Full episode transcript below. Beware of typos!
Nick Jikomes
Dr. Suzanne Devkota, thank you for joining me.
Suzanne Devkota 4:43
Thanks for having me.
Nick Jikomes 4:44
Can you tell everyone a little bit about who you are and what your scientific background is?
Suzanne Devkota 4:49
Sure. I am a microbiome scientist at Cedars Sinai Medical Center in Los Angeles and jointly appointed at UCLA and I am in the department of gastroenterology. And we, assistant professor and my lab focuses on how diet can affect your gut microbiome and either promote optimal health or lead to potential disease down the road. And we do some other related studies related to gut brain related to other other diseases outside the gut as well.
Nick Jikomes 5:28
So this is a topic I've covered in some ways on the podcast before, but for people who are unfamiliar with the microbiome at a very high level, what is it? And why is this in very general terms? A interesting object of study for us?
Suzanne Devkota 5:45
Yeah, so the gut microbiome, there's the technical what is the actual word mean? And then what is it you know, in our bodies, technically, the word is all of the bacteria in on our bodies, and the genes, in other words, the functions that they they possess. So people will sometimes interchangeably use the word microbiota and microbiome, but typically, they're actually two different things. And in our bodies, microbe, the microbiome are our native native bacteria. So they're not infectious diseases. They're not what you hear about on the news when you have ecoli, or salmonella, and or chicken or your lettuce. So these are bacteria that were colonized with us from birth, they've co evolved with humans since the beginning of time. And they colonize distinct niches in our body, the gut, the urogenital, tract, the skin, the mouth, the nose. Those are the defined niches where microbes live in it and provide essential functions for our health.
Nick Jikomes 6:51
So you said that these bacteria, and these microbes are with us from birth. To what extent is the microbiome of a newborn baby seeded by the mother versus microbiomes, that were sort of in that in that GI tract of the infant the entire time, it was gestating,
Suzanne Devkota 7:11
very controversial topic, probably one of the most controversial topics in our field, mainly because the placenta has always been considered sterile, you know, in the mother's placenta, and very few things compared to center into the baby. It's a protective area. But some studies in the last maybe 1010 years or so, sort of they found evidence that in newborn babies that or well in different contexts, but they found that evidence that prior to birth, that there was evidence that maybe babies were colonized in the womb. And that has been refuted in many ways pointing to contaminated reagents in the lab, basically point to contamination as saying it's not real, it was environmental books. But it still is an ongoing debate. I think people still want to know really, at what point are babies colonized the I would say the most widely accepted belief in theory, and where the evidence points to is that a baby's first exposure to bacteria period is through the mother's birth canal, right? The vaginal microbiome, which I mentioned is one of those niches that that bacteria live in our body. And and so the question is babies who are born by C section, there's evidence that their first exposure is actually a skin microbiome, you know, because they're brought out through that through that route. So depending on how their birth, they might have different microbial exposures, but it is in that process where they they are first colonized.
Nick Jikomes 8:53
So the fact that that is a controversial question, I think, perhaps speaks to the the field being relatively young, if I'm not mistaken. I think it's sort of sprouted out up at least, you know, certainly during my lifetime. So how new is this field? When did it sort of become a major buzzing area of research? And were there any, were there any major discoveries that sort of catalyzed that?
Suzanne Devkota 9:19
Yeah, you know, if you take science as a whole, it is probably the newest major discipline that has emerged in science in recent times. And so in its current form, I would say it's only about it's been 20 years old, which is very young, you know, but little pieces, you know, the building blocks of a field probably started in the, you know, 70s with Carl was at University of Illinois. And really, we point to him as sort of the one of the people who initiated this field because Prior to his research, the way we understood bacteria was through classical microbiology methods, you look under a microscope, you isolated live bacteria, you look at it under the microscope, you might stain it, look at morphology, and you've been made to it. And microbiology really didn't innovate upon that for many, many decades. And so our knowledge of the microbes on Earth and in our body was probably about 1% of all microbes, actually, that live on on Earth. And what revolutionize that was Carl was discovered that there is a unique genetic signature and bacteria that distinguish it from human cells and yeast cells and other, you know, other micro organisms. And so there's a genetic signature, it means you no longer need a live bacteria, all you have to do is isolate DNA, which if you watch all the cop shows, you know, you can isolate DNA from an old crime scene from dinosaurs, you know, you don't need the live bugs anymore. And he that that's what revolutionized the field. So now we could start looking at Whole communities, complex communities, that are mixed and contaminate with other types of DNA by simply amplifying that gene, which is called a 16. S ribosomal RNA, and you amplify it, and then you get rid of everything else. And all you're left is the bacteria, all of the bacteria that are in a given sample. So now we not only had a new way to look at bugs, but we could actually see the true diversity of life. And now at that time, they didn't have PCR, you know, so amplification was done manually and was done very, you know, non scalable. I'd say the next piece of innovation was automation, and high scale sequencing technologies. And a lot of that was brought about by the Human Genome Project, you know, human sequencing, we borrowed those tools, applied it to the microbiome, and then the whole field really exploded, it was really the sequencing revolution, that that changed, made the field what it is,
Nick Jikomes 12:05
I see. So, up until a few decades ago, it was basically impossible to tell bacteria, DNA from human DNA and other types of DNA. But once you have that hook, you can literally take a sample from inside our bodies or outside our bodies from anywhere and pull out the bacterial DNA distinctly from all the other types of DNA. But up until that point, you couldn't do that. So the material were sort of invisible in a way. Mm hmm, exactly. So one of the things that I think is most interesting to people here is how this microbiome is modulating by and interacts with what we're actually putting into our GI tract. So the food and the composition of the diets that we have. So how, how responsive is the microbiome to diet? Is it very plastic? Is it actually not that responsive? How do you start to think about that?
Suzanne Devkota 12:57
Yeah. Other than antibiotics, which is like a nuclear bomb diet is, is the one thing that can really shape your microbiome, the microbes are very, very responsive to the foods that you eat. In part, because that's what microbes are in our body, they have enzymes from breaking down food that we don't have. And so that's part of that coevolution. So in part, they have to be very responsive to foods. And there's a lot of studies showing, you know, people raised in different parts of the world have very different microbiomes and pointing largely to the types of foods that they eat. And so it's also food is also one of the most hotly studied area in terms of the microbiome, because that may be the opportunity, the non antibiotic approach to reshaping maybe what's, you know, less less than good or bio, and promoting health.
