#070 Dr. Eran Elinav on Microbiome Insights into Personalized Response to Diet, Obesity, and Leaky Gut

Omega 3 Discussion

Welcome back to another episode of the Found My Fitness interview series. This episode features Dr.

"Welcome back to another episode of the Found My Fitness interview series. This episode features Dr. Iran Ilinov, a renowned expert on the gut microbiome and how it influences human health and disease. I'll tell you a little bit more about who Dr."

Gut Microbiome: Diversity

Welcome back to another episode of the Found My Fitness interview series. This episode features Dr.

"Welcome back to another episode of the Found My Fitness interview series. This episode features Dr. Iran Ilinov, a renowned expert on the gut microbiome and how it influences human health and disease. I'll tell you a little bit more about who Dr."

Omega 3 Discussion

I can only say we're on it. I know you've written about it in really well done review articles that you've published.

"I can only say we're on it. Stay tuned. Great. So we've been talking quite a bit about obesity throughout the podcast and how the gut microbiome is affecting obesity. And I want to kind of dive into that a little bit more."

Gut Microbiome: Diet

One could argue also that the lack of dietary composition or lack of a type of food could also play a role as well. Can you describe the differences between these?

"And so there's, again, a lot of, you'll see a lot of conflicting evidence and you're trying to figure out, well, what do I eat? What do I eat? What do I not eat? What role does the microbiome play in the production of TMAO, which is thought to be associated with heart disease? Yeah. It's a great question based on a great set of stories by Stan Hazen's group, which I think contributed a very important concept to our understanding of how the microbiome cooperates with the human body in generating together compounds which may impact human health. So in this particular case, we're talking about a connection between dietary compounds such as choline and carnitine, which are digested by the microbes into a compound called TMA, which then influxes into the host and is further converted by the host, by the liver of the host into TMAO. and this TMAO swims into the circulation, where in some instances, it could impact macrophages that form plaques that are responsible for atherosclerosis, and it's potentially devastating health effects, heart disease, brain disease, kidney disease, and more. So from a fundamental microbiome perspective, this is a fine example of a cooperation that exists between dietary cues that are perceived by the microbes and then further modulation by the host that leads to a health outcome. Now, you're absolutely right that if you look at a health perspective, and now I'm speaking as a physician, you know, you cannot explain atherosclerosis by just one factor. You cannot say that, you know, one type of microbial reaction or one type of food or even one genetic risk factor in a human individual would explain the entire spectrum of this huge and highly variable disease. But by definition, these common multi-factorial diseases are influenced by a combinatorial collection of risk factors. And I think what this fascinating study has provided was the proof of concept on how mechanistically one could explain the influences of particular types of diet and the microbes on the risk Thank you. of concept on how mechanistically one could explain the influences of particular types of diet and the microbes on the risk of developing a particular disease in some individuals with other risk factors that contribute to this disease. So I would never expect that every individual that would be exposed to the same levels of carnitine or would feature the same bugs that convert choline into TMA would develop heart disease. It's a combination by many different risk factors. Coincidentally, we've recently published another study focusing on a peculiar type of obesity that develops after cessation of cigarette smoking. And to make a long story short, we found a similar cooperation between the microbiome and the host in generating compounds that could drive this obesity phenomenon after smoking cessation. So it seems that the concept which we term the holobion concept in which you can regard a human as a combined set of microbes and human cells could contribute to many of the more complex health outcomes that are so concerning to many of us. Well, with that said, this has been a really interesting conversation, Aron Thank you so much. And we've talked a lot about precision medicine, personalized nutrition, and how people respond differently to foods. So it's a little hard to, you know, come up with a top lifestyle modifications or, you know, to improve gut health. But, you know, in your opinion, are there some low-hanging fruit? We are not there in terms of our precision medicine and personalized nutrition yet. We're beginning to understand a lot more about it thanks to research from your lab and others. But are there some low-hanging fruit, things that like, you know, maybe perhaps consuming foods that have some of these fermentable fibers or prebiotics, like you mentioned, or fermented foods that also have probiotics and things like that? It's a great question and a question that I'm being asked very often. I can tell you that what