Victoria Maizes: Hi Andy.

Andrew Weil: Hi Victoria!

Victoria Maizes: Today we have a chance to speak with a leading microbiome researcher, Dr. Suzanne Devkota.

Andrew Weil: Well, microbiome is a very hot topic, and I believe we've heard her before, so I'm interested to hear what she has to say now.

Victoria Maizes: You know, before psychedelics became such a hot topic, I feel like it's what people ask you most about.

Victoria Maizes: Let's get her on.

Andrew Weil: Okay.

Victoria Maizes: Dr. Suzanne Devkota is an Associate Professor of Medicine, and serves as the Director of Microbiome Research at Cedars-Sinai Medical Center in Los Angeles. She earned her doctorate at the University of Chicago. In molecular metabolism and nutrition.

Dr. Devkota is currently investigating the role of the gut microbiome in inflammatory and metabolic diseases, and the role that microbes play when selective pressures make them pathogenic welcome, Suzanne.

Suzanne Devkota: Thank you for having me.

Victoria Maizes: We're so delighted, and I have a big ask for you. I'd like you to give a brief introduction about where science stands right now about the influence of the microbiome on health.

Suzanne Devkota: Gosh!

Andrew Weil: That’s a big question, Victoria.

Victoria Maizes: I know

Suzanne Devkota: Absolutely. Yeah. I mean, it's this field that just it's been growing at an exponential pace, and it evolves year to year People have been investigating the microbiome, not just the gut microbiome, but skin microbiomes, oral microbiomes, and so on and the relation to almost any disease you can think of. Now, whether the microbiome is truly involved in the genesis of these diseases is still a question. But there's certainly some conditions where it's pretty unrefutable at this point, and so I would say, the vast majority of individuals in the microbiome space studying human microbiome study the gut microbiome.

And because that's the largest density of microbes in our body. And so gastrointestinal diseases and conditions like IBS and functional bowel issues are the most closely linked to the factors related to the gut microbiome but what components exactly is still very much in progress in terms of our knowledge. And a lot of this has been derived from my from animal studies. And there have been, you know, some good human studies, too, but I think the animal studies have really demonstrated how important the gut microbiome is to GI diseases. And so that's really come from these animal models that we have that are germ free mice that are actually raised from birth with no microbes. And so that's a very powerful tool for understanding what physiology and biology does when you have no microbes from birth, and they don't die so they don't need the microbes to live. But they're also in a completely sterile, isolated environment which is not our world.

As soon as you take them and you put them into a non-sterile environment, they get very sick and inflamed without their microbiome. So disease, susceptibility models, they're mice that can sort of mimic some aspects of Crohn's disease or ulcerative colitis.

They don't develop those diseases in the absence of a gut microbiome in the germ-free system. But when you put bugs back they start to get flares so to speak. So those studies have really kind of shown us that for GI diseases microbes are involved. There's also been studies in some metabolic conditions where people will get antibiotics, and they see resolution of metabolic syndrome, like like things related to maybe glucose excursions and obesity and things like that. But you know it's the mouse is not the human. And so when we look at humans, it's it's much trickier, because every human has a different microbiome. And so it's what do you pin, you know, cause and effect on? And that's been the big challenge. But I think still, even in humans, it's very well accepted. Certainly in the clinical, inflammatory bowel diseases, space, and in gastroenterology the microbiome is a critical component, and it's usually multifactorial, related to Yyur genetics, your environment your lifestyle what you eat, how you conduct your day to day all those play together. When you start going further afield from the gut, and you start talking about neurological disorders and depression, it starts to get a little more tenuous because our models are not as good to study those outside of the human. So I would say, for neurodegenerative diseases, there's a lot more compelling data coming out now they can actually tie to certain mechanisms. I would say things that are more behavioral are much harder to really tie to a cause and effect to the microbiome.

I would say anything related to the gi tract. So that's even liver conditions, right? Which is part of the Gi tract, biliary conditions. All of those have a pretty strong link to the microbiome. The further out you go from the gut. It starts to get a little harder to prove that. But there's certainly compelling associations. So the field is really still at the stage of associations

Andrew Weil: Can you change your gut microbiome.