Nick Jikomes 13:55
So you mentioned antibiotics. So I'm interested in all of the different ways that you can change the composition of the microbiome. So I think it's worth talking about antibiotics themselves, just given that, obviously, they're going to kill the bacteria in your body, including the microbiome, but specifically, because they're so widely used these days. So I'm wondering if you could comment on that. And then, you know, I think an adjacent topic there is the topic of probiotics and prebiotics. So can you start to tease that apart for us?
Suzanne Devkota 14:26
Yeah. I mean, a lot of thoughts on antibiotics. they've sort of been a blessing and a curse. And in many ways, obviously, without antibiotics, we would not have the lifespan in many ways that we have today. But there's also been an overuse of antibiotics. And interestingly, it's there's a, it kind of varies regionally. So certain parts of the country are very heavily the medical institution very heavily prescribes antibiotics and other parts of the country. They're very selective. And I think that's an interesting thing to think about. But the reality is there have been no new antibiotics really invent created in my current in my current memory, so what we have today is what we have. And our last defense antibiotic that we will consider is called vancomycin. And mega myosin is one of the most commonly used antibiotics in agriculture and livestock. And so we're just using it kind of willy nilly in other in other industries. And I think there's a risk there because we can inadvertently create resistance to our last line of defense, which is this particular antibiotic. Why are there not any new antibiotics and part there isn't good funding, people don't typically fund antibiotic research. So there's probably more systemic issue there. But maybe I think our minds are thinking a lot more about infectious diseases these days with COVID. So I think that might change I hope, I think bacteria are far more dangerous and viruses are because they don't actually need a host to survive, whereas viruses do. So I think we have to really be thinking about the future, because I don't think this is our last pandemic. So So antibiotics, you know, on a more personal level, you know, day to day, chronic use does create antibiotic resistance, there's no question about that. And so that is a concern in terms of the microbiome. Antibiotics, like no one antibiotic gets rid of all of the bacteria, okay? They tend to target specific features on certain types of bacteria. So often in the hospital, a combination a cocktail will be given. And it may get rid of an infectious disease, but the collateral damages, you also get rid of your good bugs, your your gut microbiome bugs, and that's where a lot of the research has focused is that collateral damage? What does it mean? Like? How are you recolonized once you take an antibiotic, and I think there's so there's been some really interesting data where they've taken people with different people who've been on repeated antibiotics, and they follow the colonization of recolonization of the gut microbiome. And they find that some people will be recolonized, just like they were before. But it takes three to six months to get to your back to your starting point. But other people will recolonize to a new normal, a different profile, and they're otherwise healthy, but it's just different than it was before. And those people are really interesting, what is it about their biology, their exposures, that caused their microbiome when it's wiped out to just be something totally new. And there's some evidence that that may lead to other diseases, inflammation, autoimmunity, things like that. So that's an interesting area to study. People talk about probiotics, you know, in terms of recolonizing, the gut after antibiotics, I used to be one of these people that prescribed you know, nuts, prescribed because they're over the counter, but recommended antibiotics after I mean, recommended probiotics after a course of antibiotics to speed up that recovery. Now, we know that actually may not work and can actually cause worse problems. So there is actually some research showing that taking a probiotic after antibiotics can actually delay the natural recolonization of your gut. And so that is an interesting concept. You know, it's a little counterintuitive, but there's evidence to show that that is true. So people don't really recommend that anymore.
Nick Jikomes 18:30
So it's the idea there. If you're on an antibiotic for an extended period, especially, you're basically carpet bombing your body, you're clearing out many of the bacteria that are going to be in your gut. The the natural recolonization process would involve bacteria growing in response to the diet, that you're having the nutrients in the calories that you're putting through your gut. But if you take a probiotic, would the way to think about the speed that the bacteria coming from the probiotic are basically taking up space and out competing some of the other bacteria that would come from the natural recolonization.
Suzanne Devkota 19:06
Yeah, I think that's part of it. I think that you know, because if you look at probiotics that are on the market, there near a pretty narrow spectrum of bacteria, there might be at most five different organisms in a pill. But we have in our gut 500 to 1000 different types of species. But if you just flood the system with these five organisms, they may actually take take hold and while they're good bugs, you everything has to be balanced, if you have an over balance over colonization of these bugs, that could also cause problems. So that yes, this this available niche occupying the available niches as part of the issue.
Nick Jikomes 19:51
So antibiotics are very common. You can get them from the doctor, you mentioned something interesting, which is there are regional differences in the rates that antibiotics are prescribed. Have you also mentioned that antibiotics are just on or in our food? Right? They they're used for livestock purposes. They're used for other purposes. So even if you're trying to avoid antibiotics, you're probably not avoiding antibiotics. related to that topic. I assume this has been done experimentally, I'm pretty sure it has been. What happens if you just constantly give an experimental animal, say antibiotics to minimize is basically just take out as microbiome as much as possible for as long as possible? What are the major health consequences of not having your gut colonized by anything?
Suzanne Devkota 20:38
So has a good question. Has someone like what is the I try to think of what's the longest term I've seen in a study of antibiotic use? I have to actually think about that. But if you if you think about, you know, going back to the concept of coevolution, and these bacteria co evolved with us to provide essential functions that we don't have in part, you know, because of that coevolution, we have lost the ability to metabolize certain foods on our own. So to get rid of our bugs and certain foods won't be fully metabolized, you know, we won't extract all of the vitamins and minerals from that food, that's one thing. The other thing is there are certain B vitamins, for example, that only the bacteria produce, and that we absorb. So you can create a further, like vitamin deficiency, if you totally get rid of your, your microbiome, so a lot of benefit to keeping them. You know, there's been some studies where they've shown like, Okay, if bacteria might promote obesity, then if you get rid of them, then are you skinnier, you know, there's been like in animal models, some studies where it shows Hey, maybe getting rid of bugs is a good thing. But there's also been the opposite study showing they're in the same context, they're also detrimental. So we definitely want our bacteria. The only, you know, kind of interesting example is we have these mice called germ free mice that we use in research. And these are mice raised from birth without any bacteria in their body at all. And these, these mice, they're very happy, they're very healthy, they have a lot of babies, you know, when they when they give birth, more than the conventional mice, but they live in a completely sterile bubble. So they're in this happy universe where there are no bugs don't exist at all. As soon as you take them and put them into our world, a lot of them will just die, because they cannot handle the immunological onslaught that happens with being exposed to our world, all the engines that that they see. So if we weren't able to live in a completely sterile world, then we could live in to some degree without bugs, but because we don't we need our bugs and third form of defense in many ways. So are
Nick Jikomes 22:53
they are they literally can one role that the microbiome is playing be thought of almost as a literal shield, where just the fact that they're occupying that space inside of us is preventing other potential pathogens from occupying the same space?
