Written by Christopher Kelly
Feb. 19, 2015
[0:00:00]
Christopher: Hello and welcome to the Nourish Balance Thrive Podcast. My name is Christopher Kelly. And today I am joined by Dr. Les Dethlefsen and Christian Calma who is a research coordinator at Relman lab at Stanford University. Now, both of these guys are planning a new study into the human microbiota which I am planning on taking part in.
So guys, thank you so much for coming on. Do you want to start by explaining what the study is designed to show?
Les: Okay. This is Les. Thanks for having us on. As I am sure your listeners are aware, there's been a huge explosion of interest in the microbiota, how it affects our health. Our study is attempting to establish some of the baseline environmental knowledge, ecological knowledge that we need in order to make use of this knowledge.
So our study will be looking at the temporal variation, changes over time within a person that happens in the community of microbes that live in the large intestine, both when people are just kind of living a normal life and when there are some particular perturbations, disturbances. And we know just even sort of what you ate yesterday versus today can be a perturbation.
But there's also some more significant perturbations, if someone adds a very new item to their diet, in our case we'll be asking to add resistant starch as a supplement to their diet for five days as one of the perturbations. And a second perturbation in the study will be either a course of antibiotics, again a 5-day course of antibiotics or a colon cleanout which is sort of thing, not like the kind of New Agey detox type thing but what a gastroenterologist will have somebody do before they have a colonoscopy to really see out the colon.
So these three different perturbations are things that we know people experience, but we don't have a complete idea of how they may affect our gut microbes and we are looking at that.
Christopher: So how do you get to this point then? How did you decide, come to realize that these three things would be interesting in the first place?
Les: Well, think of any ecological location that you are interested, Amazon rainforest or your local nature preserve. It looks different now than it will six months from now. And if you were to say what organisms do I see now, you are going to get a different answer in a different time. Well, the same thing is true with the microbiota but it happens much faster.
So many of the studies that have been amazing interesting studies and they are still valuable that have looked at only a single time point from one person. We don't really don't know. Is that one time point an accurate picture of what their gut microbes are like all the time or does it change a lot?
We know enough to say that within a person, the gut microbes are probably more similar day to day, month to month in that person than they are to anybody else. But that doesn't mean that they are always exactly the same within a person. And what we don't have enough data on yet and anywhere, not just in the Relman lab, is to say what are the patterns and fluctuation over time, why do they occur, are there consequences like last week maybe you could have eaten any of those crazy food carts out front, it never would have bothered you but this week if you eat there, you're going to get a big diarrhea problem.
We don't know if those kind of things happened and we just need a basic variation. How do these things change over time? Some people have very stable microbiotas. Other people have highly variable ones. We don't know any of those basic questions.
Christopher: And do you know? You must have an idea of what's going to happen from previous work that's been done. Do you know what you're likely to see? Do you think the flora is likely to be really, really stable over time?
Les: We do. I have some ideas, some predictions. The disturbance of adding resistant starch to the diet has been conducted a few times before, not with the kind of detailed data that we're going to collect about the microbiota, but there is a small subset of microbial taxa that will almost certainly increase in abundance in response to people eating resistant starch.
But the best study that has been done in this found that I think out of 14 subjects, two people out of the 14 in a previous study did not have any numbers of that small group of microbes increase in abundance. Those bugs were apparently absent in those people, and those people also wound up not actually having any digestion, a little digestion with that resistant starch. Most of it just came out in the stool.
[0:05:18]
We don't know on the basis of the previous small study either the exact time duration of how fast these bugs can grow or how fast they will diminish when people quit the resistant starch. We got a pretty good idea it's going to happen quickly within a couple of days, maybe even just overnight, but we will have to see.
We don't know how many different bugs there might be. It might be that for every new person we add to the study there's a chance we'll find yet another microbe or type of microbe that responds to this addition of the diet. So there may not be just a small list that we already know about. There may be actually hundreds, and we have to look at more people to find out.
With antibiotic perturbation, we've got a pretty good idea that a lot of bugs will be perturbed and almost all of them will bounce back within a week or so. But which bugs bounce back and which don't, it looks like it may vary from person to person. And again, with such sparse data we can't begin to generalize yet and that's why we need more data.
Christopher: Okay. And so what do you think the problem is with the antibiotic? What's happening to the microbiota that's leading to negative health outcomes?
