In this episode, we talk with Dr Justin Sonnenburg, Professor of Microbiology and Immunology at Stanford University. He is a leading expert in the field of gut microbiota and has made significant contributions to understanding how they impact human health. We will discuss the structure of the gut microbiome and microbiota variability, and how these can change in response to diet and environment. We will explore the early establishment of your microbiome and how your mode of delivery into the world (C-section or not) shapes your gut. Our discussion also includes lifestyle factors that can alter your microbiome and the integral role the gut microbiome plays in communicating to other organs, including your brain.
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Ruth Adewuya, MD: Hello, you are listening to Stanford Medcast, Stanford CME Podcast where we bring you insights from the world's leading physicians and scientists. This podcast is available on Apple Podcast, Amazon Music, Spotify, Google Podcast, and Stitcher. If you're new here, consider subscribing to listen to more free episodes coming your way.
I am your host, Dr Ruth Adewuya. This episode is part of our Hot Topics mini-series, and today I will be chatting with Dr Justin Sonnenburg on the important topic of gut health and debunking some myths. Dr Justin Sonnenburg is a microbiome researcher and professor in the Department of Microbiology and Immunology at Stanford University's School of Medicine.
He is a leading expert in the field of gut microbiota and has made significant contributions to understanding how they impact human health. He is a recipient of several awards for his research, including the NIH Director's Pioneer Award and the Burroughs Wellcome Fund Investigators in the Pathogenesis of Infectious Disease Award. He is also the author of the Good Gut and Gut Reaction Books, centering on Microbiome Health, co-written with his wife, Erica Sonnenburg. Thank you so much for chatting with me today.
Justin L. Sonnenburg, PhD: Wonderful to be with you, Ruth. Thanks for the invitation.
Adewuya: Let's start with terminology. What is the microbiome?
Sonnenburg: The microbiome is a complex community of microbes. The microbiome that we study is in the digestive tract. It's a complex community of microbes that lives in the gut and we have microbiomes all over our bodies, on our skin, in our nose. We are constantly experiencing microbes in the environment, but the gut microbiome is really the community of microbes that is fundamental to our health.
Adewuya: Specifically talking about the gut microbiome, can you talk about where does it come from? Is this something that is part of when a baby's born? Does a baby have a microbiome already? Can you talk more about that?
Sonnenburg: When we're in the womb as a fetus, we're actually sterile. We don't have microbes associated with our bodies and certainly not in our digestive tract. And then as soon as we're born, we're rapidly colonized by a bunch of species. We're like a new ecosystem. And so the first microbes we experience are typically derived from our mother and the environment that we're born into.
Babies are colonized if they're born through vaginal birth with vaginal microbes, microbes from their mother's stool, and then their skin also are covered with the microbes from the mother. It's interesting actually, C-section babies are first colonized by microbes that appear to come from skin rather than from the birth canal. And then over the ensuing weeks, months, years, we undergo a microbiome assembly process.
These microbes keep assembling our growing ecosystem. Many things can impact the species that come. Things like breastfeeding versus formula, whether you own a pet, just exposure to different things in the environment, whether you take medications like antibiotics, all of these things can impact the development of your gut microbiome. And then throughout life, diverse factors can shape this community because species can come and species can go and taking medications like antibiotics, what diet you eat, whether you travel, are all big factors, but it's all part of this process of having this malleable component of our biology.
Adewuya: Thank you so much for that overview. I think that's very helpful because one of the things that I heard from you is that it's very flexible and there are many things that impact the development of what our individual microbiome looks like. And so from your perspective and from the research that you've done, what is a healthy microbiome?
Sonnenburg: Yeah, that is a million-dollar question. It really has turned out to be a very difficult question to answer because a microbiome is highly individualized and what is healthy for one person may not be as healthy for another person, although there are some rules that are emerging. I would say that going back 15 years now, the Human Microbiome Project launched by the National Institutes of Health was a really important step at understanding what microbes inhabit the human body in different places, including the gut.
One of the goals of that project was to try to define what a healthy microbiota is. And I think one of the things that's become clear is not only is that a difficult question, but we assumed at the beginning that we could define the microbiome of healthy people and have an idea of what a healthy microbiome looks like. And what we're coming to understand is that the microbiome of healthy people living in the industrialized world may actually be a somewhat deteriorated gut microbiota.