Suzanne Devkota 23:10
Yeah, we actually are doing a study right now on COVID. Asking that exact question. So there is there is has been a finding very early in the pandemic that when patients you know when you are positive for for SARS, cov, two in the sputum or in the lungs, even after you clear the infection and you have negative tests, you can still be positive in the stool. So the virus lives in the GI tract as well. It's not just upper respiratory. And it can persist for weeks, even after you have negative tests. So there's something about you know, and in the in the reason is because there's the receptor, the h2 receptor that it binds to in the lungs, its biggest density is actually in the GI tract. So the virus is there. But why does it persist? Well, we were we were curious about this question. And so we wrote a grant and started a study. We're collecting fecal samples from inpatients in the hospital COVID in patients. And one of the things we found associated with the persistence in the GI tract was antibiotic use. And so the patients when they come into the hospital tend to be put on a lot of antibiotics to prevent secondary respiratory infections, like you don't want to have COVID and pneumonia or you know, another issue. So they get put on broad spectrum antibiotics, which wipes out their gut microbiome as well. So by eliminating that barrier, is it providing a much more open clean slate for SARS cov to to come in and bind to all of its receptors and persist. And so we do see an association with that persistence and the use of antibiotics in the hospital. So I think to your point, yeah, I think bacteria do provide a barrier that prevents against colonization. This has been shown in other viruses and Zika virus with dengue virus, West Nile virus, they have found that these have been in animal models when they give antibiotics and then infect mice with these viruses, the virus persists in the body much longer.
Nick Jikomes 25:11
I mean, this makes a lot of sense to me, because we're so distant from bacteria that generally speaking, right, the same virus that can infect a human cells, almost certainly not going to be able to infect a bacterial cell. So if those physical bacterial cells just aren't there, you've now exposed all of these receptors and things that a virus that can infect us can now touch and get a hold of. Is there any evidence yet that in such individuals where you have SARS cov, two persisting in the GI tract, that there are any GI issues being caused by the virus?
Suzanne Devkota 25:48
Yeah, that was one of the biggest early symptoms of COVID was Gi, you know, whether it was pain or diarrhea. But they're definitely gi manifestations was sort of the blanket term was was one of the emerging signs in the early pandemic, you don't see it as much with these variants now. But yeah, and that's what really got us looking there in the first place was because these gi manifestations seem to really be increasing. So I Yes, I think it that is part of the persistence in the GI tract is why we are seeing these GI issues.
Nick Jikomes 26:25
Interesting. So one, well, I think we'll come back to this actually, people are taking a lot of precautions in their life, due to COVID just being cleaner, and more hygiene conscious generally. And I want to loop back to that. But another topic here that I think is interesting is that, presumably, the composition of the microbiome is not homogenous, as you go from one end of the of the digestive tract to the other. There are different environments and your mouth and your esophagus and your upper versus lower GI tract. How much does the composition of that microbiome change there? And what are some of the interesting differences that that you see?
Suzanne Devkota 27:07
Yeah, this is a fairly, I would say, I was gonna say fairly well studied. But it actually isn't, and I'll get back to you. But generally, you go from decreasing density and diversity in your upper GI tract, so meaning the esophagus and stomach and as you go distally towards you know, your anus, it gets more and more dense and diverse. And part of the reason is that bacteria, I mean, you can think about it like a wastewater pool, or a standing pool of water, things molten when they're stasis, when there's still stillness, you get a lot of multiplication, in the parts, your GI tract where there's a lot of flow, right, your esophagus, your stomach, your upper GI tract, you don't have a lot of colonization, because there's constant movement. So your colon, which is generally sort of the last stop, right, where everything is just sort of a holding place and your your, your fecal matter is getting concentrated water is being reabsorbed to the body. That's where you have the highest density of bacteria and where most of your fermentation occurs, and then your colon. And so, you know, this is part of an issue, why, you know, chronic constipation, actually, there's a lot of risk factors around that. Because if you have, you can't keep that flow going, then bacteria can multiply and overgrow into places where they shouldn't be and that can cause problems.
Nick Jikomes 28:33
Interesting. So on the so you mentioned earlier that, you know, one of the things that many of these microbes do is digest foods that we no longer can digest, we've we've lost that bit ability over time. Because we come into relationship with some of these bugs. What are some of the the salient examples of nutrients, either macro or micro nutrients that are important for nutrition that are entirely dependent on the microbiome to actually get?