Les: Well, I have to say, let me start by saying that most of the time there aren't negative health outcomes. So I totally agree people should not be taking antibiotics unless they need them. We've got to reduce the overuse of antibiotics for all sorts of reasons. But having said that, people shouldn't be scared of antibiotics. Oh, my gosh. There's 50/50 chance that I am going to wind up with some horrible disease if I have to take antibiotic. It's not that bad. We know most of the time, most people taking antibiotics and there's no consequences that we can measure, no immediate consequences.
But the concern is that even if most microbes return to similar population level than they had before, there's few that don't come back. Are they important or are they not? Even if they play an important role and they don't come back, have they been replaced by something else that plays the same role? So it doesn't matter. Well, we don't know how often these problems may arise.
It could be that the relatively few times that there is a serious consequence of antibiotic use like C. difficile colitis, that that’s just kind of a roll the dice. If this one important function gets wiped out, yes, you're going to wind up with the C. difficile infection. But there are a hundred different organisms that could provide that function and any one of them if it persists or gets back into your gut, it won't be a problem.
That's kind of the clearest cut case we know about now with our knowledge where we can draw a direct line between something is perturbed in the gut microbiota, and there's this very serious disease as with the case of C. difficile. But there's a lot more subtle things that are probably going on too.
Ulcerative colitis, which doesn't seem like it has a strong genetic component, often occurs after some sort of disturbance to the gut, but it's not exactly clear that there's -- I mean it doesn't look like there is just one pathogen that causes ulcerative colitis unlike C. difficile. We don't know what exactly makes the problem arise. We know it's associated often with the disturbance in the gut microbiota. But we can't begin to put our fingers on mechanisms, and we don't know if there might be some magic probiotic that we could take to prevent ulcerative colitis. At this point, it's just an unknown.
Christopher: The other where I'm kind of interested. So we're going to drink this. This is what I am going to be taking part in. So I am going to drink this solution that's basically going to give me diarrhea. Is that designed to mimic exactly that, say, someone getting food poisoning? How is it different from the antibiotics?
Les: Well, the GoLytely solution you'll be drinking, when that was sort of developed as medical intervention, it had nothing to do with sort of studying changes in the microbiota. It was gastroenterologists that were putting a little tiny camera on a cable up into people's back sides to look for evidence of colon cancer or things like that, diagnose problems up there. The gastroenterologists said, "Well, gosh! We can't see anything if it's full. Let's empty it out."
[0:10:22]
This is sort of a polyethylene glycol stuff. It's just something that will draw a lot of water into your gut. Your gut will get rid of it, and it's just flushing out your gut and making the inside sort of clean and shiny and smooth; and so the gastroenterologist could look and easily see problems. For our purposes though, we can use this very well understood, very sort of low risk of side effects intervention as a contrast to the antibiotic perturbation because antibiotics in effect are selective poison.
A subset of microbes will probably get largely wiped out. There will be other bugs that depend on the first set; they'll also be diminished. And other bugs are essentially untouched by the chemical perturbation, but they may be perturbed by the presence or absence of their neighboring microbes. But it's a selective effect that's very strong for some, weak for others.
In contrast, cleaning out the gut with the GoLytely solution affects all the microbes. 99.99% of all the microbes are gone but it's non-selective. So we might expect a very different kind of response. Imagine, let's say, two different forests, one of which is a forest fire, almost every living plant is burned. And another one, there is a disease that wipes out two or three species of trees. That's the contrast between saying what happens when you just reduce all the biomass and then when everything come back or what happens when you just remove some of the key players.
Christopher: So it seems like it could be more dangerous than just having this reduction of diversity might be worse than just getting rid of everything. Is that what you think or is that not true?
Les: Well, we know that that is true in the sense that -- again, the clearest sort of disease that responds directly due to antibiotic perturbation is the C. difficile colitis and the risk of C. difficile colitis after the colon cleanout is quite low. We just know that lots of people got these colon cleanouts, and very few of them have the C. difficile problem.
So one of the questions is why is that? Why does wiping out the vast majority of the biomass but not doing it selectively, why doesn't that lead to the same problems as taking an antibiotic? And I have a theory. I have no idea yet whether it’s really true, but my intuition says that even though we've eliminated everything that's inside the gut in the center of the gut with that Go Lytely treatment and the colon cleanout, almost all the native gut bugs are still going to be present stuck to the mucus lining. There will be a small resituate population of all the important species that will be capable of growing back very quickly.
So within a short time, I think we will see the gut microbiota is going to get back to normal after the colon cleanout. That's my prediction. And because the entire community comes back, the C. difficile does not have a chance to get in and invade.
