How to Optimise Your Gut Microbiome [transcript]

Written by Christopher Kelly

Sept. 19, 2019

[0:00:00]

Christopher:    Well, Lucy, thank you so much for joining me here at the Ancestral Health Symposium. 

Lucy:    Yeah, thanks for inviting me to be on the podcast. 

Christopher:    We've known about you forever and for some reason, it's taken this long to get you on, so thank you. Tell me about your talk this morning, microbiome testing. Is any of it worth it?

Lucy:    Yeah. I spoke today about evidence-based microbiome testing and therapeutic strategies. I do think that testing is worth it. We're learning more and more about the microbiome, but there are definitely certain tests that are better than others. One of the things I talked about this morning was how culture-based tests really aren't accurate in terms of the fact that they only represent about 4% of the microbes in the human gut that you're getting back on the results and also tend to skew the bacterial abundance, so we really need to be moving towards sequence-based tests, which is what we know from the research and where all of microbiome research is going as well. It has really been this movement towards sequencing. I think practice has been slow to follow that, but it really needs to make sure we're there too.

Christopher:    Well, let's get into that in a little bit. Before we go there, why don't I ask you how you became interested in the microbiome in the first place? Obviously, you think it's important. There are a lot of things you could talk about, but you chose to talk about the microbiome. Why is that?

Lucy:    Yeah. I had chronic eczema pretty much my whole childhood through undergraduate studies and ate pretty much whatever I wanted to, junk food diet, and it really wasn't until I came across the connection between nutrition and skin health. 

Christopher:    How did you come across that connection?

Lucy:    It was actually my older sister who started getting interested in nutrition and whole foods, kind of more ancestral diet and -- 

Christopher:    Did she have similar problems?

Lucy:    No. It was more just a general interest in health for her that she just became enlightened about the connection there and started giving me information. I was definitely very hesitant at first, but when I started making changes in my diet, I saw benefits for my skin. Then I started learning about of course the thing that mediates what we eat and how that impacts our skin health, is the gut microbiome. 

Christopher:    It's the microbiota, right. 

Lucy:    Yeah, so I became really interested in that. I did some research on food allergies and the gut microbiome in my senior year of undergraduate and I decided that that's what I really wanted to study. 

Christopher:    Okay, and what was your undergraduate?

Lucy:    Biology actually with a concentration in neuroscience. I went to a very small school, Kalamazoo College.

Christopher:    Okay, so tell me about your post-doctoral work. 

Lucy:    I just finished my doctoral degree in Nutritional Sciences where I studied the effects of diet and exercise on the gut microbiome. 

Christopher:    Okay, and am I right in thinking that you've been doing some work for Chris Kresser?

Lucy:    Yes. I've worked for about four years for him as a research assistant.

Christopher:    Okay. Can you tell us anything about the work that you do there?

Lucy:    Yeah. I've helped him create some content both for articles in terms of doing some of the research for that. I also did a lot of the nutrient modules for his ADAPT Health Coach Training Program most recently. 

Christopher:    Oh, that's great. 

Lucy:    We're potentially working on an advanced course in the future. 

Christopher:    Okay, and an advanced course in health coaching or in microbiome?

Lucy:    In GI, in microbiome. 

Christopher:    Okay, very interesting. What do you think your eventual career trajectory would be? I know you've talked about you're going to become a medical doctor. You're on the premed path now. 

Lucy:    Yup, so I'll be starting medical school next August. I'm in the dual degree program, RD-enrolled, so I'll be starting that in August. I already have quite a large client base that I help with both digestive issues and skin conditions, educating them about different testing options, therapeutic strategies that they can test out under the care of their physician. I'm hoping they really just build that out going forward and also be able to do research that really changes paradigms, brings more microbiome and nutrition into conventional medicine. 

Christopher:    And that's independent of Chris Kresser, right?

Lucy:    Yes, exactly. 

Christopher:    Okay, so why the heck would you go get a medical doctor qualification when you already are perfectly capable of helping clients? It's a cash-based practice, so unless you want to take insurance and prescribe drugs, I just can't see any reason why you'd become a medical doctor. 

Lucy:    Well, I think the way to really be able to shape changes in healthcare is from the inside and having the credibility of a medical degree will ultimately help me do that. I really enjoy learning and I have just a curiosity in pursuing medical school and learning more background that could potentially help me. Lastly, I do see some clients where it's really beneficial for them to have both an integrative approach incorporating diet and lifestyle, but in the short term, they may need some pharmaceutical intervention to kind of help quell information and be able to manage symptoms. When I first came into the ancestral health space, I swung really hard away from the conventional medical space and said I'm never going to touch drugs again. 