Suzanne Devkota 29:02
So the Hallmark example is fiber. And fiber is actually there's, you know, fiber isn't just one thing, there's many different kinds of fiber, you hear about soluble and insoluble and fermentable or non fermentable. If we use the classification fermentable and non fermentable, that refers to what the microbes can do with the fiber you eat. And so there are certain like soluble fibers that our body will, we will eat and we can sort of break down and use and that that's something our bodies can do. But there's there are several types of fiber, where only our bacteria will break it down. And one of the things that they do with that fiber is they'll use these metabolites called short chain fatty acids, and short chain fatty acids are absorbed by the intestinal cells, and they use them for energy and it actually promotes like a healthy gut. barrier and promotes a good mucous layer and so protects that barrier in your, in your gut. So that's why, you know, if you ask any microbiome scientists what they eat, they're always going to tell you fiber, because fiber feeds the gut bacteria, it's called a prebiotic, and promotes ultimately, it's not just so you can have a happy microbiome so that you can promote the organisms that were produced the short chain fatty acids for our gut health, but people are studying I mean, we study other people study, like what else beyond fiber can be can be beneficial that the bugs might might use and so it's still early days in this in this area. I think, you know, there is a lot more than just fiber that the bacteria can metabolizing and produce beneficial byproducts. But that's the thing we always point to, there's a lot of research into, you know, like fermented foods right now. Because that's, that's a situation where there's a food that after the fermentation process that I'm talking about in the gut is actually happening to being in a jar or a bottle of kombucha, right. And you can actually take that product and drink it or eat it, and still get that beneficial short chain fatty acids through eating a product that has it. So it's you can either coax it to happen in your GI tract, or you can consume it. It's it's kind of interesting, but fermented foods are like, awesome,
Nick Jikomes 31:24
interesting. So what about, so it makes a lot of sense that we would get nutrients from some of these bugs? That's part of the reason that some of them are there. Are there any other interesting areas of study that involve, say, the production of metabolites by some of these organisms that do other things? So not necessarily, necessarily like vitamins and food nutrients? But are these microbes producing any other molecules that can get into the bloodstream and travel elsewhere in the body to have some kind of effect? In particular, since my background is neuroscience? are they producing anything? They can actually get all the way up to the brain and have effects inside of the brain say?
Suzanne Devkota 32:05
Yeah, absolutely. I mean, that's the hot area of research. The research direction in that area is often on the pathogenesis side. So disease causing microbes are really good for us. But they can also cause problems, if they're, you know, maybe have an imbalance of microbes, you have an overgrowth of potentially harmful bacteria. So, so the x was a couple examples. One is there's a really interesting area of research in the cardiovascular field where consumption of dietary choline, which can be sometimes in fish, and sometimes in meats and cheeses, the bacteria can convert choline into something called trimethylamine. TMA, which TMA then travels into the blood to the liver, and the liver converts it to TMA, oh trimethylamine oxide. And that production then has been shown pretty robustly to lead to atherosclerosis. And there's been some human studies where they show people who have atherosclerosis have a high blood level of this TMA, oh, and they traced it back to these these microbes. So that's a that's kind of very interesting example of sort of the spy product being converted and then cosmic issues. In sort of a gut brain world, we actually are we ourselves are doing a study right now in Parkinson's, where we're looking at how metabolites in part short chain fatty acids are one of them can actually, they actually can get into the bloodstream. And they've been shown to be able to pass the blood brain barrier and affect different behavioral things and also potentially neuronal degeneration and regeneration. One of the more interesting studies I had seen was a one of the short chain fatty acids propionate has been shown to have like satiety inducing signals, so it makes you feel more full. And they traced it back to bacterial production, triggering these satiety signals in the brain. So one of the thoughts was, what if we just eat propriate? Nate, can it be like a weight loss, you know, weight loss drug that hasn't really panned out? I think it's more complicated than that. But these these volatile gases that the microbes make, definitely can get into the bloodstream and affect distant sites. And the brain connection is a very hot field right now.
Nick Jikomes 34:34
Interesting. So I know that in certain infectious disease states, you get an infection in one part of your body and if it gets particularly bad, or there's some kind of rupture or something, bacteria, you know, that are causing problems and one organ can get into the blood move, physically move somewhere else, and that can cause problems because they just wreak havoc in another place. Does that ever happen? Do gut bacteria We ever somehow get into the wrong place or get into the bloodstream and get somewhere they're not supposed to be.
Suzanne Devkota 35:06
Yeah, this is also another area we're interested in, in the classical sense, you know, in infectious diseases, we think of sepsis, that's the classical situation of bacteria, harmful bacteria leaking into the bloodstream and causing massive inflammation and infection. This doesn't, with your native bacteria, you don't tend to get sepsis in that same in that same way. But that Tyria have been recovered from unusual parts of the body, that have not been the result of contamination. And so some areas where bacteria appear to be traveling to, in our research, we're studying bacteria in the gut, that actually, when there's chronic intestinal inflammation, like disease, bacteria can actually leave the gut and embed themselves in the fat tissue that surrounds the gut, the mesenteric fat tissue. And when they do that certain species, when they actually go into the fat, they communicate with that environment, the fat cell environment, and actually can cause inflammation in the fat and cause the fat to grow. And so we're now studying this in the context of obesity, which is sort of the watch next next step in that study. But people have discovered native bacteria in the bladder, the bladder is typically considered a sterile, sterile organ. But there appeared appear to be bacteria there that don't necessarily are not related to like a UTI. And then I mentioned you know, the placenta, you know, there are there bacteria there or not, all of those contexts that I described are what are called like translocation events, bacteria that are from another area, leave travel, take advantage of some weakness in a barrier and go somewhere. The interesting thing is, when a bacteria leaves its native environment, it typically he can't survive in the new place, right? So the bacteria, you tend to find in these new places have some evolutionary adaptation that has given them, you know, a competitive advantage to survive there. And those isms are interesting to study.
Nick Jikomes 37:24
Interesting. So getting back to the topic of whether any of these bacteria or communities of bacteria have a causal role to play in any disease states, has anything clearly been identified, there were the culprit is really the microbiome itself.
Suzanne Devkota 37:45
Yeah, that's the Holy Grail, you know, to find, find, you know, a bug. The reality is, it's likely never going to be one organism that causes a disease. It's usually a community, a particular community profile, or a group of related organisms. Now there's there is a type of inflammatory of colitis, called Clostridium difficile colitis. And this is a organism that is considered a pathogen, but actually it kind of exists as part of our native microbiome as well. You might hear a bit of C Diff colitis. But C diff, can in many cases be eradicated by antibiotics that causes massive inflammation. But when it recurs, in you get recurrent classroom difficile infection, one of the most potent treatments for that is a fecal transplant. And it's exactly what what it sounds like is taking healthy poop and colonizing a patient that has C diff. And that it that will be eradicated push out basically that that Clostridium difficile infection, but that's an example of a type of colitis where a single organism is causing that that manifestation, but there are a few that I can point to that are native gut bugs causing one disease.