we've been discovering in our own studies, even without looking into the personalization aspect, is that some of the behaviors which your grandmothers would recommend to you are also beneficial in terms of what they do to the microbiome. So, for example, maintaining healthy sleep patterns and avoiding as much as possible erotic sleep weight behavior has very profound effects on our measurement of the microbiome and how it impacts our regulation of weight and glucose or sugar metabolism or the avoidance of type 2 diabetes, for example. In terms of fibers, you know, in general, I think that the data is quite solid in promoting fibers as a good, you know, family of foods to consume. However, I must say that we and others are engaged in very exciting studies, which suggest that even with fibers, not all fibers are created equally. In other words, you know, even fibers are composed of many different chemical formulations that differ from each other in the way that they are consumed by the microbes and impact the human body. So even with fibers and with the generally beneficial effects that have been observed with them, it seems that some fibers are better than others and we're trying to contribute towards new knowledge that would refine these recommendations in different individuals and with different fibers. You know, smoking seems to be a universally bad behavior for many reasons, but when we measure what it does to the microbiome, we were intrigued to find that many cigarette related chemicals not only reach the systemic circulation, but they actually penetrate the gut and they impact the microbiome towards a disturbed composition and function. And this has its own independent effects on, for example, the risk of developing obesity after you attempt to stop smoking. So all of these behaviors, which in many cases we know are probably not good for us, are also not good for us in terms of their effects on the microbiome. Beyond this, I think that we need data, we need knowledge, we need to increasingly learn to harness diet to the individual in order to really optimize the power of the microbiome in impacting human health. And what about the timing of our food intake? Would you say that's a pretty top? I can tell you that in our personalized nutrition, machine learning algorithms, which are used to predict a person's dietary responses in a very accurate manner, the timing of our diet, and even the timing of our meal last night are part of the features that are used by this unbiased algorithm in order to form its very accurate predictions. In other words, it seems that the timing of our diet is important for many different aspects coming from many different studies by us and by others. What we do with it, in addition to trying to time our diet in a kind of normal and routine manner, is still under review or under research. So this algorithm that you were just referring to, so this is a company that was, was it started by you or? Yes. So basically the personalized nutrition project was an ambitious project, which was headed by me and my colleague Aaron Sigal, who is a mathematician from the Weizmann Institute of Science. And we started with this project back in 2012. and this was a study that was first published in 2015 and formed the cornerstone of what we call personalized nutrition today. And in this study, we analyzed the data from a thousand individuals in Israel that kindly gave us a week of their life. And we measured and collected an unprecedented amount of microbiome and host-related data, including a smartphone app that was used in this study and continuous glucose measurements that generated very accurate measurements of sugar responses to food in a week of follow-up. And then a very sophisticated machine learning and AI technologies were used to generate predictive algorithms for each individual that are able to accurately predict a person's sugar responses to any given food. And this eureka moment was the basis for personalized nutrition because it allowed us for the first time to formulate diets that are different between individuals, but would hopefully lead to normalization of blood sugar levels. And this was tested by us in different contexts, including recently in a long-term randomized human trial, which compared this data-driven personalized approach to the gold standard American Diabetes Association recommended diet. And we've quite convincingly showed that this personalized science-driven approach was outperforming the current one-size-fits-all diet in a large group of pre-diabetic individuals, which are individuals already predisposed to develop disturbances leading to type 2 diabetes. set of discoveries has been repeated by other groups across the world and is gaining track and basically tells us that data coming from the host, from the human host, and data coming from the microbiome could be combined using advanced technologies in order to predict and maybe to impact dietary interventions at different clinical contexts. So this company, I know it's called Day2, and does a person have to wear a continuous glucose monitor or like, you know, there's a bunch of biomarkers that need to be done to try this out? Yeah, so that's a great question. And just to make clear to our audience, all the research that I've stated was academically done in an academic setting without any company involved. But