Suzanne Devkota: You can. Yes, and unlike our genes, which we cannot change, we can change our microbiome. How we do it, though, is very individualized. And I think that's where we get stuck, because I think people still want a black and white thing that they can do to change their gut microbiome. And the reality is a little more variable than that, and requires people to really pay attention to their bodies and listen to what foods agree and don't agree, and things like that but you can largely through diet. That's probably the biggest way you can. You can shape your gut microbiome. Aside from obviously antibiotics which we want to avoid as much as possible. So diet. And there's also compelling evidence around social behavior in shaping our microbiome, and those are comparative studies from looking at more communal populations. Tribal populations around the world compared to our Western, more isolated, eat it in our car type of lifestyle, and the more we share our environments, the more we share our microbes, and that can be a good thing in many situations.

Victoria Maizes: I know one of your areas of research is looking at dietary interventions to see how they influence the microbiome. And I know our listeners are interested in what have you found what helps people have the healthiest possible microbiome, knowing that we still don't even know exactly what that is.

Suzanne Devkota: Yeah, exactly, you're right. This is like the number one question I get asked dietary fiber which is not sexy admittedly, but dietary fiber is so important, not just for keeping things moving, which just having a regular bowel movement and regular bowel movement pattern when you don't have that, it causes so many issues backing up in the gut. And really you need to keep things flowing. Because when you have stasis really, things that don't move in the gut, that's when you get bloating. That's when you get not just constipation, but all the gases, all the microbes they just start becoming like hyperactive in that area. So things need to keep moving to also keep your microbiome from building up in parts of the gut where they shouldn't belong.

Suzanne Devkota: So but then, beyond just the motility aspect. You know the movement aspect of fiber. There's certain fibers, because [Video 2: Not All Dietary Fiber is Created Equal] not all fibers are created equal. There are certain fibers that microbes specifically can access that we cannot digest. But microbes can access and digest, and by using the fiber as a nutritional source for certain gut microbes, they then produce what are called short chain fatty acids. They're probably the most studied byproduct of the gut microbiome, but it's acetate, propionate, and butyrate, and these are made by the gut microbiome. Certain species from fibers, and your gut lining, your gut epithelial cells directly use short chain fatty acids as an energy source and it helps maintain the gut barrier. So if you hear about things like leaky gut, which is a very sort of loose term for a lot of things, but you can prevent sort of barrier leakage by promoting. You know, these bacteria that produce short chain fatty acids. So fiber is really important, both structurally, functionally, and also for supporting gut microbes that make beneficial products for for us.

Suzanne Devkota: So fiber. Yes, and what I would when people say, What kind of fiber should I eat? I say, really, you know, you want to make sure you're eating a diversity of fiber. So you're going to hear me talk a lot about diversity, because that's really key. So you might have your psyllium husk right like in a Metamucil. But you may also have resistant starches, like in green bananas, for example, those are really good for the gut microbiome, whereas psyllium husk is good for the motility aspects, and so, as much diversity of fibers you can incorporate into your diet the better. So that's one thing. The other is going back to this concept of diversity. Eating a very diverse diet is very important. The microbes that reside in our gut are there in response to what we put into our bodies. And so it's very well accepted in the field that the more diversity of microbes that you have in your gut, so the more different microbes that you have is very associated with health. And so in disease states, we see a reduction in diversity, and that's often because you lose a lot of your bugs with inflammation. So you want to have a lot of diversity, because it means that all the different functions of our gut microbiome that we need can be carried out. If you're missing some bugs, you might be missing some functions.

The way to support diversity is by eating a diverse diet, because certain bugs will really respond to maybe beans or legumes, and others will respond to grains, and others will respond to proteins, and so on. And so, if you have, you know, you hear a lot about restrictive diets, you know, carnivore diets. Things like that. Those kind of diets really create a very narrow, non-diverse microbiome, and that's not good for overall health. And there's been really great research looking at specifically, diversity of plants in your diet. I'm not saying to be. You need to be vegetarian or vegan. If you're an omnivore, incorporating as many different types of plants in your diet has been shown to be the biggest driver of diversity.