Christopher:    Oh, really? Why was that? Was there something in particular that -- 

Lucy:    Well, I really just feel like for so many years, I've seen allergists, dermatologists, all the specialists, and no one was looking at it from an integrative approach and I never got anything but a band aid for my symptoms, so this is what has not worked for 19 years. I'm going to go totally the opposite direction.

[0:05:11]

    I feel like I've come to a place now where I swung back to a more nuanced, balanced place where we can take the best of both worlds and bring it together. That's why I feel like it'll still be beneficial to have that medical degree so that I can bring together the best of both worlds for patients who need both aspects. 

Christopher:    Yeah, good answer. You reminded me of an experience I had with a dermatologist where I think I had a rash of some sort on my skin. It was no doubt related to my gut health. I've had all kinds of gut problems in the past. I sat in the waiting room for a while and then eventually I got to see the doctor. The doctor spent two seconds looking at the rash and said, "Yeah, that's fine. Just collect your tube on the way out." They had this bowl of like Ziploc bags, but I think it was just hydrocortisone cream. There was a whole bunch of people going through exactly the same process. Just pick up your Ziploc bag full of hydrocortisone cream on the way out and if it doesn't work, come back. The doctors are just looking at inflammation on the skin. They have no really idea of what the cause is, but the remedy or the treatment is exactly the same for everyone. I'm guessing this guy doesn't understand the process that led to this rash, but actually, the cream did work really well. You can't really argue with that. There's obviously something there. 

Lucy:    Yeah. I think when we get too far into the ancestral health space, we can try to avoid even something that might be beneficial acutely. Modern medicine is great for treating acute things and sometimes it can be beneficial to take something or use something topically in the short-term even if we then work to get away from that and do more diet lifestyle, supplementation, et cetera. 

Christopher:    Oh yeah, I've absolutely tried all the natural remedies. I've been through the full essential oils sales kit by the time I went to the dermatologist and yet none of that stuff worked. Well, let's talk about the microbiome. Perhaps we might start by -- can you make the case? Why would anyone care about this in the first place? Why would I want to do a test in the first place?

Lucy:    There's a lot of emerging research about the microbiome. It's a really exciting space. We've learned that the microbiome is not only important for digestion, immunological health, cognitive health, but has also been connected to virtually every chronic disease that we know has been associated with some kind of disrupted gut microbiome. In some cases, you can argue whether that's a cause or effect, but there are a number of animal studies where they've transplanted the gut microbiome from diseased humans into mice that essentially haven't seen a microbe in their lives. When you do this, you see the mice take on the phenotype of the human donor. They've shown this with obesity, with depression, so this really suggests that there is a causal relationship between changes in the gut microbiome and health outcomes and disease.

    As we're learning more about this, as we understand a little bit more about what a healthy microbiome might look like or certain characteristics of a healthy microbiome, we can potentially use testing to strategize different interventions or just understand what's going on in terms of the pathology.

Christopher:    I've heard some researchers who I very much respect say things like, "Well, nobody knows what a healthy gut microbiome looks like" then I've heard a response to that from other researchers saying, "Well, maybe you don't know what a healthy gut microbiome looks like," but let me ask you that question. Do you know what a healthy gut microbiome looks like?

Lucy:    I don't think we do. I think we can start to say we know some characteristics that generally speaking in most people tend to associate with health. For example, increased microbial diversity tends to be associated with health. However, there are definitely exceptions where people have really high diversity of a whole bunch of pathogenic microbes and certainly have tons of gut symptoms and certainly can be classified as a healthy microbiome, so there are certain characteristics like that. We typically think that butyrate producers tend to be pretty important for a healthy gut microbiome, but in terms of people looking at specific bacteria, a lot of people think -- bifidobacterium, for example, is a characteristic of a healthy gut, but the Hadza hunter-gatherers don't have any bifidobacterium and a lack of chronic disease, so I've generally said that a healthy gut microbiome is probably the gut microbiome you have when you're healthy. 

Christopher:    That's a good answer. 

Lucy:    That's honestly the best answer that we have right now. I think we're learning more in this space, but I'm always careful to recognize that there's a lot of interindividual variability in the gut microbiome, and so we can't easily be creating reference ranges for certain gut microbes because --

Christopher:    We just don't know that yet.

Lucy:    -- we just don't know that yet. 

Christopher:    I say "we" like I'm somehow involved in it, but I'm actually not involved in the research. I sometimes wonder whether via negativa is helpful, this idea of I can't tell you what's good or I can't tell you what I want, but I can tell you what I don't want.