Christopher: Okay. Yeah. I was kind of expecting --
Les: That's by no means established but that's my intuition about what's happening.
Christopher: I think that seems really reasonable to me. I think that's what's going to happen as well. I mean surely it must be affected by your environment as well. If you would to move someone from one place to another at the same time that you just move everything, surely that would make a difference too. I am sure because I eat the same food as my family and because I am surrounded by that same variety, touch the same surfaces and all of that is going to make a difference. That probably leads to what you just said. Everything is just going to come back exactly the same as it was quite quickly.
Les: You are exactly right, and that's in fact -- I think part of the explanation for the observation that the risk of the C. difficile colitis for typically elderly frail people who take multiple courses of antibiotics, if they were living in nursing home or if they're in a hospital, that risk of C. difficile colitis is greater than if they are living at home or with their family. And part of that is that they may already be the spores of C. difficile around in the hospital or nursing home and part of it may be that, well, if they're back at home with their family, the same bugs that were in their gut before or kind of on the surfaces will get back in. If they don’t survive the antibiotic treatment, there's a chance of getting re-inoculated from your spouse, from your kids, from your dog, from the toilet handle.
All of that provides source of microbes that may be healthy whereas the source of microbes that you may get if you are in a hospital maybe more likely would contain pathogens.
[0:15:28]
Christopher: Okay. And then talk to me about the technology. This is quite fascinating, isn't it? because this type of study probably wouldn't have been possible even if you showed it years ago. So how exactly are you going to track the microbiota over time in these people?
Les: Well, you are exactly right that the technological development which is amazingly fast -- I mean even those of us in the field are kind of overwhelmed by how fast things are changing, we could not have done the study even a few years ago. There are four different technologies we're going to apply, and one of the innovating things about our study is that we're applying all four methods to all the samples.
Usually, studies have applied just one simplest method. Sometimes there are more advanced methods on some samples. The statisticians hate that. When they try to look at that data afterwards and say, "Well, we don't have enough information to really relate what we get from the more advanced study methods to the whole picture," well, we're going to try to bridge that gap in this study by applying both more basic and advanced technologies to every sample. So let me tell you what those technologies are.
Christopher: Okay.
Les: The easy one -- again, that would have been impossible 20 years ago but it's impossible for about 20 years -- is looking at a particular gene that's present in all bacteria called the 16S ribosomal RNA gene. A little fragment of gene sequence from that gene can give us a pretty good identity match for an organism. So it's like an ID card with no kind of the name of bugs by using this approach. So that's something where we can get not just which bugs are there but there are approximate relative abundance as well. Think of it as like a census. So that's the basic technology that gives us an indication of the composition of the community.
The second approach is called the metagenomics. It's again based on getting gene sequence information but it's not just from this one identity gene. It's from the entire genome. All the genes of all the microbial types that are present there in the stool sample will have a chance of seeing those in our data. So it's like getting a much more detailed picture, not just of the native microbe but what are the things they can do, what's their genetic capacity.
If you take the analogy of a human population, not just a census, a list of people and their names, but what's their complete job description? What are their hobbies? What do they do at home? All the things that all these people can do. So that's metagenomics.
The third thing is metatranscriptomics. A transcript of a gene is the messenger RNA copy that is used to actually make the protein that the gene is designed to make. So the messenger RNA levels tell you, oh, these are the proteins that the cell is actually making right now, not just what it could make but what it's doing. So the metatranscriptomics would be like a real-time video; picture like the satellite video that you could zoom in to any individual you wanted to say right now what's that person doing. Are they at work? Do they have these activities going on? Are they back at home gardening or sleeping? The transcriptomics will give us the immediate readout on their activity.
And then the fourth technology we'll apply is called metabolomics, and that is kind of looking at the chemical traces of all that activity. Most of what the microbes will be doing is their activities, because they don't have arms and legs to bike to work and type on a computer keyboard, the microbes that are active is by catalyzing chemical reactions. They make enzymes that make reactions happen faster.
So there are certain chemicals that go in, they're changed to other chemicals that go out, and the metabolomics gives us some measure of what are all the different chemicals in the sample. And with the chemicals change in concert with changes in the transcriptome and change in concert with which strains of microbes are getting more or less abundant, hopefully we'll be able to make a pretty good case. Here are the bugs that are present, here is their capacity of what they can do from their genome, here's what they're actually doing, and here's the chemical changes in the environment that resulted.
So hopefully, it's going to be a really thorough complete picture.
[0:20:17]
Christopher: It's amazing. And is all of that from a stool sample then?