following the publication, the Weizmann Institute of Science have licensed the technology to a spin-off company called Day2, which further developed it for massive use in upscaling by many more individuals. What the advantage is of day two as a company is that now that they've performed over 100,000 tests on 100,000 people and more, the quality of data that was collected is so great and the resolution is so great that the people that are now engaged no longer need to go through all the procedures that characterize the early studies and they don't even need to wear our continuous growth as monitor anymore. In other words, a person can now provide a stool sample that can be shipped through the mail, plus some commonly available clinical parameters that they can provide through the internet, and then an accurate prediction of that person's glycemic responses or sugar responses to foods and recommendations that are peculiar and specific for that person could be provided because of the background database that was already created. Now, I'm not part of the company. I'm one of the two scientific founders of the company, but the company is now running on its own, mainly in the U.S. and is available in the in the US. And the findings that we discovered have been reproduced by others in other human studies in the UK and in the US. There are other commercial entities that are developing the same approaches. I can tell you that in the book we published called The Personalized Diet, in addition to our story, we also describe a kind of a do-it-yourself, a non-commercial way to exploit these discoveries. For example, by buying a glucose monitor that you can purchase in your local pharmacy and by skin-pricking yourself and measuring your blood sugar responses after some of the foods that you usually consume at your daily lives, you can now start to tweak your diet and to change ingredients in your diet in reducing your sugar responses after meals. So you can do it yourself in, of course, much less sophisticated manner, but you can use the same principles that we've discovered in changing elements in your diet and making your sugar responses lower than before. So it sounds like you're a proponent of people wearing a continuous glucose monitor. I've worn one for the past, oh, almost three years. And I have learned an immense amount of very interesting information from wearing one. Probably one of the most surprising ones early on, I started wearing it when I was a new mother, and was the effect of lack of sleep on how the way my body responded to the same foods that I've always eaten in terms of my postprandial glucose response. And it was completely out of control when I was...when my sleep was disrupted. You know, there are people that...there are scientists and researchers out there and physicians that do not like the continuous monitor, you know, glucose wearing approach because they claim that it, you know, urges people to not eat a healthy fruit or something like that because it may elevate their blood glucose level. What do you think? Well, I'm not sure I would like to propose that every person wears a continuous glucose monitor, but I respectfully disagree with those who say that, you know, measuring yourself or using science and technology in order to improve, you know, what you do in your daily lives would, you know, be wrong. I think that, you know, disregarding all the advances that science is proposing to us and not utilizing these advances for our benefit would probably make us miss a lot of the good that science has to offer. So by, you know, by wearing a continuous glucose monitor, you probably experienced many surprises and maybe, you know, we've done thousands of people and I can tell you that almost in any person that we've measured, we found counterintuitive surprises. Some people spike their blood sugar to the roof when they eat tomatoes. Now you combine tomatoes with some white bread and the response goes down. So, you know, by not doing the experiment or by not measuring themselves, they would devoid themselves from the benefits of knowing what is good and what is less good for themselves. So I'm all for measurement. I'm all for knowing and for doing this rationally and carefully, but doing it. I'm in 100% agreement with you. So your book is the personalized diet. You co-wrote it with your collaborator, Dr. Aaron Sengal. Seagal. Oh, Seagal? Yes. Okay. And Day 2, which is now licensed by the Weitzman Institute for Science, is the app you were talking about. But again, thank you for talking about the alternative approach with perhaps even people getting a continuous glucose monitor. If people want to follow you, you're on Twitter. Your Twitter handle is elinav underscore lab. So that would be E-L-I-N-A-V underscore lab, L-A-B. And you also have two lab websites. If you Google your name, Ilan, E-L-A-N. Yes, Ilanov, I-L, sorry, E-L-I-N-A-V. You'll find all the lab research that you're doing. Phenomenal, I mean, amazing impact that your research has had on our understanding of the interaction between the microbiome and in our gut and human health. And I'm so happy that we were able to connect and have a conversation today. I've been a big fan of your research for a long time now. So thank you so much for coming on the podcast and taking time to have this very interesting discussion with me."