Victoria Maizes: Some years ago, Christopher Gardner, a researcher at Stanford, published a paper that showed it was good to 1^st promote diversity. He did that with fermented foods, then feed the diverse mix how important do you think it is to go 1st with diversity and then with fiber? In other words. Is there a worry that if you just add fiber, you may be expanding a pathogenic set of microbiota.

Suzanne Devkota: No, because the organisms that utilize fiber are  all pretty important bugs for our gut microbiome. Rarely do you see fiber promoting pathogenic bugs. Pathogens are very good at using other substrates that are elevated in the inflammatory environment, whereas our good microbes that can metabolize fibers are present in steady state, and generally are the beneficial kind, so I don't think fibers will promote pathogenic bugs. But to his point. If you don't have those organisms there. In the first place your fiber may have not much effect, because who's going to use them?

Andrew Weil: How about fermented foods?

Suzanne Devkota: I think fermented foods are fantastic. I've written a lot on fermented foods. It's still a wide open field. It's been very anecdotal. There's actually really cool and interesting data coming out now studying fermented foods specifically by, lactic acid bacteria and the specific pathways that they interact with in the gut. And there was a really neat study last year that came out that showed that the fermented food metabolites interact with the what's called the aerohydrocarbon pathway in the gut, which is an anti-inflammatory pathway. And this group actually showed that they could enrich the upstream metabolite in yogurts. They could actually create an enriched yogurt product with this that you could consume, and would have this beneficial effect. The fermented foods are good because they are rich in the metabolites, the beneficial metabolites that microbes produce. But also they've really been touted as like probiotic foods. Okay, I'm less enthusiastic about them as a probiotic food, because I think as you consume them, you know. I mean, you're never really sure how many are alive, how many are getting where they need to go, and so on. But that food, as it sits in your fridge is a living food, and It's like a bioreactor in a jar. And so you get to consume all those beneficial byproducts. I think that's the most functional, useful part of a fermented food, and those beneficial byproducts can be directly taken up by our bodies, but they can also feed other beneficial bugs. So there's some cross feeding that occurs. So I'm a big proponent of fermented foods.

Andrew Weil: Any comparative studies on populations like Korea, Japan, China, where people eat at every meal. You know, city of fermented foods compared to the West.

Suzanne Devkota: There have been studies like that again. There are associations, you know to pin it on just the fermented food consumption is, you know, it's compelling. And there are trends definitely in these population-based studies with fermented food, consumption and lower outcomes, related to chronic inflammatory diseases. But the challenge with a lot of these population-based and just human diet studies in general in the microbiome spaces. They're not all large population sizes, and they're not always the best controlled studies, but I would say that the data coming out of them is quite compelling, and warrants, us to really dig into this deeper, more mechanistically.

Victoria Maizes: You mentioned metabolites, and one of the mysteries that has been around, and I think is answered by metabolites is how probiotics could have positive outcomes when there's no living organisms. And now just mentioned that in these fermented foods it may not be the organisms. It may be the metabolites. So can you unpack metabolites a little bit.

Suzanne Devkota: Yeah, absolutely. So. Metabolites would kind of fall under the heading of like a postbiotic which people are hearing more and more about In the consumer product space, we hear about prebiotics, probiotics, and more recently, postbiotics. And so let me differentiate those first. So prebiotics we're talking about fiber. So fiber is a prebiotic. So it's anything, any food product that you eat that can promote a certain gut microbe that you already have in your gut. That's beneficial. So that's the feeding, you know, cultivating the garden that's with prebiotics.

Typically those have been described really to just fibers. But I think the definition should be. And I think actually is, much broader. It's really any food product you consume that can shape your microbiome in a beneficial way.

Probiotics we're all familiar with, but these are actually consuming the organism in some form, whether it's a lyophilized, like a dehydrated bug that reactivates in your stomach or a live bug culture yogurt things like that. So it's consuming the bug in the hopes that it will colonize your gut. And you know. Now, seed some beneficial effect and then a postbiotic is consuming directly the byproduct of bacterial metabolism. So what we call metabolites or small molecules that are pumped out just like we breathe.