[0:10:01]

    A via negativa approach to the gut microbiome is like I don't want giardia there and I don't want cryptosporidium there probably. I probably don't want H. pylori there. Is there a list that's in your mind that you can think of right away like I really don't want that?

Lucy:    In general, yes. There are certain ones like I would put giardia in that boat, cryptosporidia, so there's definitely some -- and that's where testing comes in because you can identify these parasites or pathogens that definitely probably shouldn't be there, but then there's also some that are more of a gray area like blastocystis hominis is a common parasite, and in most people, it's completely asymptomatic. 

Christopher:    Right. It's commensal, you might say. 

Lucy:    Right. There's some evidence that we evolved for years with parasites and helminths and potentially the rise in autoimmune disease is related to the fact that we don't have these organisms anymore. 

Christopher:    Right. In the absence of proper stress, the immune system gets busy with something that maybe it shouldn't. 

Lucy:    Exactly. 

Christopher:    Have you looked at the subtypes of blastocystis? I know there's a large body of research now looking at the different subtypes. Have you seen any clinical tests where it will tell you the subtype?

Lucy:    I haven't seen any tests yet. There definitely seem to be different subtypes of blastocystis that are more virulent than others. Unfortunately, we don't have any tests yet that I've seen that are commercially available to determine if you have one of the virulent subtypes, but I hope someone comes out with one soon because sometimes it's really hard to determine whether it's worth treating that or not especially if you have extraintestinal symptoms that could be related to blastocystis hominis if you have a pathogenic subtype like acne, different skin manifestations especially, but also those could be related to a number of other things like hormone imbalance, so sometimes it's hard to tease that out. I hope we see more tests in that space. 

Christopher:    I did the Viome test and I really can't tell you anything about that test. Our main criticism, Tommy included, is there's no transparency like they're not going to tell us what the hell is going on over there, but when I got the report back, it did report a blastocystis subtype. That was quite a surprise there. A cursory look at the literature told me that that was one that you really didn't want. I actually got some value out of this thing, but yeah, who knows how that test works. I just can't tell you anything about it. 

Lucy:    Interesting. I have looked at some Viome tests. I think unfortunately -- it's interesting that you say it can potentially look at subtypes, so I'll have to look into that. 

Christopher:    That's what they reported. 

Lucy:    I have to look into that specifically a little bit more, but in general, I find that in my opinion, metatranscriptomics, we're definitely moving there and more and more research is being done using metatranscriptomics, but we don't yet have the databases or the body of literature to be able to compare metatranscriptomic data that we get from patients or clients with literature to be able to create actionable information. At least that's what I determined when I last did an analysis of the various stool tests and microbiome tests available, but I'll definitely have to look into more of the subtypes. 

Christopher:    It's coming. It's a rapidly changing area, I'm sure. Is there anything I really don't want at the bacteria level? Is there anything you can see with 16S testing? This is the type of test that you uBiome for example offers. Is there anything you can see at the phyla level like proteobacteria or bacteroidetes or maybe something else that you can look at and say, "Oh no, I don't like that," a level of proteobacteria, for example?

Lucy:    Yes. Proteobacteria is one of the main red flags that I look for when I look at uBiome. Proteobacteria has been associated with inflammation. There's actually some really interesting literature that's come out recently that suggests that what might drive the expansion of proteobacteria is actually oxygen leakage into the lumen of the gut. So essentially, when your colonic epithelial cells that line your gut are starved for energy potentially because they don't have enough butyrate to fuel them, when you have colonocyte energy starvation, you actually get a leakage of oxygen into the gut lumen. Of course, the colon is supposed to be a completely anaerobic environment that favors butyrate producers, beneficial lactate fermenters, et cetera, and it's not supposed to have much oxygen at all. So when you have this oxygen leakage, proteobacteria has a lot of what are called facultative aerobes, and so they can grow on that oxygen and they outcompete all the other bacteria that can't or is poisoned by oxygen essentially. That might be what's driving the growth of proteobacteria, so we definitely don't want to see high proteobacteria. When we see that, it might be a sign that your colonic epithelial cells are starving for energy. 

Christopher:    Do you have a way of quantifying the level of proteobacteria? I know you know I know Jason Hawrelak and I've done his Meet Your Microbiome masterclass, which I very much enjoyed, and I know that there are no references for his reference ranges.