Les: It is. It's remarkable how much information that we can extract. In our study, we'll also be looking at urine samples, not as we're looking at the microbes in the urinary tract at all but because a lot of the chemical changes that the bacteria in our gut are responsible, they actually don't happen in isolation. They may be very important parts of the human metabolism where enzymes in our liver or in our muscles or fat cells participate.
So the microbes carry out one part of the reaction then something gets in the bloodstream, goes to the liver, it carries out part two, it comes back, gets back in the gut, different microbe carries out part three. Well, in order to get the whole integrated picture of how the human plus microbe metabolism acts, a urine sample that we'll apply the metabolomics to, that gives us the whole body picture beyond just the microbial picture we'll get from the stool.
Christopher: Okay. Is that organic acid testing that you're talking about there?
Les: It includes that and goes much beyond. So when you say organic acids, I assume you're talking about things like the acetate, propionate, butyrate type of things.
Christopher: Yeah, exactly. So in our practice we run a panel by Genova Diagnostics, but I believe it was originally developed by Metametrix Lab. It has exactly 46 organic acids. There's a whole section on bacterial compounds, but I wasn't sure whether it was the same technology or maybe even the same test or something else.
Les: It goes beyond that in that there will actually be two different metabolomics technologies. They can detect these organic acids as well as many, many other things. One of the approaches can in fact detect thousands of different chemicals simultaneously. But the trouble with that approach is that you can see, ah, here's a unique chemical. I am seeing it here. I am seeing it again on this other sample. Sometimes you know what it is, but sometimes you don't know what the chemical is. You just know that you are seeing the same thing over and over. It's the second approach where you don't detect as many different chemicals but you do know exactly what each one is.
Christopher: So at no point then there's going to be somebody looking at something underneath the microscope. It's all done completely automatically. There's no traditional stool culture of any type.
Les: You're right. For our study, those older technologies which are still very important and very valuable, they are also so labor-intensive that we can't do a study of the scale that we're hoping to do and apply these technologies without kind of an army of technicians with microscopes or technicians using Petri dish cultures to implement them.
Christopher: Okay. And how many people are going to be in the study?
Les: Well, we're hoping to recruit well over a hundred people to participate in the various arms of the study which would be by far the largest study to look at detailed time courses from the human stool. It's unusual now for there to be studies that include hundreds of participants. but usually that's just one or a couple time points per person. But it’s not by any means going to be all the diversity of people, even a hundred sort of folks living in the US as most of our -- all of our participants will be US residents. It may give us a pretty good idea of what things are like for people in the developed world in the US but we know that there is far, far more diversity in the gut microbes of people around the world than we'll ever find here just in the US.
Christopher: I am just wondering, what's the draw other than in the name of science for people to participate in the study?
Les: Well, the biggest thing really is that hopefully people are excited and motivated to expand the boundaries of our knowledge, both just for the excitement of it but also because that really will have an impact on people's health in the way we can practice medicine in the future.
But the immediate benefit to participants from out study, well, beyond feeling good about yourself, we can't promise much. It is possible that you might look at your own gut microbiota because we'll provide the data. If you join the study, we will share all the data about your microbiota with you and you might look at that and say, wow, here's some microbes that actually tend to be abundant in people that eat a lot of meat. I thought I wasn't eating that much meat. I thought it was more kind of tending to the vegetarian side, but these microbes that are abundant in vegetarians aren't that abundant in my diet. Maybe I need to do a little better with my diet.
[0:25:12]
Or maybe if you think that having bifidobacteria is important -- which they certainly are usually a beneficial microbe. It's not clear that they're important for adults. They are most always going to be important for infants that are nursing -- but if you think, well, the bifidobacteria are important. I don't have a lot of bifidobacteria. I can go get a probiotic supplement. And that's the kind of thing that -- it's just at the edge.
As a scientist, I can sit here and say that we know enough to look at your list of which microbes you've got and prescribe a treatment to say you need to have this in there and you need to get rid of that. We don't know enough to be sure of making those pronouncements, but there is some suggestive evidence.
So if you are the sort of person that wants to follow the latest science and kind of take a leap a little bit and say, you know, I am convinced even if the doctor can't promise me this is a good treatment, I think I will be healthier if I try to change my gut microbiota this way, well, this study might give you the knowledge to start to do that. I am hoping that in a decade or so, maybe two, your physician will be able to do a test like this routinely.