You know. Breathe out Co2 microbes breathe out things as well. So it's consuming those. But the definition of postbiotics can also be dead bacteria themselves, like cell wall fragments, and that I'm a little unsure about that definition. But that's sort of the official definition of a postbiotic is a dead bacterial preparation.

Victoria Maizes: It sounds very appealing.

Suzanne Devkota: Yeah, I know, I know. So those are the 3 stages of sort of products that people are consuming the metabolites. What's really in the metabolites, meaning the byproducts of things bacteria make and pump out into their gut. So we have all the bugs in our gut are constantly interacting both with our cells. Sometimes they eat our mucus, sometimes they eat something that a neighboring bug produces, and then they produce something so, and those are the metabolites. Metabolites sometimes are simply made for the microbial community, so they're just consumed amongst each other. But that's a good thing. It's like scaffolding. It keeps everyone in their rightful place and doing the thing they need. So it's supportive metabolites can also be produced and taken up by us and go into our bloodstream. And that's been measurable. So microbial metabolites you can measure in the bloodstream, which is pretty compelling. And so that's where a lot of the gut brain research has come from when you start thinking about bacterial products in the blood, and blood is circulating everywhere, including the brain. So that's when in the field, we think about the distant effects of the microbiome outside the gut. It's usually through their metabolites traveling through our bodies. But what has been the big challenge there is. There are many metabolites that we make our bodies make, and microbes make as well so distinguishing structurally, chemically. Often they look exactly the same. So if you did a blood test and you looked, it's sometimes hard to tell if it's made by us or them. And then some metabolites are called the same thing, but they might be structurally different, a microbial form versus what we make. And so you can you can identify that a little more easily. And then there's some things that only microbes make. And so if you see that, you know that's definitely coming from your gut microbiome. And so I'd say when it comes down to it, the compelling aspect about metabolites, and where the field is really excited and I would say, this is probably the future of the microbiome space is because they travel outside the gut and they go into our bloodstream. They go to other organs, and we still have no idea what the dose effect of that is, how much is getting you know how much of these microbial products different organs are seeing and the effects of that. So that's all. Being actively studied right now.

Suzanne Devkota: Yes.

Victoria Maizes: It's so interesting.

Victoria Maizes: one controversy that comes from something you said earlier, which is that each of us has a different microbiome is, what's the value of microbiome testing. And I think when you spoke at our conference some years ago, you said that, if you do it sequentially in the same human being, you potentially could learn a lot. You could see that you're getting more diverse. You could see the balance of different organisms. But it's expensive. And in the let's say, real world of clinical practice that's not done so much. So, where do you think what's the value right now of testing the microbiome in practice.

Suzanne Devkota: Yeah, you hit on all the caveats and all the all the issues that that are out there.

So even when we design a study in humans or even in animals, we never do cross-sectional studies we never. Compare this group to that group at beginning and end and look at differences because there's so much variation. The real information comes from taking one human being, and doing this over many human beings and taking a baseline sample, and over time their response to different interventions, and then, seeing how their microbiome changes in an individual, and that also, statistically, you get a much well better powered study, but using each individual as their own control, is the most powerful way to look at the microbiome. So for us if, as you know, if we're looking at well, I want to know what my microbiome is just taking a single buying one kit and taking it at one time. If you took it in the morning versus the evening, it could be different if you took it today versus yesterday versus tomorrow. It could be different, almost certainly would.

Victoria Maizes: Menstruating women.