It may be a community that has experienced just a lot of insults through our lifestyle and medical practices, and that the microbiota that exists in a healthy industrialized person may actually be a microbiota that's predisposing us to different western diseases. So we're starting to get an idea of what a healthy microbiota is, what a microbiota looks like in different disease states, but it is a really complex topic just because of the individuality and context.
Adewuya: What I heard from you there is that you can't just paint this brush and say this is what healthy looks like. You mentioned the Human Microbiome Project. Can you just talk about that a little bit? What is that project?
Sonnenburg: That was a wonderful project that the Institutes of Health started in like 2008 or so. There was growing recognition at that point that we had known for a long time that we have microbes living all over our bodies, but there really was large body of emerging evidence in the field that these microbes are just fundamental to our health.
If you change your gut microbiota, you can change your metabolism, you can change your immune system. And I think there's some really exciting implications there for how we might use this community because it's malleable to actually shape our biology in beneficial ways, both to treat and prevent disease. But at the time that the NIH started the Human Microbiome Project, it was basically an effort to just map the microbes that are present in an non-human.
And a large portion of that effort was turning the wonderful sequencing technology that had been developed and grown for sequencing the human genome which had been completed, turning that technology towards our gut microbes and using this sequencing technology to better define this community. And so all of that effort really laid a fabulous foundation for the field for investigators to start digging into more of the biology and understanding the fundamental connections between these microbes and our health.
Adewuya: That's excellent. It sounds really fascinating and important work as well. And I'm curious to learn a little bit more about your story and how did you get into this world of gut health research, gut microbiome? What inspired you to pursue this field of study?
Sonnenburg: I was a PhD student and I had recently married my current wife. We met in graduate school and we were both looking for post-doctoral fellowships and looking to move into a field that had a lot of open questions that a lot wasn't known about and presented, but career's worth of opportunity for studying, solving intriguing biological puzzles.
And the gut microbiome just seemed to be perfect for this. It was a time where there was really not a lot of literature. There were a handful of really beautiful tantalizing publications at that point suggesting this was going to be an important area, but mostly just this big complex microbial community with very little known about it. And so we at that point, were lucky enough to get positions in Jeffrey Gordon's Lab at Washington University in St Louis.
And we moved there in 2003 again when the field was still relatively small. And then over the course of the following five years of our post-doctoral fellowships, the gut microbiome space and human microbiome, human associated microbes really came to the forefront of this new kind of biomedical revolution where there was just increasing understanding of the importance of these microbes in human health. And so we found ourselves thrown from a relatively simple backwater, interesting biological question to this really important new thing in biomedicine. And that was a pretty exciting position to be in.
Adewuya: Yeah, it sounds really exciting. And how cool is it to be on the forefront when it wasn't a thing yet and when it was just interesting and it was on the cusp. And I know we'll talk about your research a little bit more later, but already being part of the groundwork of all of the amazing work that is happening here, and in fact this in the gut microbiome has also expanded to the public.
And social media and a lot of conversation is happening, a lot of fads are happening, a lot of do this, don't do this, eat this. So my next couple of questions for you are like a little bit of myth busting. Let's talk about these fads and want to hear from the expert what your thoughts are on this. So the first one is fermented foods like kombucha and kimchi, it's gained a lot of popularity in recent years. Can you talk a little bit about what role do fermented foods play in gut health?
Sonnenburg: I think one of the things that we've noticed with the industrialized microbiota is that it has lost diversity. We've lost species that were part of our evolutionary history. And because we are a composite organism that has microbial and human parts that need to work together. So it's almost like a genetic knockout experiment, but instead of losing parts of the human genome, we're losing part of our composite microbial genome.
And the question is, how important is this? And we think this may be important in driving, for instance, the inflammation that underlies chronic inflammatory diseases such as metabolic syndrome and autoimmune diseases and so forth. But I think a major question in the field is how can we tune our gut microbiome to be healthier? Can we do this through diet? Can we bring back microbes or foster more diversity that would make us healthier? And fermented foods are really attractive from the standpoint of them harboring live microbes.
And it just being this obvious connection that for lacking microbes in our digestive tract, maybe if we were to consume foods that have been transformed through fermentation, we would be able to compliment back some diversity in our gut microbiome that's been lost. And of course, the microbes in fermented foods are different than the microbes that exist in our gut, but still there may be a role for them to play.