[0:15:07]

    He'll name some very specific levels at the phyla level in particular and I know he's very open about it. He says, "Look. I don't know it's actually what this should be. It's very fuzzy," but I like having a definitive answer. There are too many scientists out there, Tommy included, saying "however", "associated with", "likely", "probably", all these indeterminate words. I like that he's putting his head on the block and saying, "You know what? I don't think proteobacteria should be above," whatever it is. I forget what it is now. He said like 8% of the ecosystem or something. I forget --

Lucy:    It's usually more like 3%.

Christopher:    Oh, is it three?

Lucy:    Below three is typically more associated with health -- 

Christopher:    I never see them that low.

Lucy:    Really?

Christopher:    Yeah. I remember that seeing a bunch of people eating a high fat, ketogenic, sometimes carnivore diet, so maybe we should get into this then. If I care so much about butyrate, what the hell is butyrate? How do I get it? Where does it come from? You can even buy it as a supplement. Would you recommend that?

Lucy:    Butyrate primarily comes from the fermentation of dietary fiber by normal, commensal gut microbes. We can supplement with butyrate and I think there are some cases where that might be beneficial especially if you have an ongoing issue of gut inflammation or perhaps you have some evidence of epithelial energy starvation where that butyrate could be beneficial in overcoming that. I think there are some instances where butyrate supplementation is founded, but there are some caveats. I think there are issues potentially with providing supraphysiological doses of butyrate as a lot of people are taking especially --

Christopher:    Oh, really? There is something I feel like it's quite an obscure supplement. I thought there was some question of whether they even made it to the colon intact. 

Lucy:    Yes, absolutely, so some of it may be absorbed higher up in the gut where it shouldn't be if you're giving it in large doses orally. There are some companies that have made butyrate that's more targeted to the colon. There's one company -- I have no affiliation with them -- Tesseract that's created ProButyrate, so that's kind of my supplement of choice because it's targeted to the colon and it's a more slow release, so it's potentially more of a physiologic effect than providing a Cal-Mag Butyrate supplement at 5g dose, which is often what's provided on the labels for those. 

    I've written about this, but essentially with the inflamed gut, if you provide too much butyrate to an inflamed gut, you can potentially inhibit stem cell proliferation and wound repair. 

Christopher:    That is interesting. 

Lucy:    There've been some interesting studies looking at that. 

Christopher:    What's the mechanism? Is it too much acidity? How does that work?

Lucy:    Well, essentially in the colon, you have these crypts. Basically, it's kind of like a U-shaped dip --

Christopher:    Also like the villi. 

Lucy:    Yeah, so similar to the villi in the small intestine. The stem cells lie at the bottom of the crypt and the stem cells are more sensitive to butyrate, but in a healthy gut, you have all of the cells at the top of this U that are metabolizing the butyrate, and so you have a butyrate gradient that goes from high at the top of the crypt to low towards the stem cells. The stem cells normally aren't exposed to high amounts of butyrate, but if your cells at the top aren't absorbing butyrate, well, then you potentially have higher amounts of butyrate coming into contact with those stem cells and inhibition of proliferation. 

Christopher:    Okay. How the hell can anyone know this? You're talking about an anaerobic environment. How did someone figure that out? Obviously, they didn't do it inside of a human. They did it in a Petri dish, but even then it seems challenging to know that. 

Lucy:    Yeah. Typically, they've done it with mouse tissue. They can actually isolate it and then what they do is they can stain it with a Hypoxyprobe so they can actually see fluorescence where there's a lack of oxygen, so that's typically how it's measured. I haven't seen any studies yet that have been able to look at this directly in humans, but I think there's potential to do it with biopsies at least in terms of the oxygenation of the mucosa. 

Christopher:    So for the general listener then, somebody that doesn't really have a bunch of gut pathology, you'd recommend a plant-based diet that had lots of fermentable substrate. Let's call it microbiota accessible carbohydrates, to take a term from Justin Sonnenburg. Is that what you'd recommend for people in general?

Lucy:    In general, I think it's beneficial to get a wide variety of different types of fiber. I will say that I don't really think there's one diet that works for everyone. I think it's beneficial to experiment. Some of what I presented on earlier today was that actually, on a ketogenic diet, you may have a reduction in butyrate because you're not getting quite as much fiber when you're limiting your carbohydrates, but if you're in ketosis, you have beta-hydroxybutyrate and acetoacetate in the blood.

[0:20:02]

    Interestingly, these are actually intermediates in the butyrate metabolic pathway, so they can essentially -- I've hypothesized that they can make up for potentially lower levels of butyrate during ketosis. You also have -- 

Christopher:    Has anyone looked at that experimentally? Does anyone know? 

Lucy:    No. I'd love to.