Personalized Nutrition Discussion

Well, with that said, this has been a really interesting conversation, Aron Thank you so much. But, you know, in your opinion, are there some low-hanging fruit?

"And so there's, again, a lot of, you'll see a lot of conflicting evidence and you're trying to figure out, well, what do I eat? What do I eat? What do I not eat? What role does the microbiome play in the production of TMAO, which is thought to be associated with heart disease? Yeah. It's a great question based on a great set of stories by Stan Hazen's group, which I think contributed a very important concept to our understanding of how the microbiome cooperates with the human body in generating together compounds which may impact human health. So in this particular case, we're talking about a connection between dietary compounds such as choline and carnitine, which are digested by the microbes into a compound called TMA, which then influxes into the host and is further converted by the host, by the liver of the host into TMAO. and this TMAO swims into the circulation, where in some instances, it could impact macrophages that form plaques that are responsible for atherosclerosis, and it's potentially devastating health effects, heart disease, brain disease, kidney disease, and more. So from a fundamental microbiome perspective, this is a fine example of a cooperation that exists between dietary cues that are perceived by the microbes and then further modulation by the host that leads to a health outcome. Now, you're absolutely right that if you look at a health perspective, and now I'm speaking as a physician, you know, you cannot explain atherosclerosis by just one factor. You cannot say that, you know, one type of microbial reaction or one type of food or even one genetic risk factor in a human individual would explain the entire spectrum of this huge and highly variable disease. But by definition, these common multi-factorial diseases are influenced by a combinatorial collection of risk factors. And I think what this fascinating study has provided was the proof of concept on how mechanistically one could explain the influences of particular types of diet and the microbes on the risk Thank you. of concept on how mechanistically one could explain the influences of particular types of diet and the microbes on the risk of developing a particular disease in some individuals with other risk factors that contribute to this disease. So I would never expect that every individual that would be exposed to the same levels of carnitine or would feature the same bugs that convert choline into TMA would develop heart disease. It's a combination by many different risk factors. Coincidentally, we've recently published another study focusing on a peculiar type of obesity that develops after cessation of cigarette smoking. And to make a long story short, we found a similar cooperation between the microbiome and the host in generating compounds that could drive this obesity phenomenon after smoking cessation. So it seems that the concept which we term the holobion concept in which you can regard a human as a combined set of microbes and human cells could contribute to many of the more complex health outcomes that are so concerning to many of us. Well, with that said, this has been a really interesting conversation, Aron Thank you so much. And we've talked a lot about precision medicine, personalized nutrition, and how people respond differently to foods. So it's a little hard to, you know, come up with a top lifestyle modifications or, you know, to improve gut health. But, you know, in your opinion, are there some low-hanging fruit? We are not there in terms of our precision medicine and personalized nutrition yet. We're beginning to understand a lot more about it thanks to research from your lab and others. But are there some low-hanging fruit, things that like, you know, maybe perhaps consuming foods that have some of these fermentable fibers or prebiotics, like you mentioned, or fermented foods that also have probiotics and things like that? It's a great question and a question that I'm being asked very often. I can tell you that what we've been discovering in our own studies, even without looking into the personalization aspect, is that some of the behaviors which your grandmothers would recommend to you are also beneficial in terms of what they do to the microbiome. So, for example, maintaining healthy sleep patterns and avoiding as much as possible erotic sleep weight behavior has very profound effects on our measurement of the microbiome and how it impacts our regulation of weight and glucose or sugar metabolism or the avoidance of type 2 diabetes, for example. In terms of fibers, you know, in general, I think that the data is quite solid in promoting fibers as a good, you know, family of foods to consume. However, I must say that we and others are engaged in very exciting studies, which suggest that even with fibers, not all fibers are created equally. In other words, you know, even fibers are composed of many different chemical formulations that differ from each other in the way that they are consumed by the microbes and impact the human body. So even with fibers and with the generally beneficial effects that have been observed with them, it seems that some fibers are better than others and we're trying to contribute towards new knowledge that would refine these recommendations in different individuals and with different fibers. You know, smoking seems to be a universally bad behavior for many reasons, but when we measure what it does to the microbiome, we were intrigued to find that many cigarette related chemicals not only reach the systemic circulation, but they actually penetrate the gut and they impact the microbiome towards a disturbed composition and function. And this has its own independent effects on, for example, the risk of developing obesity after you attempt to stop smoking. So all of these behaviors, which in many cases we know are probably not good for us, are also not good for us in terms of their effects on the microbiome. Beyond this, I think that we need data, we need knowledge, we need to increasingly learn to harness diet to the individual in order to really optimize the power of the microbiome in impacting human health. And what about the timing of our food intake? Would you say that's a pretty top? I can tell you that in our personalized nutrition, machine learning algorithms, which are used to predict a person's dietary responses in a very accurate manner, the timing of our diet, and even the timing of our meal last night are part of the features that are used by this unbiased algorithm in order to form its very accurate predictions. In other words, it seems that the timing of our diet is important for many different aspects coming from many different studies by us and by others. What we do with it, in addition to trying to time our diet in a kind of normal and routine manner, is still under review or under research. So this algorithm that you were just referring to, so this is a company that was, was it started by you or? Yes. So basically the personalized nutrition project was an ambitious project, which was headed by me and my colleague Aaron Sigal, who is a mathematician from the Weizmann Institute of Science. And we started with this project back in 2012. and this was a study that was first published in 2015 and formed the cornerstone of