And so we actually performed a study at Stanford in collaboration with Christopher Gardner's group, their wonderful partners and performed dietary interventions. And their group actually had people eat diverse fermented foods, things like kombucha, kimchi, kefir, miso, just a broad array of fermented foods over the course of a six-week intervention. And prior to that, there was a four-week ramp period, so it was about 10 weeks of eating fermented foods.
And what we saw over that period in monitoring these people's microbiome and immune systems, so by drawing their blood throughout the course of the study, we saw that these people increased microbiome diversity, so exactly the signature you would hope to see in trying to foster a healthier gut.
And then we also saw that many inflammatory markers decreased over the course of that intervention. And so it really appeared like the fermented foods were playing an important role in fostering a healthier microbiome and a healthier immune system. Now it leads to this big question of what are the aspects of the fermented foods that are leading to these changes in human microbial biology and our immune system? It turns out that the microbes in the fermented foods are not responsible for the increase in diversity directly.
There's something in the fermented foods that's leading to acquisition of actually gut resident species. So there's some interesting more complex mechanism to diversity acquisition. But we also know that fermented foods have lower glycemic index because the microbes in fermenting the foods have consumed a lot of the simple carbohydrates. We also know that there's a lot of interesting chemicals, metabolites that are produced by microbes when they're fermenting foods.
So there's this whole array of candidates for what it could be about the fermented foods that's positively impacting our health. And in follow up experiments in mice and a lot of other data in the field, it appears that it may be the metabolites that are playing a large role in this. It may be the chemicals that the microbes are producing, things like lactic acid when you make yogurt or when you make sauerkraut, the microbes in there are making a bunch of lactic acid out of the simple sugars. And it could be that those metabolites are what are actually key mediators of these health benefits of fermented foods.
Adewuya: So it sounds to me that is it a fad maybe? But it seems like there's positive aspects from patients or people taking in fermented foods. It may not be the fermented foods itself, but there's something about that process that could lead to positive change in terms of a healthy microbiome. So I think if I had to vote, I think it will be like we're in the middle fad or not. I think maybe, right.
Sonnenburg: I think that's worth reiterating here is that when moving from fad to something that has really solid scientific evidence, there's a total transition phase. And in some cases, the fads will be debunked and will find out that they don't do anything or do bad things or do different things than we expected. In some cases, we'll find out that some of the good things are reinforced and scientifically validated.
And I would say with fermented foods, we're somewhere in between right now. Our study, it was a really rigorous study, but it was a small study and it was on healthy adults, and this needs to be extended into other populations and replicated by other groups. We need to understand dosage. We need to understand what types of fermented foods are better than other in which people. So there's a lot of additional questions to ask. And I would say that fermented foods are the point of transitioning from fat into something where there's some evidence, but we need a lot more evidence before it should be written into the guidelines of what everybody should be doing.
Adewuya: That's excellent. All right. Next fad for you is prebiotics and probiotics. Prebiotics and probiotics are often viewed across social media as the ultimate gut health solution. The science behind them sounds to be a little complex. Can you talk about some of the latest findings around prebiotic and probiotic research and do they support this buzz that we're hearing?
Sonnenburg: Yeah, this is excellent. Prebiotics and probiotics, the sales year-over-year go up. Obviously people are paying attention and spending money on these just to get the definitions clear. So prebiotics are the compounds quite often, like purified forms of dietary fibers, so complex carbohydrates that we can't digest that feed our resident gut microbes. And it makes sense that these would be thought to be beneficial because one of the things about the industrialized diet is that it's very low in dietary fiber, and we know that dietary fiber is overall associated with health.
And then also from a lot of mechanistic studies in the gut microbiome, one of the major fuels that feeds our gut microbes and drives beneficial metabolism in our gut microbiota. So because the western diet is so deficient in dietary fiber, prebiotics, purified forms of dietary fiber are thought to be one way of supplementing back something important that's missing from our diet.
Probiotics are live microbes that you can take when pill forms, sometimes they're found in added back to yogurts, but they're typically taken as supplements and quite often are derived from fermented foods. So you could think about probiotics as being like a sub-component, quite often of fermented foods that are packaged in pill form that we can take. And there's a huge attractive element to supplements as a way to improve gut health because we've shown in the field over and over again that it's really hard to get people to change their diet.