Christopher:    The molecules kind of sound the same. They have some things in common, but do you know how much butyrate is there? What's the concentration like versus what's the concentration of beta-hydroxybutyrate in nutritional ketosis? Is it even theoretically possible that BHB could take up the slack?

Lucy:    I think it is and it's something I really, really hope to study in the future. I haven't seen any literature about this yet. There have been a few small studies that have just generally shown that a ketogenic diet might be beneficial for people with inflammatory bowel disease, very small preliminary studies. Some anecdotal experiences suggest that some people with IBS or with IBD do well on a ketogenic diet, suggesting that perhaps it is helping the gut barrier, but no one's looked at it mechanistically and I'd love to do that study in the future. 

Christopher:    Yeah. I have a feeling that -- I reached out randomly to Justin Sonnenburg and he said that he was working on a study with Christopher Gardner at Stanford. They just said that they would be looking into the ketogenic diet with respect to changes in the gut microbiota, but I have no idea exactly what they're doing, so maybe we'll get answers in the future. What do you make of it then? I'm sure you listen to podcasts and you read a lot of content online and maybe you've even seen some people speak here at AHS. What do you make of this whole carnivore thing where we're eating tons of protein, tons of fat? There's really no fermentable substrate although you might argue that the connective tissue in an animal is a fermentable substrate. What do you make of that? Do you think it's possible for a human to thrive on that diet?

Lucy:    I think it's possible, but I don't necessarily know that it's optimal. From what I've seen, it seems as though people who have the need to go full carnivore typically have some kind of underlying gut pathology that they've not addressed. It's typically often they're having some kind of carbohydrate malabsorption or intolerance and they feel better getting rid of all that fiber. It's essentially like an elimination diet. Most protein is absorbed higher up in the gut, so it's almost like an elemental diet in a way, but I have a hard time believing that that's optimal for health. Like I presented at AHS today, I don't think that a well-crafted ketogenic diet is necessarily bad for the gut microbiota. I don't think we have evidence for that.

Christopher:    No, I know. I must admit that does annoy me when people -- I was actually at the Real Food Rocks Festival recently in the UK and somebody said that. It was actually Michael Mosley who's a celebrity doctor in the UK and he was talking about the importance of the microbiota, and then this woman said, "What about this keto diet? That's working really well for me" as if the two were mutually exclusive. I've eaten a ketogenic diet for two years where if you looked at my plate, it was mostly covered in plants. It was a high fat diet. It makes you want to break it down and look at the macronutrient content. You would see there's a lot of fat there, but yeah, there are still a lot of plants there too. I don't see the two things as mutually exclusive. 

Lucy:    Yeah, absolutely. I think there's a way to do a ketogenic diet that's terrible for gut health and I think there's a way to do it -- 

Christopher:    Yeah, whipped cream. 

Lucy:    Yeah, and I think there's a way to do it that it could definitely benefit gut health. Plenty of non-starchy vegetables -- I know Robb Wolf has talked about trying to eat your way out of ketosis with non-starchy vegetables and I think that's probably the best way to do a ketogenic diet, is to make sure you have all those because then you're essentially still providing some substrate for those butyrate producers even if they drop to lower levels and you're relying more on that beta-hydroxybutyrate to supply your colonic energy. I still think it's beneficial in general just to have that metabolic flexibility, so yeah, going pure carnivore, you might survive, but you're probably losing some of that metabolic flexibility both in your human cells and in your gut microbiome. 

Christopher:    Yeah, that's a really good point. I've not thought about that. What do you make of all this, the bile acid resistant or maybe even eating bacteria? None of them seem to be good, right? There's a bunch of hydrogen sulfide-producing bacteria that seem to thrive in this high bile acid environment. What do you make of all that?

Lucy:    It's a particularly interesting area and I think we have a lack of research in that area because we've seen that ketogenic diet definitely changes the gut microbiota, definitely seems to increase the amount of bile-tolerant organisms, some of which can produce things like hydrogen sulfide. That may be an issue for some people and that may be why some people don't do well on a ketogenic diet, is perhaps their microbiome responds in a way that's more detrimental, but in terms of overall, I think it becomes a problem when we zero in on one or two microbes and how those are changing because really it's a complex network of interaction --

Christopher:    Right. It's an ecosystem. 

Lucy:    Right, it's an ecosystem and looking at all of the parts doesn't really tell us what's going on at the whole.