Suzanne Devkota: Absolutely. Yeah. Cycles make a difference. Hormones make a difference. Stress makes a difference. Travel makes a difference. So you know what medications you're on, and all so so many external factors, because our gut microbiome is a biosensor or external environment. And so when you think our external environment is really can be variable day to day, you want to take sequential samples to really get a sense. So you either you might see one bug that you may not want that may be viewed as bad, and it's blooming on one day, and you might, you know, get really nervous or freak out, but then it may go back to being suppressed the next day. So, and we see this a lot. So I often recommend that if you're going to do a microbiome test, so what is the value of it? I think just like with any blood test. You should always have a baseline of you and your healthy state, because most people go and get these tests done when something's wrong and when something's wrong you don't know how far it deviated from your normal, and I think everyone has their own normal. And so, knowing what your baseline normal is is very important. I think the microbiome is part of that, that I'm a big advocate of your microbiome profile being part of your, blood workup, and in your medical files. And so having that as a baseline, because inevitably, I mean, I'm sure you both of you see, all the time Gi issues. Everyone has some version of a Gi issue. It's on the rise. It's really become something that's been a leading complaint of people. Or maybe people are just more comfortable talking about it. I don't know but it's it's there's just a lot more especially functional Gi issues. And often it can be tied back to either small intestinal overgrowth of the gut microbiome, which you wouldn't know unless you had a baseline, and now tools for sampling the small bowel have become much more sophisticated and our tools for sampling. So we can actually see these microbes in different parts of the body. The challenge is that the kits that you might buy, you know off the internet and you do at home are going to be stool based and stool based kits will give you an idea of really just your colonic microbiome. But you have a small intestinal microbiome that's very important, too. And if you're experiencing, bloating and ibs like symptoms that will be in your small bowel. And you won't see that really in a stool-based test. So if you're trying to diagnose certain functional issues. Stool tests can be challenging. But if you're trying to get a sense of your microbiome changes over time or just out of your own curiosity. I think everyone should be empowered to know what their gut microbiome is, and I would say, do it when you're healthy and do it once every 6 months, you know, and if you do that over the course of a few years, you'll get a really nice picture of your gut microbial environment and the changes over time, and you can start to do your own experiment on yourself and say, Hey, I changed my diet, or I went from being an omnivore to a vegan. And here's what my microbiome looks like. The change may not signify good or bad, but it's a change, and it's important to know that. And it's really interesting to see that.

Suzanne Devkota: And I also advocate that people in the same household measure their microbiomes. There's a lot of sharing of microbiomes within households. And I think that's really fascinating to see for people who cohabitate, because in this world of fecal transplants the old recommendation was for people who have to have a fecal transplant for something like inflammatory bowel condition or C diff before there were now stool banks, they would say, we want someone who cohabitates with you to be your donor, because their microbiome would be most likely to engraft in your gut, because it's going to be a little more similar. So I think household comparisons are very kind of important, too. But a lot of it is really just at this stage at the “hmmm I'm just curious about my body” I don't know that we can yet use these tests to really diagnose anything.

Victoria Maizes: You know, I want to talk about FMT. The fecal microbiota transplantation. But before you go to that, one of the things I've wondered about? Are we? Are we moving into an era where people should preserve some of their own stool given that they may have to have a surgery and take high doses of antibiotic, or they may get a C diff infection or something else may happen. And then, just the way you know, if you were fortunate enough that you could afford to preserve your umbilical blood for a future emergency, that it might be wise. And and it's much easier really to preserve your own stool than it is your umbilical blood.

Suzanne Devkota: Yeah, yeah, absolutely. It's a really interesting question. This is sort of comes up in conversation now now and again. I think that it's not a bad idea. Okay, but if you are, you know otherwise healthy and you have, you know your Gi function is added, you know, considered healthy. Then you wouldn't know what your profile you'd want to get your microbiome sequence. Get your profile, and then and then banking it. I think the issue is, there's still a lot of ways one can bank a stool sample. And so there's, you know. And how do you do and preserve it. How long is it good for, I mean, are you personally banking it in your? It needs to be like in a minus 80 freezer, really to really preserve. There's certain ways, because when you just if you just take a stool sample and freeze it away, many of the bacteria will die because ice crystals get into the bacterial cell wall and they die. So your stool has to be preserved in a specific way to ensure that when it is thawed out, the bugs are revived and not all dead, and that's very important. So I don't know that individuals should be banking their own stool themselves. But if there is an opportunity, either for research purposes or there's a local stool bank or something like that, where they might be able to do it, I'd say it's not a bad idea perhaps, after you go off on a long course of antibiotics or or things like that. Butthere have also been really a lot of studies showing that your microbiome is pretty resilient, and it comes back.