what we call personalized nutrition today. And in this study, we analyzed the data from a thousand individuals in Israel that kindly gave us a week of their life. And we measured and collected an unprecedented amount of microbiome and host-related data, including a smartphone app that was used in this study and continuous glucose measurements that generated very accurate measurements of sugar responses to food in a week of follow-up. And then a very sophisticated machine learning and AI technologies were used to generate predictive algorithms for each individual that are able to accurately predict a person's sugar responses to any given food. And this eureka moment was the basis for personalized nutrition because it allowed us for the first time to formulate diets that are different between individuals, but would hopefully lead to normalization of blood sugar levels. And this was tested by us in different contexts, including recently in a long-term randomized human trial, which compared this data-driven personalized approach to the gold standard American Diabetes Association recommended diet. And we've quite convincingly showed that this personalized science-driven approach was outperforming the current one-size-fits-all diet in a large group of pre-diabetic individuals, which are individuals already predisposed to develop disturbances leading to type 2 diabetes. set of discoveries has been repeated by other groups across the world and is gaining track and basically tells us that data coming from the host, from the human host, and data coming from the microbiome could be combined using advanced technologies in order to predict and maybe to impact dietary interventions at different clinical contexts. So this company, I know it's called Day2, and does a person have to wear a continuous glucose monitor or like, you know, there's a bunch of biomarkers that need to be done to try this out? Yeah, so that's a great question. And just to make clear to our audience, all the research that I've stated was academically done in an academic setting without any company involved. But following the publication, the Weizmann Institute of Science have licensed the technology to a spin-off company called Day2, which further developed it for massive use in upscaling by many more individuals. What the advantage is of day two as a company is that now that they've performed over 100,000 tests on 100,000 people and more, the quality of data that was collected is so great and the resolution is so great that the people that are now engaged no longer need to go through all the procedures that characterize the early studies and they don't even need to wear our continuous growth as monitor anymore. In other words, a person can now provide a stool sample that can be shipped through the mail, plus some commonly available clinical parameters that they can provide through the internet, and then an accurate prediction of that person's glycemic responses or sugar responses to foods and recommendations that are peculiar and specific for that person could be provided because of the background database that was already created. Now, I'm not part of the company. I'm one of the two scientific founders of the company, but the company is now running on its own, mainly in the U.S. and is available in the in the US. And the findings that we discovered have been reproduced by others in other human studies in the UK and in the US. There are other commercial entities that are developing the same approaches. I can tell you that in the book we published called The Personalized Diet, in addition to our story, we also describe a kind of a do-it-yourself, a non-commercial way to exploit these discoveries. For example, by buying a glucose monitor that you can purchase in your local pharmacy and by skin-pricking yourself and measuring your blood sugar responses after some of the foods that you usually consume at your daily lives, you can now start to tweak your diet and to change ingredients in your diet in reducing your sugar responses after meals. So you can do it yourself in, of course, much less sophisticated manner, but you can use the same principles that we've discovered in changing elements in your diet and making your sugar responses lower than before. So it sounds like you're a proponent of people wearing a continuous glucose monitor. I've worn one for the past, oh, almost three years. And I have learned an immense amount of very interesting information from wearing one. Probably one of the most surprising ones early on, I started wearing it when I was a new mother, and was the effect of lack of sleep on how the way my body responded to the same foods that I've always eaten in terms of my postprandial glucose response. And it was completely out of control when I was...when my sleep was disrupted. You know, there are people that...there are scientists and researchers out there and physicians that do not like the continuous monitor, you know, glucose wearing approach because they claim that it, you know, urges people to not eat a healthy fruit or something like that because it may elevate their blood glucose level. What do you think? Well, I'm not sure I would like to propose that every person wears a continuous glucose monitor, but I respectfully disagree with those who say that, you know, measuring yourself or using science and technology in order to improve, you know, what you do in your daily lives would, you know, be wrong. I think that, you know, disregarding all the advances that science is proposing to us and not utilizing these advances for our benefit would probably make us miss a lot of the good that science has to offer. So by, you know, by wearing a continuous glucose monitor, you probably experienced many surprises and maybe, you know, we've done thousands of people and I can tell you that almost in any person that we've measured, we found counterintuitive surprises. Some people spike their blood sugar to the roof when they eat tomatoes. Now you combine tomatoes with some white bread and the response goes down. So, you know, by not doing the experiment or by not measuring themselves, they would devoid themselves from the benefits of knowing what is good and what is less good for themselves. So I'm all for measurement. I'm all for knowing and for doing this rationally and carefully, but doing it. I'm in 100% agreement with you. So your book is the personalized diet. You co-wrote it with your collaborator, Dr. Aaron Sengal. Seagal. Oh, Seagal? Yes. Okay. And Day 2, which is now licensed by the Weitzman Institute for Science, is the app you were talking about. But again, thank you for talking about the alternative approach with perhaps even people getting a continuous glucose monitor. If people want to follow you, you're on Twitter. Your Twitter handle is elinav underscore lab. So that would be E-L-I-N-A-V underscore lab, L-A-B. And you also have two lab websites. If you Google your name, Ilan, E-L-A-N. Yes, Ilanov, I-L, sorry, E-L-I-N-A-V. You'll find all the lab research that you're doing. Phenomenal, I mean, amazing impact that your research has had on our understanding of the interaction between the microbiome and in our gut and human health. And I'm so happy that we were able to connect and have a conversation today. I've been a big fan of your research for a long time now. So thank you so much for coming on the podcast and taking time to have this very interesting discussion with me."