[0:25:01]

    I think we need more studies with how the gut microbiota is changing with the ketogenic diet and what potential implications that might have, potentially even doing transplants into germ-free mice where we can really explore the mechanism and potentially see is there any increase risk of cancer, for example, with transplanting that gut microbiota or that type of thing, or are there actually benefits. As some studies have shown, there's at least one study that transplanted the microbiota of mice that had been on a ketogenic diet into germ-free mice and they were protected against multiple sclerosis, for example. That was mediated through the ketogenic diet changes in the gut microbiota and some of the different metabolites that they're producing. It's definitely an evolving space and I think we'll learn a lot more. 

Christopher:    Yeah. I think that the ecosystem thinking is important and I think intuitively, people know this. If you do something to your garden, if you clear a bunch of bad soil, something is going to take that space. You've made a change and you don't really know what's going to come in and replace the missing microbe, the missing plant in that ecosystem. Would you agree with me that the garden analogy is a sound one?

Lucy:    Yes, although I don't think that it's ever really an empty space unless you've taken antibiotics or -- 

Christopher:    Well, that's what I was going to say. Have you ever seen someone's uBiome result directly after they've taken rifaximin? It's like scorched earth. There's literally nothing -- we had a client do it. He had a problem. His proteobacteria was over 10% and then after rifaximin, it was all bacteroidetes. The diversity was down in the uBiome data set, which you might argue is worth looking at that because they've surely collected hundreds of thousands of samples by now. You see the first or second percentile for diversity and it's just only one phyla. Everything is gone. Yeah, you can't argue that rifaximin doesn't do anything. It definitely does. My question is what happens after that? You've just cleared all of this free space inside of this ecosystem. What the hell is going to come back and take it? You really have no idea. You've no control over that, right?

Lucy:    Right. That's something that we really need more research on, is what do we do in that instance. I think there are a couple of interesting, emerging potential therapies that could be beneficial. One is to do an autologous fecal transplant, so if you know you're going to have to take antibiotics, for example, prophylactically for surgery -- what did you say?

Christopher:    I was joking earlier. My daughter, she's nearly six years old now. She's never had antibiotics, so I was thinking maybe I could start a little side business where I'm selling her poop on eBay. Really genuinely, I should probably bag some of it just in case. 

Lucy:    Yeah, but I think in the future, it's possible that we'll store our samples and be able to reinoculate it after antibiotics. At least one or two studies have shown now that that essentially restores the ecosystem within a day of stopping antibiotics, so that's definitely one kind of area for the future that we'll be able to combat the potential negative effects of antibiotics and prevent that dysbiosis that occurs. 

    I'm also really interested in studying how taking butyrate during and after antibiotics or potentially even a Ketone Ester could potentially prevent the epithelial energy starvation and prevent oxygen leakage which then may lead to dysbiosis.

Christopher:    That's really interesting. This morning, I was interviewing Mike T. Nelson and he was talking about compounds that might rescue energy metabolism in traumatic brain injury and you're basically saying the same thing, rescue energy metabolism in this cell after an insult. It's almost the same thing.

    Talk about FMT then. It's rapidly becoming or will become the standard of care for the treatment of C. diff, but it would appear on closer inspection that there's almost nothing that won't fix C. diff apart from the standard of care, apart from vancomycin as the only thing that won't. Probiotics would do it. Autologous FMT will do it. You've already got the C. diff infection. Putting your own poop back in will get rid of the C. diff. I'm pretty sure I can cite a study where that was the case. Other than C. diff, do you think there's going to be any other indications for FMT? 

Lucy:    Absolutely. I think it's an emerging space and more and more research is being done in that area. It seems to work really well for C. diff, but there are few other conditions where we found that it works really well for all people from all donors. 

Christopher:    Well, like I say, it seems that C. diff is so easy. It's not surprising that it works because there's almost nothing that doesn't work apart from the standard of care. Well, we've seen in our clinic either looking for the toxins produced by the virulence factors or we've seen some metabolites on a urine organic acids test and high dose probiotics would do it quite nicely, right?

[0:30:08]

Lucy:    Okay. In that case, you have the C. diff toxins, but you don't actually have pseudomembranous colitis from the C. diff, so I feel that that's very different. In the case where you have someone who's got an advanced infection then only a fecal transplant was going to work. Probiotics are not going to help you once you're past that, but yeah, if someone has very low levels of C. diff --

Christopher:    Yeah, of course. We're always talking subclinical. We're running a coaching business with athletes. We're not talking about immunocompromised patients in an acute way of setting. 

Lucy:    Yes.

Christopher:    Talk about the logistics of FMT. Places like the Taymount Clinic have become increasingly popular, but you don't have to poke around too much online to find very large question marks over the quality of the donors and perhaps some potential limitations of their procedures. Would you ever send someone to the Taymount Clinic?