Suzanne Devkota: for most people it will come back in the way it looked before, and minus the bug you were trying to kill with antibiotics, and then some people, you know, deviate and go somewhere else with their microbiome after antibiotics. And it's not necessarily a bad, new, normal, but it's, you know it does rebound. So I think the idea that we have to you know force recolonization of our microbiome after after we've taken an antibiotic is not as much an accepted belief anymore.

Victoria Maizes: Yeah, and what about FMT. In the US, we're only approving it at present for c difficile that hasn't, responded to c dif treatment but I know your lab is studying inflammatory bowel disease. So I'm imagining you're studying FMT. Tell me what you think. Are we getting closer to where we may have FMT. Available for other indications?

Suzanne Devkota: Yeaha lot of people are running clinical trials and studying this for things like Crohn's disease and ulcerative colitis largely has been studied the most in ulcerative colitis. with recurrent C diff infection, it's an easier thing to study because you're trying to just get rid of C diff. So you have a target right and an outcome that it's clearly measurable with Crohn's and colitis. These are much more heterogeneous conditions. How they manifest is different. And so the trials in inflammatory bowel diseases have not really been successful so far because of the heterogeneity and the complexity of the disease. Also, one of the issues is you with recurrent C diff infection. These are individuals who have been on antibiotics right for a long time which is why the C diff, blooms. And so they already have a sort of cleaned out system with IBD. They have an intact microbiome. It's what we might call dysbiotic or shifted towards, probably a more inflamed, adapted state. But there's a lot of organisms in there to compete with right. So if the idea is like with probiotics, if you are taking taking a

microbial preparation orally and hoping that it colonizes, if you have a lot of bugs already in there. There's not a lot of available homes to inhabit from whatever you put in there.

Suzanne Devkota: So I think the area where people have really kind of focused their attention is, what preparatory work can we do to ensure better engraftment in inflammatory bowel disease? So there have been intermittent fasting studies. So trying to create a more favorable environment through fasting. People have studied different dietary interventions to like, you know, sort of fermented food, you know sort of interventions to see if that can improve engraftment. So people have been focusing on the prehab support for these individuals, and then, after they get the FMT what sort of diet should they eat to help support that new microbiome that was introduced? And so there's been a lot of work in that in those areas. But still, you know, it's been not nearly anywhere near as successful as for recurrent C diff infection. But people are doing trials for things like metabolic diseases and obesity, and there have been some in the Netherlands studies with autologous fecal transplants, you know, banking your own, you know, stool and putting it back in or taking stool from a healthy, metabolically normal individual into a someone with with diabetes and seeing if you can manage their blood glucose levels and the data there is really compelling. But it's transient. It works for it has an effect for 6 months, and then there's a rebound. So maybe you need multiple Fmts. So people are saying all permutations. How often you need to give FMTs. What's the best way, or nasogastically or enema wise, you know, so delivery mode. So it's still a little bit of the wild west. Outside of the recurrence C diff space.

Victoria Maizes: Andy, you regularly advise people to avoid ultra processed food, and maybe you could talk about all the problems with ultra processed food.

Andrew Weil: I think it's the the rising consumption of ultra processed food is one of the factors that's driven obesity that has probably driven a whole lot of other diseases, and I would think is also responsible for significant changes in the gut microbiome in our population.

Victoria Maizes: And it has these unusual components, chemicals like flavorings and preservatives, additives, not things. You'd find in whole food.

Andrew Weil: Yeah, we and we have no idea what their effects might be.