Nick Jikomes 39:21
And so what other sort of gut or metabolic issues generally, do we are we studying right now that have something to do with the microbiome even it's not the causal agent, that it's it's modulating, say, the severity of what's wrong?
Suzanne Devkota 39:39
You name it. Right now. I mean, people are applying every for better or worse, applying the microbiome to almost every disease. I think it's important to keep an open mind. But I think in the end, there's going to be a very narrow spectrum of diseases where the microbiome is actually the true culprit. I think in almost all diseases, the microbiome is the factor. But it may be secondary tertiary factor, not a direct, direct relationship. For you know, I think the biggest candidates, certainly anything related to gastrointestinal inflammation. So all the inflammatory bowel disease conditions, Crohn's Colitis, that's already been proven to have a microbiome relationship. The other areas that people say next would be like liver, liver diseases, because that's sort of attached to the GI tract. So you, you will sometimes see bacteria translocate there, and there's evidence of bacterial effects on on fatty liver, things like that. The area that surprises me the most that it seems there should be a very obvious relationship, but there hasn't really been sort of a key connection made yet his metabolic diseases, diabetes, you know, cardio metabolic diseases, especially as we talk about diet, you know, bugs are so involved in helping us break down foods and promoting our optimal health, shouldn't there be a connection with metabolic diseases in some way. And there's been some compelling data and papers and research that is, has come out and is ongoing, but it hasn't been as robust as the immunological diseases. And I'm very interested in that space in the metabolism space, but we need more people in it setting it.
Nick Jikomes 41:32
What about something like obesity? You know, at this point, I don't even need to mention the specifics. But, you know, it's been such an issue for so long. You've got now I think over 35% of US adults, as of a few years ago. So it's probably even worse now that are classified as obese. Is there any connection here with the microbiome? And, you know, especially any connection with potentially altering the microbiome to to decrease obesity levels?
Suzanne Devkota 42:01
Yeah. You know, some of the very earliest work that came out in the microbiome field was in obesity, sort of the proof of concept studies that showed the microbiome could transfer phenotypes from lean to obese or obese to lean, I guess it's actually. So that was the first place people went and then the field opened way up. And we diversified a lot more in terms of what we're studying.
Nick Jikomes 42:29
Before you go on, Can you unpack that a little bit? So people took mice that were obese, basically took out their microbiome, put it into a lean mouse, or vice versa? And so what exactly happened?
Suzanne Devkota 42:41
That mice became fat? Basically, that's the exact experiment. Yeah. They found that mice would eat more and gained weight more by take it by having that obese microbiome, then they also look at twins, you know, twin studies that were discordant for obesity, so obese twin and a lean twin to remove the issue of genetics, right. And they found that the obese twins would have a different microbiome than their lean. Miss brothers sister, identical twins actually sister, brother. And so then it was but all of these were association studies, in many ways, you know, like a certain Metria profile is associated with obesity in the human setting, at least Yeah.
Nick Jikomes 43:23
Is there is a difference caused by the different eating pattern? Exactly. Reverse? Yeah,
Suzanne Devkota 43:29
yes, cause an effect chicken or the egg is the biggest issue we struggle with in the microbiome field. Because it's so plastic, responds to a lot of things. But those were the early obesity studies was was that and they pointed to in the mouse studies, at least they pointed to this bacterial profile being mated to a certain fatty acid binding protein. And so there is the debt identified some molecule but also, the the sort of hypothesis they gave was that the obese microbiome is more efficient at harvesting energy from food. So the analogy is if you gave two people a, the same Big Mac, and let's say that big math is 800 calories, the person with the obese microbiome would extract 800 calories from that the person with the Lean microbiome might actually extract 600 calories, you know, if you count for heat and all that sort of stuff. So the obese microbiome is just more efficient at harvesting calories from any given food than the link counterpart. And they pointed to actually certain bacteria now in different hands, that has been proven and disproven and not been consistent, but it still is a is a thought that that prevails. And part of the reason is because what we do know is gut microbes. So if we are basal energy metabolism is let's say I need 1500 calories to maintain my weight. have that 1500 calories per day, my gut microbiome might actually be providing 20% of that calorie just through recycling through that fiber fermentation and all of that. So gut microbes actually produce molecules that are converted to calories in our body. That is a real process that happens. So is that more efficient in an obese person? That was the early questions being asked?
Nick Jikomes 45:25
Has anyone ever done the the natural study that perhaps you might do where you have a range of obesity levels in a population of people that are taking antibiotics for some other reason for an extended period of time? And observed whether or not there are any, any changes there?
Suzanne Devkota 45:46
Good question. I can't think of any off the top of my head that have done that. But what what some very kind of famous studies that have been done, somewhat related were fecal transplant studies and diabetics and non diabetics, and who, some were obese and some the non diabetic or lean. And they found that taking the Lean non diabetic gut microbiome and doing a fecal transplant into a diabetic for a short period, I think, three to six months, actually reduced their basal, you know, blood glucose and HBA once see. Now it rebounded, probably because that microbiome was either store, or I'm not sure why. But for a short period, that phenotype was actually the non diabetic phenotype could be transferred to to the host. And that data has been pointed to as a really robust example of the power of the microbiome. But But fixing these changes, long term like has been has been the issue that's much harder to do.
Nick Jikomes 46:53
So on the top, so it sort of related to the topic that we were discussing earlier of antibiotics, so things that will disrupt or destroy at least parts of your microbiome. You know, over time, I think it's quite clear that the general trend for humans living living in the modern world is, you know, more use of antibiotics and antivirals, more cleanliness and hygiene centric behavior. You know, you can imagine, and, you know, I've, we've probably all seen firsthand that during this pandemic, you know, people are changing their habits. Sometimes it's in direct connection with reducing the chance of infection. And sometimes it's, what would you call it, it's extraneous behavior that's probably perceived to prevent an infection. But in fact, it's probably not having an effect. And everything from just, you know, washing your hands more or obsessively to completely sterilizing every part of your house every time you can, to, you know, not letting children play in the dirt and get and get literally dirty. How much of our hygienic behavior has ramifications for our microbiome, generally speaking, not just the gut microbiome.