Lucy:    To be honest, I haven't looked into different FMT clinics too much. It's something I definitely want to research more. I guess currently, I would just really stress that it's really important to have extensive donor screening. There was actually a recent FDA report that came out that -- 

Christopher:    Yeah, I saw that. Somebody died.

Lucy:    Yeah, somebody died and another person contracted a severe infection because the FMT contained multidrug-resistant organism. 

Christopher:    Right, but again, we're talking about severely immunocompromised -- my understanding was that was not somebody at home trying to fix that IBS. That was somebody's hospital.

Lucy:    Sure, but I still stress that there's a lot we don't know in terms of our screening techniques right now and I would encourage people not to try to do FMT at home and to find an experienced clinic to do it with. 

Christopher:    One of the reasons we've continued to do the traditional stool culture like the one that's available via Doctor's Data is -- Tommy has said, "Well, the traditional stool culture is the gold standard of microbiology. You can tinker around with this PCR nonsense if you like, but as far as I'm concerned, the traditional stool culture is the gold standard." Is that sentiment just wrong? Is it just out-of-date? What's going on there?

Lucy:    I think it's just outdated. I think the gold standard now is PCR whether it's labeled that or not. I think sequence-based testing is more accurate. You can argue the case for parasite detection because they seem to be fairly comparable in the specificity and sensitivity, but in terms of identifying bacteria in the human gut, culture is terrible. 

Christopher:    Okay. Talk about that. Talk about what a culture is, how it differs from PCR and why it's terrible.

Lucy:    Culture essentially, when you do a culture-based stool test, you're essentially taking the fecal sample and you've got this culture media that you think supports the growth of a fair amount of microbes, but the microbes in the human gut thrive in an anaerobic environment, no oxygen, so it's actually very hard to culture most of the organisms that live in the human gut. I've done a number of independent tests where I've sent the same stool sample to culture and PCR and 16S Company and I've shown that the amount detected, the total abundance of bacteria that were detected via the culture-based stool test is only equivalent to less than 4% of what's detected with the 16S.

Christopher:    Right, which is not surprising given what you know about the way it works. 

Lucy:    Right. Essentially, we have a culture that's selecting for very rapidly growing microbes that tend to thrive in a particular culture media that is chosen, and even if you do, I think Doctor's Data uses about five different culture medias to try and improve that. There's still only 45% of the total ecosystem. What does that really tell you? The other thing is sometimes you'll have a pathogen that comes back on there that's four plus growth in culture and that's the maximum growth in culture on their semi-quantitative scale. If you look at what that is in the same sample that you run by 16S, it could be less than 0.01% of the ecosystem, but it tends to just grow really well in that culture and that's particularly true of the facultative aerobes.

Christopher:    So is the whole test, is the whole Doctor's Data test useless or can I just get that top section and rip it off, throw that in the bin because there's some other stuff lower down on that result. 

Lucy:    Yes, exactly. It's clear that the bacteriology, that first top section, you could just rip off and throw away. The yeast is questionable. I haven't done enough comparison tests where yeast has shown up to be able to tease out how the yeast connotation on the culture compares to yeast on a GI-MAP for example, but the latter pages, the parasite testing, digestive health markers, inflammatory markers, I think all of those are still very useful, so Doctor's Data could still be useful especially if you have someone who's got some ongoing gut inflammation or you suspect that they have some kind of macronutrient malabsorption, that kind of thing. 

[0:35:10]

Christopher:    Yeah. It's interesting, isn't it, because it is a CLIA-approved laboratory, so it's a legit clinical test. Why don't the CLIA step in and say, "You know what? This stool culture thing is nonsense. Can you stop doing it please?"

Lucy:    At least my understanding is that CLIA, it only suggests that you can reproduce the same result. If you have good reproducibility, even if it's no longer gold standard, you can still potentially have it out there. To be honest, even most conventional clinics aren't using 16S or they're not looking deeper into microbiome testing, and so I don't think there's been that shift yet in clinical practice. I think that's why there are still some companies that are using culture. 

Christopher:    You like the Diagnostic Solutions' GI-MAP as we do. Is there anything on there that I can just tear off and pop in the bin? They keep adding stuff to that so quickly. It makes me very suspicious. They also keep changing the reference ranges like the anti-gliadin IgA, I saw that reference range every week for ages. Again, I've not had that much transparency. I get glimmers of contact with the technical support people, but they're not as successful as I am with the blood chemistry calculator, not even close. Is the whole test good or are there just particular parts that you're interested in?