As a preventative health measure, when you are still in your 30s, decades before some of these chronic diseases show up, your physician might say, "Ooh, look at your microbiota profile. It doesn't look healthy. We can predict that in a decade. You're far more likely to have this heart disease or develop diabetes because of this microbiota profile. Let's work on changing it." That's the goal but we're not there yet.
Christopher: That was my thinking is that these data might not be incredibly useful right now, but certainly in 10 or 20 years' time it’s going to be invaluable I'm sure. Tell me, is it just bacteria? When you say microbes, what does that include? Is it any protozoan organism or anything like that?
Les: Well, you are exactly right. The term microbe certainly means a lot of things beyond bacteria and our guts include things beyond bacteria. The bacteria are the largest part. In addition to the bacteria, which are numerically by far the most dominant, there's another strange category of organisms called Archaea and they look like bacteria. They are the same sort of size of bacteria. People until a few decades ago thought they were just kind of a special type of bacteria. It turns out that Archaea are like a whole different branch of life that are about as different from bacteria as we are from bacteria.
So you have the three main branches of life, eukaryotes which is like plants and animals, any living things you usually think of, seaweeds, a lot of single-celled protozoa, they are eukaryotes. Then you've got Archaea and then you've got bacteria. Three equally different divisions. In our guts, most things are bacteria. There's one type of Archaea that are present and they are the things that make nothing. They are methanogens which in some people is actually a pretty important metabolic process.
And then there are things like yeasts, protozoa, various single-celled organisms that for the most part yeasts are actually a normal part of the gut microbiota. The other single-celled organisms, it seems like they're mostly pathogens. And so in the developed world, most people don't have them and when we see them, it's a sign that something's wrong and oftentimes it comes along with disease like amoebic dysentery or giardia. People are having a massive diarrhea and it's not a good thing. It might be that in other parts of the world there are protozoa that are just naturally present without causing disease. It's one of those questions we haven't answered.
But the other type of microbe that's really important to think about -- some people would call it a microbe, some wouldn’t -- are the viruses. There can be a lot of viruses that are present without causing disease. There are viruses that attack the bacteria, and they can become important because maybe the viruses that change bacterial populations that don't affect human health. This very much an unexplored area of science that people are now saying, "Wow, we got to look at this."
Christopher: So just to be clear then. So will the testing classify all of those types of things that you just talked about?
Les: No. We'll have the ability to see all of those different types of things in the metagenomic sequencing. But the reality is that the abundance of things other than the bacteria and the special kind of Archaea called methanogens, other than those organisms, the other components are rare enough that we will be able to learn a lot about them. The types of technologies you have to apply to get at those other types of microbes are different enough that it would add a whole another -- it would sort of double the complexity of the work we have to do to examine all of them.
[0:30:33]
Christopher: Okay, I understand. And so what are the hopes for the outcome? What's the goal? Is it to produce a new type of antibiotic or something else?
Les: No. We certainly aren't looking to be able to produce a type of antibiotic. We definitely believe that our work will have an impact on human health. But it won't be the sort of thing that we provide a new treatment or even a new sort of magic preventative thing, a new probiotic that says, hey, this thing, take this, it will keep you healthy. It's more providing a context.
Again, ecological analogy is exactly spot on. If you go to a new place, you show up on an uninhabited island, in the tropics, all kinds of species of stuff going on there and you think, "Wow, these are really cool. We can use this stuff." And you start sort of cutting down trees or hunting a certain animal because it's got great fur or beautiful feathers, whatever. You don't understand the ecology of the place you are disturbing.
Maybe what you are going to do is greatly devastate an ecosystem because you simple don't know that this one species that doesn't seem to be that important as in fact the key to the whole thing. If you understood and you could sort of manage your use of the ecosystem more intelligently, maybe you can get all the benefits you wanted and maybe the ecosystem still healthy and functioning.
But you need to have the knowledge of how the ecology works to do that. And what we are hoping to do with our study is really fill in some gaps in our ecological understanding of our own internal ecosystem, specifically how it changes over time, perhaps why it changes over time, what are the different patterns of change over time in you, me, other people.
That ecological understanding is what will let a physician perhaps in the future to say, "Oh, look at this. We've got you scheduled for this surgery but your gut microbiota look like they're kind of in a fragile state. We’re going to have to pay particular attention to you for this reason." Whereas in a different situation, "Okay, you're going to take this antibiotic but the tests show that you are going to tolerate it just fine. We don't have to worry about consequences for you."