Suzanne Devkota 48:06
I think about this a lot. Especially in the current current, you know, what we're going through right now in the pandemic. There's so many facets to this, this question. First, I'll backtrack. And when I when I give talks, I tend to show this figure of New England Journal, medicine old old figure, but it's really powerful. And it showed sort of disease incidents over time starting the 1900s, to modern day. And what it showed was that starting in 1900s, through about 1950, there was a massive decrease in acute infectious diseases, owing largely to vaccines, antibiotics and hygiene. And but then what began to increase with chronic diseases that we might call New Age disease. So food allergies, autoimmune diseases, IBD, obesity, diabetes, all of those increased as the other as hygiene kind of increased. So that sort of the, the concept of the hygiene hypothesis then came about saying, Okay, there's a, there's a, there's a, it's like a bell curve of hygiene, right, there's a point where you need to be high, you know, hygenic, so that you don't die from acute infections. But then there's a point where it's too much, and you actually start causing collateral damage. And that too much hygiene, actually, you stop educating your immune system in the proper way. And then you get autoimmune diseases. And so, that's one of the reasons why, you know, there's been some more some books published from from colleagues of mine about, like books called, you know, let them eat dirt about kids and how you should like kids play in the dirt and I think prior to the pandemic, I think people were really appreciating that, hey, we need to expose our kids to more pets, you know, Pets and play outside and it's okay if they get into stuff, then the pandemic hits, and it was all, you know, that was all off the table. And we had to wash our hands a certain amount of time and certain way and it was just we need to eradicate. So I think about what's going to be the long term effect of that. Now, in terms of all of this hygiene we're doing right now. Now, there's a purpose to it. And I think it's important that we shouldn't stop washing our hands and maintaining a distance. But there's, you know, we walk around with what's called, like, a microbial cloud around us. It's not just inside us, you know, we have, you know, microbes all around us. And we have microbes very similar to people we cohabitate with, because we exchange microbes. So with lack of socialization in the way that we used to social distancing, you know, we're not commingling our microbes as much anymore. What does that all mean? I don't know. I don't know. I'm very curious as to what this next five years is going to hold? You know, to see if we will see some something, you know, will it exacerbate the existing chronic diseases? Will something new, you know, emerge? I don't know. But I think it'll be very interesting.
Nick Jikomes 51:15
So some questions that are coming to mind that I want to ask you about, I don't know if you'll have answers to these. But I think they're really interesting to think about. So I'll take a minute to just unpack some concepts for listeners here. But we're gonna think about the microbiome in parallel with the way that we think about the immune system and its diversity from an evolutionary perspective. Now, from an evolutionary perspective, what has happened in our lineage, and in many lineages is that diversity in the population for immune system traits is itself what's selected for. So natural selection seems to favor populations that have a very quite high diversity in terms of their immunological repertoire. So when you look at the genomes of people, and you look at their immune systems, you tend to see that they differ quite a lot. And in fact, when you look at the mating habits of people and other critters, there tends to be a sort of mating. Along this dimension, people tend to basically be attracted to various aspects of people that indicate that the other person has a very distinct immune system from them. And the the idea there is that two people with very similar immune systems are going to produce a different kind of offspring than two people with distinct immune systems. If you have two people with distinct immune systems, the immune repertoire of their offspring will tend to be more diverse and able to handle more things. That's the basic idea. I'm wondering if there are any analogies there with microbiome stuff? Do people you know, when you think about things like cohabitating, with someone eating the same food? When you think about various romantic gestures and physical interactions people have? You're essentially, I would think sampling someone's microbiome? And is there anything interesting going on there where people tend to want to associate with someone that has a distinct microbiome or anything like that?
Suzanne Devkota 53:13
Yeah, the social questions is very interesting. Um, you know, one point I want to make since you started off the conversation about, you know, analogies to evolution. If you're trying to understand the microbiome, when all you apply evolutionary biology principles to to the gut microbiome, all of those principles are the same language we use, you know, fitness, competitive advantages, things like that. So it is Darwinian evolution, at its finest in the micro scale that happens very fast, is what you know, that our gut, actually our skin, you know, just these microbial communities on our body are so if you ever want to, you know, on your own answer a question, just think about what, what in the wild would happen, you know, if, if, if now just apply it to your microbes, in terms of you know, does does the need for diversity, diversity, the concept of diversity is one of the central metrics we use in microbiome research, like analysis to define health, or disease, the more diverse your microbiome is, the more healthy you are, and if you lose diversity is typically associated with disease. So So why is that a you know, obviously, again, evolutionary biology makes sense. But there's a lot of what we call functional redundancy in our gut microbiome. So you can have a lot of different types names of bacteria, but many of them may do the same thing. And the reason for that is if you take an antibiotic, and it wipes out some of the bugs that are carrying out an essential function, you need other bugs that can still carry out that function for you. So there's a lot of functional redundancy in the gut microbiome and that's evolutionarily To create a fitter microbiome and a fitter host. So, so that's an important principle to just kind of put out there. And so when you have low diversity, you're obviously going to be losing some of that redundancy, and it puts you at risk for, you know, not being able to carry out in the central function. On the on the social side, you know, there's very little, you know, there's very little work on do does our microbiome sort of need to be diverse Dr, how we behave in this world. But one study I do I do talk about in my talk, sometimes I think is very interesting is this one, where they looked at married couples and unmarried couples, and within the married couples, they stratified them between ones that define themselves as very close having intimate relationships and ones that that were not, as you know, described himself as as close. And they found that marry couples compared to you know, friends and non cohabitating, people had much more similar microbiome. And then within that the ones that described themselves as as close had very similar microbiome compared to, to those who are not as you know, had as much physical interaction. Now, that's just sort of, you could say, Okay, it's a byproduct of, of, you know, the chicken or the egg thing you're close to, ergo, you, you commingle more, but is it that it's driving some behaviors, I don't, I don't really know, this is an observational study wasn't a lot of mechanism. But it was a really cool kind of proof, I use it to highlight that, you know, we we share our microbes with the people around us. And the closer you are to a person, it could be a mother and a baby, you know, similar thing, the more you will share your microbes. So if you're unwell and your partner's very healthy, maybe you want to be a little closer to that person, it tends to it doesn't tend to go that the disease, the healthy microbiome is not it doesn't tend to be transmitted tends to be that the more diverse robust microbiome, it's like osmosis goes from, you know, the higher density to the lower density, so you get an equilibrium.