I think the evidence right now suggests that eating a healthy diet, plant-based diet, high fiber, limiting red meat consumption, limiting saturated fat, keeping simple carbohydrates, low glycemic, all of these things are really beneficial for health, but difficult to get people to do not only because of all the processed food that is easy to access, but also just because as humans, we all crave sugar and fat and salt, and it's really difficult to fight these cravings when we're faced with panel of different foods to try.
And so supplements are attractive from the standpoint of a simple way to perhaps improve what we're sending down to our gut microbes. I would say that the data right now is very sparse in terms of the benefits of prebiotics and probiotics. Certainly the data is nowhere equivalent to the benefits that we see with a healthy diet on human health. And so the additional complication is that the supplement industry is regulated.
It's not closer regulated by a external bodies. And so quite often probiotics will be you just buy in the supplement store can be contaminated with other microbes. Prebiotics are again, not really well regulated, and these are just areas where there's not a lot of evidence that they do a lot of good. And it doesn't mean that people can't find supplements out there that aren't good quality and aren't helping them in some way. So people should definitely try and if they find something that works for them, that's great, but it's just a situation of buyer beware that we don't have a lot of great data yet. And there are a lot of complications with regulation of this supplement side.
Adewuya: This seems to fit more in the fad lane right now, prebiotics and probiotics. If people can find something that works for them, then they should explore that. But what are the actual markers that it's actually working?
Sonnenburg: Yeah, this is very difficult for people to assess. What you would want with something that others at Stanford have been working on with immune monitoring, trying to have assays or tests where you could go into the doctor and say, "Doc, how is my immune system doing?" And if you could do that repeatedly while tinkering with your gut health and maybe tinkering with different diets or supplements, you may get a sense of what is leading to a less inflammatory state.
And then the other thing that people pay close attention to is stool consistency and digestive symptoms. All of these things as scale your bowel habits. I think all of these things are important readouts of your gut health, but I think your question points to a big gap in the field right now, which is how do we get more information?
Adewuya: Excellent. The last kind of fad-ish topic that I wanted to bring up is the connection between gut health and mental health. I think the conversation around mental health has been surfaced a lot. I think the pandemic even surfaced that for a lot of people. And now there's this conversation around gut health and mental health. Is there some kind of interrelatedness to this?
Sonnenburg: It's a really interesting and complex area that we're just right at the beginning of understanding. I think it's really exciting time again because of the foundation that's been laid in the field that these microbes in our gut are making chemicals that get absorbed into our bloodstream traffic throughout our body can cross the blood-brain barrier, can impact our central nervous system.
There's nerves that connect our gut to our brain. There are immune system cells that get located to the gut and then they start cycling around the body and can relocate to different areas. So there's lots of ways that things that happen in the gut can impact our central nervous system. We know just inflammatory level can impact what's happening in the brain. And so there definitely are these connections. There have been experiments in animal models clearly showing that you can change behavior of mice, you can change rates of neurodegeneration just by changing what's happening in the gut microbiome, what species are there and what those species are doing.
So I think there's great promise for addressing a lot of these issues through changing the gut microbiome. But one of the difficult aspects, which is implied in your question is that this is a bidirectional interaction that everything that's happening on the host side that the microbes are influencing feeds back and impacts the gut microbes. And so we end up in these self-reinforcing states that are, in some cases disease states, whether it's something that's like anxiety or something that is like inflammatory bowel disease.
And those states are very difficult to escape because of the reinforcement and feedback mechanisms. And so there will be, I think a huge growth of understanding in this area over the coming decade. But because the gut microbiome is so complex and so individualized and the central nervous system is so complex and something that we're just starting to grasp how it functions, it's going to be a little wild before we really have a great understanding of how these two complex entities interact within an individual.
Adewuya: That sounds like to be determined what the impact of the gut health through mental health. You wrote a book with your wife called The Good Gut, which has of course been a popular resource both for clinicians, for patients that are interested in gut health. And you cover a lot of things in that book. You talk about the microbiota and some of what we talked about today. You also talk about should we consider alternatives to antibiotics, but synthesize some of the key takeaways from your book and how they may be applied to clinical practice?