Cgm: Benefits

set of discoveries has been repeated by other groups across the world and is gaining track and basically tells us that data coming from the host, from the human host, and data coming from the...

"It's my absolute pleasure and great talking to you, Rhonda. Thanks again to Dr. Iran Alanov for joining me all the way from Tel Aviv, Israel for our latest expert interview. And thanks to our listeners for tuning in. If you're looking to quickly learn more or dive deeper into the science on metabolism, brain aging, time-restricted eating, an analytical dissection on the best healthspan promoting practices and more, you will probably enjoy our premium podcast, The Aliquot. Each episode is short and focused on a single topic, curated and remixed from the best of our longer form videos, interviews, and members-only Q&A sessions, dozens of which are now found along with comprehensive notes right on our members dashboard. I also do monthly Q&As, which go out on the Aliquot as well. We also send out a bi-monthly science digest where we summarize science stories that I think you should know about. And there's more. These all add up to a really great membership experience and it helps me to make this podcast, including the free one, one of the best resources it can possibly be for the wider health and aging community, all while getting some cool resources that wouldn't otherwise exist. It's a good deal. You can try out the premium membership for 30 days. Find that at foundmyfitness.com forward slash trial. That's foundmyfitness.com forward slash T-R-I-A-L, trial. Thanks for listening and talk to you very soon."