Nick Jikomes 57:10
What do we know about the outer surface of the body and the microbiome there? I know that there's, I mean, there's obviously going to be a lot of bacteria on the surface of the skin, it's probably going to vary from one part of your body to the other. But are there any disease states associated with that external microbiome composition or any other aspects of health that we know about there?
Suzanne Devkota 57:33
Yeah, um, you know, the, the, there's far less research in skin microbiome, and gut microbiome. Because there's a lot less bugs there, it's a little simpler system. It tends to be all aerobic bacteria, because the skins exposed to the air. And so the diversity there does tends to be less. But there is an increasing amount of research in the skin space and part in industry, you know, cosmetics and lotions, and things like that. But also, many autoimmune diseases or chronic diseases, like what I know best Crohn's disease, or colitis tends to have often will have skin manifestations, skin lesions will often appear. And sometimes they're pretty bad. And no one really knows why that is. But you know, there's a gut skin axis, which is, I think, a very real thing. So there's some communication there. And people are starting to explore whether the microbiome might actually be you know, the skin microbe, or even the gut microbe might be somehow either producing a byproduct in the gut that's traveling through the blood and just finding its way to the skin and causing inflammation. Or it could be your skin microbiome is just one that when you have an immunological sort of susceptibility, it sort of takes over and causes these lesions, but no one really knows. But there are some interesting connections there. One thing that I think is important to know that this relates back to our concept of the hygiene hypothesis is our skin like our gut has a barrier. We don't we don't see it's not mucousy you know, it's it's dry, but it has a certain pH. And it tends to be a little more acidic. And it's called the acid mantle. And so every time we wash our hands, or we wash our face with soap and detergent, we wash it off, right? And we aren't often recolonizing it again. And so there's some research, you know, saying that this constant washing of the skin, certainly in the face area might be part of the reason why you have chronic acne and things like that, because you don't have the barrier, certain bacteria takeover, and they don't have competition.
Nick Jikomes 59:47
Okay, hold on, because I know so many people in my life that I'm thinking about right now. Are you saying that it's possible or even plausible, that washing your face too much? could actually contribute to some of these skin issues?
Suzanne Devkota 1:00:03
Yes, absolutely. We've gotten into the mode that we do, if we have a skin issue at the clean, clean, clean, you know, but that could actually be creating this vicious cycle. Not that you shouldn't clean, but you need to clean with the right products, ones that are not stripping ones that actually can restore, maintain the pH of your face, that clean, you know, remove oil, you want to remove oil, but you also want to maintain the barrier. So you need the right kind of products, we tend to associate that tight feeling, you know, when we wash our face as being like, you know, that's good. But actually, that's the stripping of your acid mantle. And so, there's been a lot of innovation in the space, people you might see you go to Sephora, and there's a lot of products right now that are, you know, microbiome based products.
Nick Jikomes 1:00:56
Are there any. So I am definitely not a skin product person really. But you mentioned you want the right products and you want to maintain this this natural acidic barrier. Are there any, like key principles there that you could point people to in terms of what the ingredients should be that you want in a skin product versus those that you want to avoid?
Suzanne Devkota 1:01:20
Yeah, um, you know, things like oil based cleansers, which again, is counterintuitive, but oil actually removes dirt extremely effectively from your face. And it doesn't, because it's sort of lipids are neutral, they don't mess with your acid balance on your face. So you there's a lot of these cleansing balms or oil based cleansers out there, those are good. So those are the types of things you might want to look for. And then, you know, if you say, Okay, well, I really like using this harsh cleanser on my face, because it just feels good. Totally your prerogative but then you might want to put a serum on your face that will leave on that will restore sort of the pH of your of your skin microbiome, that that acid barrier. So there are different ways to do it. But I would say you know, look for oil based cleansers to start try to wean off of the high, you know, stringent type of things. And if this is a problem for you, acne, chronic acne white, you know, it's counterintuitive, but it might work for you.
Nick Jikomes 1:02:23
And what is what, what actually is acne is that due to bacteria to sort of locally colonizing the pores and things?
Suzanne Devkota 1:02:31
Yeah, there's actually a bacteria called propionibacterium acnes. And it's a skin microbe that it's interesting that's been pointed to as a culprit for acne. That's how acne got its name. Except, like with microbes in the gut. You know, bacteria, even within a bacterial species has strains, different strains, different types of itself. And some p acnes. bugs can be beneficial, and part of your normal microbiome of the skin and you need it there and others can be the ones that cause problems. It's really about your community. You know, it's no, like I said, it's never one just one bug. It's that whole community that it's a part of. So to answer your question, yes, it's kind of one bug that's sort of been playing to driver. But as we know more about the microbiome, I think we realize it's the total community and the environment of the face that actually drives, you know, drives up the, the problem.
Nick Jikomes 1:03:29
I see. So getting back to diet stuff, one of the things I did want to circle back to, for a couple of reasons was a composition of diet, but also probiotics and prebiotics. And the reason for that is, as I'm sure you know, right, these products are like all over the place now. And it's very difficult for even an educated person on this general subject to make sense of, you know, what's good, what's not good? What's it actually going to do? Are the colony forming units at the right level, etc, etc. So let's start with diet, and then circle back to some of the things that you said about probiotics earlier. But starting with diet, generally speaking, you know, there's lots of diversity, everyone's different, but are there general principles for what is and is not going to generally facilitate a healthy microbiome in terms of the caloric density or the nutritional content of the food that you eat?