Christopher: So is your understanding then good enough to be able to give recommendations to the people that are taking the GoLytely solution or the antibiotics or is that part of that study that they mustn't do anything like take probiotics after that treatment?
Les: Well, we're kind of walking a fine line here. In my role as a scientist based on sort of confident knowledge from the research, what could I tell someone? I am not a physician, I should say that. If I were a physician, what would I feel like I could confidently tell a patient? That may be different from what I would do myself. You're willing to go out on a limb a little more.
Christopher: I want to know what you do.
Les: That's a very good question. Would I have to take an antibiotic? which I did just recently, I am very likely to take a probiotic during the period when I am recovering from that, during and after the antibiotic for a while. I don't take probiotics all the time. I am not convinced that kind of taking those things routinely is important, probably not even helpful. But when there is a perturbation with antibiotics, there is some good evidence that the probiotics can help force all problems. So I take them then.
It is probably true; if somebody were to say, "You know, I just really think the probiotics help," I am not going to try to talk them out of it because the probiotics are so unlikely to cause harm that even if they don't do much, if you think they're going to help you, go for it.
The best advice I can give you or anybody -- and this is true whether it's after a perturbation or just through your life, I don't need to know what's in your gut already to give you this advice -- eat a healthy diet and you will not be surprised to learn that it's the same health that people have been talking about a long time, a diverse diet, a lot of plant material, diversity of plant fiber, low on the refined things and the sugar. It is true, the older advice about, okay, it's got to be low fat. A healthy diet is low fat. That's pretty much being called into question. It doesn't seem as though certain fats are harmful. It's not the fat itself.
[0:35:17]
Red meat and saturated fats are definitely a bigger problem. But it's not like they're poisons, I don't think. Evidence shows that in moderation young meat in the diet, I don't think, is a sure problem; but I do think the presence of a wide diversity of plant fibers for your gut microbes is probably the single most important thing you can do.
Christopher: So you don't differentiate then which types of plant material. So there's nothing special about, say, the starchy storage [0:35:49] [Indiscernible] or anything like that. You don't need to be eating those to have a healthy microbiota.
Les: Well, in a sense, this is where our knowledge is really not yet adequate. There may be some important subgroup of bacteria that really specialize on things that tend to be found in starchy root vegetables. That's why I said a diversity of plant types. I am not saying out of the whole diversity that exists, you can pick the one or two you like and focus on those and it will be just as good as somebody else who focused on a different two or three plants. That's not my picture at all.
That could be true but I suspect instead the cases that if you eat a wide diversity of different plant types, all the different beneficial bacteria will have a chance to survive and persist. So just like the ecosystems in general or diversity is seen as a good thing in your diet, I think diversity is a good thing too. So don't eat all of any one thing.
Christopher: Right, that's makes a lot of sense. So if I was just eating a lot of processed food and there wasn't a lot of variety of plant materials to feed the microbiota, why would it not work then just to take a probiotic supplement? What would happen, do you think? I know we don't know this for sure.
Les: Well, actually, that question I can answer pretty definitively and let me answer it by analogy. So some probiotic supplements you take are really just a single strain of bacteria and the more advanced ones may have a couple of strains or even I've seen some that have a few dozen strains. But let's say you've got the best probiotic you can buy in the market. It's got 30 different bacteria in it or even a handful of different yeast species, something like that. If you went to this -- let's say a deserted island where there's no life, it's just naked dirt, soil or whatever, and you could have 30 plants. Would you be able to recreate, say, the Amazon rainforest or even your garden out back? The diversity you can get from the probiotics is nowhere near the diversity that exists naturally.
What's more, if you are eating that processed food diet, it would be like, well, we aren't providing that things these plants need. It would be like scattering those 30 seeds on an asphalt parking lot. If you don't provide the environment that those organisms need to survive, it doesn't matter if you are swallowing live organisms or not. They aren't going to make it.
Christopher: That makes a lot of sense. And so it wouldn't make any difference then if you would just tap -- I've been looking at a new probiotic where they've taken sort of like an ancestral health perspective. They've looked at the types of bacteria that exist in fossilized specimens of various origins and said, okay, well, these are the microbes that are missing from our guts. If we create a probiotic that contains these missing microbes, then we're going to do a much better job. So you think that still that's going to have the problem then that you wouldn’t -- I mean all of the things you just said just didn’t apply, right?
Les: Yeah. And I have to say I respect that approach that you just described. I think I've read about that as well on the web and I have to say, okay, these people are thinking more than superficial level. That's the kind of thinking we need that will help us make progress. Again, taking the probiotic supplement like that is very unlikely to cause harm. If it turns out that you're missing an important microbe and that probiotic has it, it may be that that probiotic really does become a key to restoring health for you.
