * Ketogenic diets reduce Bifidobacterium in the gut, which may lower inflammation-linked immune cells (Th17), potentially aiding conditions like multiple sclerosis. * Short-chain fatty acids (e.g., butyrate) don’t just come from fiber; they persist even on zero-fiber ketogenic diets, hinting at alternative microbial pathways. * Gut microbes can activate or deactivate drugs, like antibiotics or digoxin, suggesting microbiomes may explain why drugs work differently across individuals. * Ketone bodies like BHB alone can mimic some ketogenic diet effects on the microbiome and immunity, simplifying research and hinting at therapeutic potential. Related episode: * M&M #203: Metagenomics, Microbiome Transmission, Gut Microbiome in Health & Disease | Nicola Segata *Not medical advice. * Full audio version: [Apple] [Spotify] [Elsewhere] * Full video version: [YouTube] [Rumble] * Support M&M if you find value in this content. * Episode transcript below. Episode Chapters: 00:00:00 Intro00:05:34 High-Fat Diet Issues00:11:00 Macronutrient Mapping00:17:29 Metabolic Adaptability00:25:59 2014 Study Design00:34:01 Microbiome Flexibility00:41:03 Fatty Acid Profiles00:48:41 Bile and Gut Changes00:55:09 Inflammation Links01:00:11 Keto Diet Exploration01:07:08 BHB Impact01:14:21 Microbiome Products01:19:35 Drug Response Research Full AI-generated transcript below. Beware of typos & mistranslations! Peter Turnbaugh 1:30 Sure. So I'm a professor in the department of Microbiology and Immunology at the University of California in San Francisco, and our lab is kind of broadly interested in how the gut microbiome, the trillions of microbes that are found within our GI tract, influence both nutrition and pharmacology. Nick Jikomes 1:51 Yeah. And so you study lots of interesting stuff. There's many different directions we could take this conversation. I've covered the microbiome a lot on this podcast. I've covered diet stuff a lot on this podcast. I want to start off pretty high level and talk about, get you talking about something that doesn't necessarily have to do with your work specifically, but it's, it's sort of broader questions related to diet and nutrition and how it's studied in the literature, and it obviously ties into the work you do. But I want to talk about some of the different types of diets that are out there that are commonly studied, and some confusion and shortcomings maybe even the literature has in terms of how those things are studied and how they're talked about. So the points I want to start is, I'm going to keep it vague intentionally, one of the most common diets that you'll read, if you dig into the scientific literature that has to do with the diet, is the so called high fat diet. And maybe some of the listeners, listeners will know from from listening to me before, but this is one of my biggest frustrations in the literature, this term high fat diet, what can you tell us about the high fat diet, and what that term maybe doesn't tell us, or problems that come from labeling and using diets with that level of specificity? Peter Turnbaugh 3:09 Yeah, that's a great question, and kind of near and dear to my heart. I don't know if you saw but we, we had a paper a few years ago where we did a meta analysis, where we were interested in, kind of comparing the microbiome profiles, mostly in mice, but also a little bit in humans. You know, across the hundreds of studies where people have fed mice some kind of form of a high fat diet compared to a control diet. And so, you know, something, we thought about a lot in that study. But you know, to your question, the the, you know, we, I guess going back to my work in grad school, we're kind of careful to use the term high fat, high sugar diet, because we thought, you know, when you especially when you think about the microbiome, it's important to keep in mind the kind of other macronutrient components and so like typically, when people model obesity and mice, they give them a diet that's not only high in fat, but also really enriched for sucrose and maltodextrin, you know, relatively simple carbohydrates that are readily digested by The host, but important, kind of stripping out a lot of the fiber or complex carbohydrate, Nick Jikomes 4:25 but, but importantly, when they give them these diets that are high in fat and high in these other carbohydrates, they simply usually call it high fat diet, right, right? Peter Turnbaugh 4:33 Exactly. Yeah, yeah. Typically like HFD, or like high fat diet is the acronym, which is misleading, you know, for the point you make, which is that it's actually different in terms of the types of carbohydrates. But even kind of more profoundly, you know, something that I think a lot of people don't realize is that, you know, normally, when we study lab mice, they're effectively eating whole foods. You know, given that it's. Largely soy and corn and other kind of commodity crops that are used to kind of, kind of smash together into these pellets, as opposed to your typical high fat diet, which is actually made from purified ingredients. So it's more like a processed food that you might buy in the grocery store. And so, you know, we think in terms of how the microbiome responds to these diet shows it's really important whether or not they're kind of seeing the nutrient in the context of a real food, as opposed to just, you know, a purified sugar. Nick Jikomes 5:34 Yeah. So, so when we read high fat diet in the literature, more often than not, it's not merely a high fat diet, it's high fat plus high carbohydrate. And if you compare, there's hundreds, if not 1000s, probably 1000s, of studies that use the so called high fat diet, or that, at least they use that nomenclature. But they can vary tremendously, not just in whether or not they also have high carbohydrate or high sugar content, but also the specific types of fats they use and all sorts of different things. And so it's, it's, it's a bit confusing, because, you know, if you were to just look at the literature and say, let's just look at all the studies that use a quote, high fat diet, and see what they say, it's actually not, it's just not appropriate to to sort of like, look at the one vector of where all those studies point. Because it's really many, many different diets that are simply, we're using the same words to describe, Peter Turnbaugh 6:23 yeah, totally. And, you know, that gets really kind of complex, especially if, like, every t… This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit mindandmatter.substack.com/subscribe