Suzanne Devkota 1:04:27
Yeah, it's less about let me take that back. Um, the number one principle is if you want diversity in your microbiome, you have to eat a diverse diet. So these very narrow like narrow dyes, like the carnivore diet, for example, is when I octuple point fixes like people like him who only who only eat meat. metabolically, there could be some benefits if you're trying to lose weight, okay. But if you only eat one type of food, you will only harbor and promote one type of bacteria, the bacteria that metabolize that food, again, its evolutionary biology. You feed the microbiome, the ones that use it will live, the ones that can't survive on that thing you give it will die off. So the more diverse foods you feed your microbiome with the more diverse microbes you'll support in your gut. So number one principle, I always tell people, please eat a diverse diet, eat a diverse diet, you definitely don't need vitamins, you don't need a multiple multivitamin or anything. If you eat from all the food groups, you will be nutrient balanced and your gut microbiome will be healthy. So that's sort of number one. And then I you know, I talked to him about fiber. That's an obvious one. You know, I don't need to belabor that point. But just a general guideline for people, you want to be eating at least 20 grams per day, most people barely get 10. So we all need to eat a lot more fiber. So look at that label, when you eat something you think is high fiber and make sure to actually use high fiber. And then fermented foods I talked I touched on as well, highly recommended that will support a healthy gut microbiome that will support diversity in a very major way. There is a study I can point to that came out recently, where they took help otherwise healthy, young, healthy people, and instructed them to increase their consumption over a period of few weeks of either fiber rich foods or fermented foods. And they looked at inflammatory markers in the blood. And what they found was individuals that were on the increased fermented food diet had a reduction, every single inflammatory marker in the blood at the end of the study, more so than in the fiber rich group.
Nick Jikomes 1:06:53
And their time what some of those key fermented foods are.
Suzanne Devkota 1:06:57
Yeah, so some examples that that are commonly consumed would be kombucha, which is my personal favorite. So and there's other like vegetable, brine drinks you can buy at the store. So fermented beverages, not necessarily beer and wine, but sort of a more raw type product, kimchi, sauerkraut, some pickles, not all pickles. They're even like fermented hot sauces out there. Anything that is fermented, is that you will see on the label, you know, it has to sit in a jar for a while before you eat, it is usually going to be good for you.
Nick Jikomes 1:07:38
So probiotics? Yeah, you know, I've heard mixed signals on this. And earlier, you said that generally, that's not being recommended as much anymore. So what's what's the current state of state of knowledge with whether or not you should be taking any probiotics? And if there are any what what are the ones that one would take?
Suzanne Devkota 1:08:02
So that that is still somewhat controversial, or I don't maybe not controversial, you still get you still get conflicting recommendations from people. I think a lot of physicians still recommend probiotics. on the science side, those of us doing the research generally will say don't take probiotics. Then you have people who have empirical evidence like themselves, I was feeling bad take a probiotic, I feel better. In those instances, I say keep doing it. If something doesn't, I don't think all probiotics don't work. I think there's there's there probably contexts where they are helping someone. But it's really there's no blanket statement where I can say for this condition, a probiotic is going to fix, fix the way you're feeling. So a lot of it has to be a little bit of trial and error. The thing that sort of bothers me most probiotics are very expensive. And I think the industry knows that people will pay the price for them. One of the big issues in the probiotic industry, and this is somewhat changing, but it's still a problem is when you get a bottle, and you look at how many bacteria are in there, like what bugs and then how many, often what they say is in the bottle, that number, the amount of bacteria was at the time of manufacturing, not when you take it home. So you may be paying $150 for 50 billion Cfu. But what you're putting into your body might be 10. Right? And so I don't like people being gypped for what they pay for. And, and then the other thing is a good probiotic, like a well manufactured product should always show the strain ID next to the name of the bug. So it'll say lactobacillus coagulans in parentheses, it should have a number or another identifier if it doesn't have that I would stay away from from that product. Just as a general guideline. The industry is changing bill in response to a lot of these criticisms, I think there are trying to be better. But what I say is you can achieve the beneficial effect of probiotics through your diet, through eating these foods that are eating a diverse diet, rich in fiber rich in fermented foods, you should not need a probiotic if you eat that way. And so that's generally why I say just do it naturally.
Nick Jikomes 1:10:27
I see. So there is an analogy there with like a multivitamin. If your diet is already good enough, you should not need that thing in the first place. Correct? What, um, what are some of the things that your lab is working on now, just general areas that you think are really exciting? Whether or not we we've solved any of the questions that you're pursuing yet?
Suzanne Devkota 1:10:49
Yeah, you know, my lab boy starts from a disease focus. So we look at, you know, the diseases where we think that there's a real microbial influence there. And then we weren't gonna dive into mechanisms and versus having maybe a tool and then applying it to a disease. So we're getting, you know, much more invested in obesity research. And the thing there that were we're studying and I alluded to this a little bit earlier is, I mentioned the early, early obesity, research was looking at sort of indirect effects of the microbiome on the host. So energy harvest, you eat a food, the microbiome metabolize it, and they provide more calories to the host. And that's why you gain weight. We actually think that there's a direct cell to cell interaction between bacteria and fat tissue. And so we're actually looking at it at that level. And we've identified some bacteria that can actually, you know, stimulate fat tissue to expand and grow. That's in the context of Crohn's disease. But we think those processes are actually paralleled in obese tissue as well. So that's a really interesting area for us. And we're using, we're studying patients who are undergoing gastric bypass. And we are collecting those tissues from those surgeries and looking at the fat and the gut tissue and seeing if some of these, you know, pathways are parallel, and what we are seeing in the other context. So so that's a very interesting area we're getting into. And if that holds true, there are some other diseases related to fat and organs. We're looking at sort of heart inflammation next, that we think microbes might also be involved. So that's, that's sort of our next, our foray are these bacteria that leave the gut and go to other parts of the body.
Nick Jikomes 1:12:46
Are there any final thoughts you want to leave people with just on this general subject of the microbiome?
Suzanne Devkota 1:12:54
Yeah, well, you know, I would say there is a lot of overhyping of this microbiome field. And I'm in it. And I can tell you, it's overhyped in many ways. So it is a critical part of your biology. It is important for many diseases, but it is not going to be the end all and be all of curing everything that all all that ails us. But I do think if you, you know, you at home can do things in your daily life. If you can support your microbiome through some of the things I mentioned through your diet. I do think you have a chance, you know, at preventing some chronic, you know, issues down the road. And, you know, and hopefully you'll have some health benefit there. I think, you know, just little steps in your daily life to support gut health, I think can have long term long term benefit.
Nick Jikomes 1:13:48
All right, Suzanne devkota Thank you for your time.
Suzanne Devkota 1:13:51
Yeah, thank you very much.