So I don't want to sound as though I am being dismissive towards it, but it's also true that a typical human may have hundreds at least of different strains of microbes that are in moderate for high abundance and thousands of different strains if you count all the things that are rare as well. We don't yet know whether you only need, let's say, two dozen important microbes and you'll be fine or whether you really need all thousand.
[0:40:09]
And until we have a definitive answer to that and I think the likelier answer is the greater diversity does matter. I wouldn't be confident in saying that a probiotic, even if it was very well researched and the couple dozen strains that included really are things that are healthy, that were present in our ancestors, that are present today and people who we know are healthy, that the two dozen best strains you can pick are still not going to provide all the things that will be provided by a native community of a thousand strains.
Christopher: I don't think this is going to be very hard at all to get. So I know that in over a hundred of people that are probably listening to this who have paid me to run a stool test to try and find pathogens like C. diff and we have found some things like that and it’s really improved people's health by doing this sort of testing. So I think there's a lot people listening that are going to want to jump on this and get involved in this study to have that data. So what are the logistics? How do I get involved?
Les: Well, thanks very much for pointing it out. And let me turn this over now to Christian Calma who is the study coordinator. He will be able to answer those questions better than I can.
Christopher: Okay.
Christian: Hi. This is Christian. So I am the research coordinator for this study. Chris, we actually talked earlier. So if you remember the process of enrolling, you probably stumbled across out web page and followed through the facts section, the frequently asked questions section. And at the bottom, there is actually an eligibility survey. So some participants are screened out depending on if they've taken antibiotics recently or if they've traveled or -- what else?
Les: If they've been hospitalized recently, if they have a chronic medical condition. If you are basically healthy, there's a very good chance you'll be eligible for our study.
Christopher: I think that's true to most of my listeners. They're mostly athletes that are just looking to improve their performance. So yeah, I think that most people listening to this will be eligible. So that's really interesting. So how does it work logistically though?
Christian: That's great. Okay. So once you are done filling out the eligibility survey and you are eligible, I will contact you to fill out the consent form. During this process we'll actually build a sampling calendar. This sampling calendar details pretty much the next 25 to 36 weeks of your life. So I guess that's what's different with our study in the sense that it goes on for months' long time.
But logistically, once you are enrolled and you get this consent form and we've built your calendar, you'll get mailed this box full of stool sampling supplies basically and urine sampling supplies. Essentially, you'll have to store your stool and your urine. You'll have to collect it yourself also. Then you'll have to store it in your own freezer for until every 25th sample and we'll send -- depending on where you live, if you live close to the Palo Alto area, we can actually just visit you, pick it up, and bring it back to the lab. But that doesn't mean that if you live farther away, if you live in Texas, for example, we have a whole dry ice system where you'll just load your samples into the dry ice box and we'll arrange for UPS to pick it up and send it back to the lab.
Christopher: So will people be collecting every single day then?
Christian: No, not every single day. But there are periods of times where it will be -- so the most intensive period is during the perturbations. So for the diet perturbation, that will be five days of supplementing your diet with this resistant starch. So it's five days straight of sampling with a week. The week before it's straight sampling and a week after it's straight sampling. So that's 19 days of straight sampling. So that's just specifically around the perturbation periods. But more regularly you'll just be sampling on a weekly basis.
Christopher: Well, that's not too bad at all. When does the study start then?
Christian: The study started already. So it's more whenever we get participants in who have signed the consent forms and we built their boxes. And it all gets kind of worked out during the consent form meeting process.
Christopher: Okay. It doesn't really matter. It's not like these people would have to do the test, the whole thing in parallel, right?
Christian: Oh, no. And we can also plan around. So say, for example, like we have a lot of participants who have to go to conferences, for example, or maybe for listeners of this podcast who have races, for example.
Christopher: I was just going to say I am going to do a 7-day stage race across Canada and I am wondering...
Christian: Oh, that's interesting. I am actually from Canada so tell them hello. Anyway, yeah. So for things like that, we can actually plan your schedule. So for example, you wouldn't have the sample around the perturbation periods or at least put in gaps where you don't have to bring your stool sampling supplies on the plane.
[0:45:13]
Christopher: Okay. That's great. The final question I have for you is I am just wondering how you are going to know what was the kind of the disturbance that you made and what might have just happened anyway. So to get back that example, say, I go to Canada and I do a bike race and I spend three hours a day removing the blood supply from my gut. Isn't that surely going to have a similar effect as any of the other sort of perturbations that you've been talking about? How are you going to know what was cause and effect?