Suzanne Devkota: Yeah there's a whole area of research in the microbiome space folks just on processed foods and food additives. And the date is probably one of the most exciting areas in the microbiome space, because the data has definitely shown and has really pinpointed certain food additives that will shift the microbiome. So there's shifting. The microbiome is one thing, and that's important. Just knowing that a specific food additive can shape the microbiome in one way or the other. But then they've been studied in inflammatory conditions, and they find in many ways the inflammation gets worse, and they can trace it back to some effect on the gut microbiome. So you know, some things that have been studied a lot are food colorants. So like, I think red 40 has been very strongly implicated. And there's actually a really interesting chemical pathway that microbes actually transform red 40 int a nasty byproduct. Things like emulsifiers have been studied a lot. Carrageenan and things like that. Yeah. So emulsifiers will promote inflammation in animal models via these certain bacteria that can that can metabolize them. Things that affect flavor like triolose. It's actually added to meats often to make them a little bit sweeter. And that's been shown to actually promote C diff growth. And so this area is booming in the microbiome space because it really is about chemical transformations. And microbes are very adept. Whether it's the drugs you take as part of your medications. Bugs don't see any. They just see chemicals, and they transform them. And so if you put chemicals in your body, you're going to get some likely somewhat, especially if you consume a lot of them. You're going to get some microbial transformation.

Victoria Maizes: One other question about medications. I think most of the listeners will know that antibiotics are going to affect the gut biome. But what about other medicines, things like anti-inflammatories, or Tylenol, or some of our biologics that we use in rheumatological conditions. How important are those either for enhancing the health or the opposite, making your health worse.

Suzanne Devkota: Yeah, this is another very hot and interesting field, and it's largely been approached through the observation of responders and non-responders to medications. And so when you think and that's that's the big mystery. In all conditions treated with drugs is you never have 100% responders. And so in some of them, you might, you know, only get 30% responders when you think about some of the biologics. And so why is that? And the micro people really been looking at the microbiome amongst many things, genetics, and so on as a potential driver of that. So when a drug company is developing a drug, they do all the kinetics right on the drug. And microbial metabolism is part of that. But a lot of that data never becomes public. And so we have to run those studies ourselves and try to understand how microbes might be interacting with different medications. But there's so many medications out there. Where do you begin? And so many of my colleagues have, taken some systematic approaches. Some have really studied statins, as there's some compelling evidence there.

And I'm in the inflammatory bowel diseases space. So there's clearly non-responders and responders to anti-TNF therapies and things like that. And so people have been studying could the microbiome be involved? And so there's definitely been papers that have shown microbial transformations of like 5 ASA, which is a, you know, old school anti-inflammatory, for IBD used far less in the United States now, but a big paper came out, showing that 5 ASA can certainly shape the microbiome in certain ways that are distinguishing of some of these responders and non-responders.

There's been really kind of interesting work in the GLP1 space and microbial production of this protease called DPP 4, which degrades GLP1 and showing that potentially, you know, microbial produced proteases can make drugs less effective. Suzanne Devkota: And so there's all of these interactions that are are compelling likely doing something. But again, it's so individual. So if you're if you don't have the group of organisms that make the protease, and you wouldn’t. Your GLP1 might be totally fine and work function, you know. Fine. But if you have it, then maybe you need a higher dose. I mean, it's it's very. It's like people being fast metabolizers, you know, people who are fast like when you go for anesthesia, for a surgery. If you're kind of a fast metabolizer. You might need a higher dose. The gut microbiome you have the microbe that's metabolizing XY, or Z then we should take into account that you might need different dosing based on the microbiome. And I think that's a really interesting area. But we're very far off from employing in any kind of clinical practice yet

This has been such a rich and fascinating conversation. I want to really thank you for taking us across the whole spectrum of the field microbiome research. And your content has made me think, yeah, we're still in our infancy in many ways in this field.

Suzanne Devkota: Very much so, but it's exciting at the same time to be in a nascent space. It means there's still so much opportunity. I think a lot of people get frustrated by the complexity of it. I view it as a wonderful puzzle to solve. As a curious mind, you want to get into the complexity of it all. I definitely think there is a there there with the microbiome. But over the next 10 years you're going to see much more sophisticated things come out on how we can shape our microbiome.

Victoria Maizes: Thank you.

Suzanne Devkota: Absolutely. Thank you.