Sonnenburg: Absolutely. And I should just reiterate from your introduction that I'm not a medical doctor, I have a PhD. The motivation for writing that book, Erica, my wife and I, as we were researching the gut microbiome, we realized we were changing our lifestyle in really fundamental ways. We were changing our diet. We had two young daughters at that time. We were changing how we were raising them. There was just really a lot that we were translating from this basic research we were doing into our lives. And the reason that we were doing that is because the side effects or the cost, if we happened to be wrong in some of this translation, didn't really seem to be bad. All the changes we were making were consistent with kind of nonmicrobiota research, what other research was pointing to for healthy changes in your life. And so the microbiome work really reinforced it.
And then we realized that none of our friends, family members were doing the same things that we were doing until we'd go to a conference that was focused on the gut microbiome. And then all of our friends and colleagues were doing all of the same things with their lifestyle. And it really suggested to us that there was this privileged access to information for people in the field, and we wanted to democratize that information in some way and make it available to other people, talk about our own personal journey, but put that in the context of the science that is unfolding in this area.
And so that was really the motivation for that book. But to distill out the big messages there, if you're in a healthy state, it's a great time to really embrace changing your gut microbiome, to reinforce that healthy state. Things like a plant-based diet full of dietary fiber, doing that habitually over a long period of time suggest that you'll be able to recruit new members to your gut microbiome that are good at degrading fiber, producing healthy metabolites like short chain fatty acids that can educate your immune system in beneficial ways and reinforce your colonic barrier, incorporating fermented foods and just incorporating environmental exposure to microbes.
And then the antibiotic issue is really interesting. I think antibiotics are incredible. Drugs, really important in the right situation have saved countless lives. I take antibiotics when it feels like the time is right, but I'm also very careful after I take antibiotics to eat properly and try to nurture back a healthy microbiome. So just being aware that you have a gut microbiome that's important to your health can help you be aware of the decisions that you're making. And now we have to understand there's this trade off. There are bad microbes and there are good microbes that are fundamental to our health, and we just need to live our lives in a way that recognize the importance of that microbial biology that's so important to our health.
Adewuya: I like what you said about finding the balance between everything that we do. Can you talk about some of your specific dietary recommendations that you might have for patients that are looking to improve their gut health?
Sonnenburg: One of the things that's become apparent is going slowly and making changes that are sustainable for your lifestyle is super important. I think changing things very suddenly not only makes it very difficult from the standpoint of making something habitual and something that can be continued in your life over a sustained period of time, but I also think that your gut microbiome needs time to adjust to new things. Gut microbes don't do well with sudden changes. You end up with a lot of digestive distress. And so even in our studies, we have what we call ramp periods where we gradually increase dietary fiber or fermented foods or ween people onto a Mediterranean diet. The dietary intervention is we have a ramp period as a period where people can slowly incorporate the changes in their diet. Lifestyle is the same way. If you want to go outside and garden, you shouldn't put in a 40 acre plot on your first try.
You should start with a few garden boxes or something like that. I think the big picture is as you learn about this field is for you or your patients to understand that it's a journey. It's been 15 years. I'm still changing my lifestyle over time to try to adhere to the principles that I know a little bit better, but also to incorporate new things is find them out and think that they're scientifically solid. I will say that I think the two single most important things that you can do for your gut microbiome are increase complex carbohydrates through plant-based eating. And even Christopher Gardner, the wonderful professor that we do the dietary interventions with who specialty is diet, talks about the one rule diet. The fact that if you're eating a lot of plants and you do that first at every meal, you basically don't need to know anything else for nutrition and for your gut microbiome.
Or you can not have a perfect diet, you can have little indulgences, but if you're mostly eating plants and you use that, that creates satiety, that feeds your gut microbiome and provides a lot of other nutrients that are super important for your health. I think limiting antibiotic use is another important one. And I would say that the key there is to make sure that you don't push things to the point of it being dangerous. You just have that conversation with your patients, or if you're talking with a physician, just have the conversation and say, "Do you think it'd be okay to wait another day or two and see if this starts to resolve on its own?" If that doesn't feel safe to your physician, you should probably listen to them. You can work on fostering back a healthy microbiome if you take antibiotics.