Christian: Sorry, Chris, I forgot to mention one thing. So in addition to filling out, so participants will be asked to fill out questionnaires and collect stool and urine samples. But in addition to that, there is this one last piece where there's actually a participant journal. And through the journal, you'll actually be logging when you sample yourself. So you'll mark the day of the week, the samples you have collected, and you'll also be marking strange little occurrences that may have occurred during the day. So say, for example, if you had an upset stomach --
Les: Or a stage race across Canada.
Christian: Right, stage race across Canada. You'd be logging this in the participant journal too.
Christopher: Okay. Then the other thing I was wondering about, so I keep attacking on more questions. Is the resistant starch -- and so my original experience with resistant starch was not good. I read about the stuff, read about some of the potential benefits, almost quite sold on it. I probably went a little bit too quickly at the end too fast. But in the end, I had to go really, really, really slow. And now I can handle four tablespoons of resistant starch no problem at all but it can be a long time to get there. So I am just wondering about all the participants of the study, are you going to have a massive dropout rate when they get to day two of four tablespoons and they're blown up like a balloon. Is that going to happen?
Les: Well, I have to say certainly you aren't the only person to have this effect, but many people don't. For example, I did without having sort of built resistant starch, I wound up going straight into from the zero to four tablespoons a day which is the dose we'll be asking people to take. I didn't have those problems. Maybe it's because I already had a wide diversity of plant fiber in my diet and a lot of it. If necessary, people can deal with what you've said which is just sort of add it gradually to their diet.
So if people really are "Oh, my gosh, I absolutely cannot tolerate this at all," well, we can note that and that becomes part of the information. Maybe we’ll be able to -- if you've got three days into what was going to be five days of perturbation and you just say, "All right, that's it. I cannot tolerate this," or "my partner cannot tolerate the gas."
Christopher: Or the co-workers at the office.
Les: That's right. Then obviously stay in touch with us. Obviously, we're not in charge of your life and say, "Okay, we'll note that in the participant journal. We'll pay attention to what bacteria looked like they were becoming abundant in your gut at this time." We might have some answers at the end of the study top say, gosh, if these bacteria are becoming more abundant when you eat the resistant starch, it's tolerated and just perfectly fine. People don't describe any problem at all and describe feeling better and more energetic. Whereas if these other strains are the ones responding to resistant starch, holy cow, look out. Those are the folks that have these problems. We may be able to make those inferences from exactly this kind of information.
But really you bring up an interesting point. We don't think this is a very high risk study, but at any time you should not be doing anything in the study that is compromising your health and safety and happiness. So the study, of course, is voluntary. If things are getting out of hand, let us know. None of these perturbations or the sampling are essential. If you need to drop out of the study, we understand. If you need to change things somewhat to make it fit into your life, we understand that too.
Christopher: Okay, brilliant. Well, I think it's an amazing study and obviously else I wouldn't be doing it. I mean it makes all of the tests meaningful. Unless you know what to do with the results, then what's the point in doing the test? I think this is obviously really clearly an important study to figure that stuff out. So I really encourage everybody to do it. Obviously, I'll link to it in the show notes for this episode and people can get in touch with Christian that way. Hopefully, we'll fill it in no time at all.
Les: Well, thank you. We appreciate very much your enthusiasm and your willingness to share it with your listeners. I'll say that in addition to the website, our website you link to, we did an AMA a while back. You can find that. There may be questions people have that I've already answered there. If you want to get in touch and just say, "Hey, what about this? What about that?" beyond, just the details of the study itself, let us know. We've got information about the microbes on this website. People ask a great question, we'll answer it and put it up on our website and share that with everybody.
[0:50:30]
Christopher: Okay, sounds good. Yeah, I will link to that. What does AMA stand for? I just found that page and read it, and I don't know what AMA stands for.
Les: It's Ask Me Anything. There I was responding in real time to some wonderful questions from people all over the cyberspace. It was fun and exciting and I hope really helpful for people to get answers about their gut microbiota.
Christopher: Awesome. I will link to that too. Well, Les, Christian, thank you very much for your time. I really appreciate it.
Les: Thank you.
Christian: Thank you so much, Christopher.
Christopher: Cheers. Bye-bye.
Les: Bye-bye.
[0:51:05] End of Audio
© 2013-2024 nourishbalancethrive