Adewuya: What I'm hearing is that for the clinician patient relationship, that at least there should be a conversation about it. For the clinician, part of it is awareness themselves to be able to have important conversations with patients. I'm wondering if you have engaged in this research with other medical professionals and what has the response been to some of these concepts and incorporating this into how they care for their patients?
Sonnenburg: This super interesting question, and I've engaged with physicians quite a bit on this. I hear a range of responses. Some physicians refuse to use diet as one of the major tools, even though they know it would be powerful because they say that it's so difficult to get people to change their diet. And understanding of nutrition across the population is so poor that it would just take way too long to try to educate people about what they should be eating. And we have such a good understanding of the powerful drugs that are at our disposal. It's just a much more feasible way to deal with medical conditions. And so it's one of these issues that I think is a problem with the system and how it's set up. And we've set medicine up to be reactive to specific diseases. And that was born out of the air of infectious diseases where we had to wait for somebody to get sick before we could treat it.
And I think now in the era of chronic inflammatory diseases, we need to remake our medical system in a way that we can prevent these diseases. And I think changing our diet to foster a healthy microbiome is a great way to do that. I've talked to physicians at the other end of the spectrum that are using diet in the clinic and having incredible success. The problem is that these appointments with patients take an hour to dig into what their issues are, what the sticking points are, what food means to them culturally, what's comfort to them.
Food is just so tied to our identity and it's a place that we go quite often for comfort and feeling home and family and so forth. And so I think getting people to remake their diet is a really big endeavor. It's a worthwhile one. The physicians that are taking the time to do it, I know are having tremendous success, GI symptoms, resolving that have plagued people for a long period of time, but it requires a huge investment from the physician's side.
Adewuya: Yeah, I hear what you're saying about how our systems are set up, whether it's in the care perspective, how our hospitals, how our clinics are set up. I think it's also in education, how much time is in the medical school curriculum to talk about nutrition and diet and to empower new physicians to include that as part of their care portfolio. And probably has something to do with insurance and billing and how much time you can spend with a patient. So it sounds like it's such a multifactorial piece, but also for clinicians, it's encouraging to hear that if you do take the time, if you do have these high level things that you can share with your patient, you might not be able to spend an hour, but you might be able to just move the needle along that one time.
Sonnenburg: Exactly. And if you have repeated interactions, just chipping away at it at each one of those appointments, I think is a great way to think about it.
Adewuya: Looking to the future of this exciting field, it sounds like there's a lot more to unpack around gut health, microbiome. What's keeping you excited about this field that you're currently researching or others in the field are researching?
Sonnenburg: The field is poised right now for really big things. It's really exciting. The fact that the microbiome is connected to so much of our health. The fact that it looks like most of us have a somewhat deteriorated gut microbiome, and the fact that it's malleable means that we can improve it and we can probably reap huge gains in terms of treatment and prevention of diseases. So I think we're on the cusp of really big things for the gut microbiome. It's super exciting. I would say that fecal transplants may be something that a lot of people have heard about out there. It's a way of kind of rebooting a diseased gut microbiome, installing a new microbiome from a healthy donor that this can cure things like chronic C difficile Colitis. It's a fairly crude treatment. It's very effective. Huge cure rates for C diff with fecal microbiota transplant.
But the phase two of this will be microbial therapeutics, complex consortia of microbes, cocktails of microbes that are defined and applied. You could imagine if you're suffering from C diff, instead of having a fecal transplant taking a cocktail of 20, 30, 40 different microbes that have been tested or equivalent to a drug, but basically fostering a new microbial community. So I think there's going to be this whole new era of microbiome-based therapies coupled to a lot of information about just how people can foster a healthier microbiome in their own life. And I think the compliment of those two aspects, the medical aspect and kind of what people can do at home is going to lead to just overall better health in the population. And so I'm really excited about the next five to 10 years.
Adewuya: That's very exciting to hear, and I'm looking forward to learning more and hearing what's happening in this field. Thank you so much. This was such a great conversation. Very informative for me personally, and I know that it will be very informative to our listeners.
Sonnenburg: Wonderful to be with you, Ruth. Thanks so much.
Adewuya: Thanks for tuning in. This episode was brought to you by Stanford CME. To claim CME for listening to this episode, click on the claim CME link below or visit medcast.stanford.edu. Check back for new episodes by subscribing to Stanford Medcast wherever you listen to podcast.
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Ruth Adewuya, MD, CHCP
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