Lucy:    I definitely see a lot of benefits in the parasites, yeast, bacteria. Some of the other markers, it's hard to determine. I'll say that for example, zonulin is an add-on to the GI-MAP.

Christopher:    Yeah. I don't normally use that.

Lucy:    You generally use that?

Christopher:    I don't.

Lucy:    Oh, you don't.

Christopher:    I've never had, not for a really good reason though, I have to say. 

Lucy:    Studies have shown that zonulin even fluctuates over the course of the day.

Christopher:    Oh, okay. 

Lucy:    So the question is does it really reflect gut permeability? I'm not going to say any test is perfect, but I think based on the analyses that I've done, comparing these different stool tests right now, I'm finding that GI-MAP is the most helpful. Also, it's often within my client's budget in terms of what's accessible, to get even more granular, you'd have to go to Metagenomics. There are a number of companies emerging in that space and I'm constantly looking at what's coming out, what other companies are coming up, and evaluating those because I think soon, Metagenomics will drop in cost so much that we'll want to move to Metagenomics because essentially you can tell more about microfunction. Basically, you're sequencing every gene in the sample, every microbial gene. From that, you're getting a whole lot more information about species, strain, function. Right now, it's just not feasible to run Metagenomics repeat testing. 

Christopher:    Right. It's only really done in a research setting. 

Lucy:    Correct.

Christopher:    Okay. Just to make it clear, we talked about Doctor's Data, which is the traditional stool culture, and then we talked about the Diagnostic Solutions' GI-MAP, which is a PCR DNA test, so it's a very different methodology. The other technology -- what did you say again?

Lucy:    Metagenomics.

Christopher:    Yeah. I've not even seen a commercially available test -- 

Lucy:    There's a few that have emerged. Onegevity is one that I've been looking at. Sun Genomics is another. I'm currently exploring these different ones to see if they'd have clinical utility and speaking with some representatives from the companies. There's also another one that's emerged, Metagenomics's DayTwo, but they're specifically looking at using Metagenomics to predict blood glucose response. 

Christopher:    Yeah, you're right. I have seen that study. I know what you're talking about. What do you think about SIBO breath testing? She's laughing, but I've been around for long enough now. Bryan Walsh, a naturopathic doctor friend, talks about this a lot. Things come and go so quickly. MTHFR was all the rage in 2014. Now, we're laughing at people for worrying about MTHFR. Bryan has seen so many things and he says the same thing about SIBO. Ten years ago, nobody even knew what it was and now, you're negligent if you don't do the test, and we have used it in our practice. We've run a bunch of the SIBO breath tests and they quite often don't correlate with people's symptoms whatsoever. Do you think they have clinical utility?

Lucy:    Yeah.

Christopher:    Pimentel was a legit researcher that's not far from here. We're in San Diego. I think he's in LA somewhere, but he's obviously the real deal and he's advocating these tests both at his research and his clinical practice, I think, so surely they are the real deal. 

Lucy:    I've actually written about this extensively on my blog.

Christopher:    Oh, really? I apologize.

Lucy:    No, it's great. I do not believe that SIBO breath testing has clinical utility. I think there've been enough studies to question the reproducibility of it, the fact that with most test results, when you actually -- they've done studies where they've administered the carbohydrate bolus that you take. 

[0:40:03]

Christopher:    And it depends. There are all these nuances. Is it glucose? Is it lactulose? 

Lucy:    Yes, but it's also when you radio label that substrate so you can actually see where -- you can track where it is in the gut. Most cases, it's in the large intestine before 90 minutes and you're seeing fermentation. That's normal from the colon. I used to do some breath testing with my clients until I saw this research and really dug into it and completely shifted my paradigm in terms of whether it's useful. I think in general, the other thing to mention is that SIBO tests for all of Dr. Pimentel's research -- and I have to credit him. He was essential in bringing bacteria to light as the cause of irritable bower syndrome. 

Christopher:    Yeah, gastroenterology, yeah, exactly. That's a really good point that you should make. When I went to see a gastroenterologist, they were not interested in the microbiota or the microbiome or whatever you want to call it. They didn't even think it was anything to do with what I was eating. They just wanted to use scopes to confirm why I had already said and then they wanted to start suppressing things with steroid anti-inflammatories and when they stopped, that stopped working and they wanted to start cutting bits out. Yeah, Pimentel has brought that community on leaps and bounds, I'm sure. 

Lucy:    Yes, absolutely, but the problem is that SIBO breath testing has been validated based on culture. 

Christopher:    Oh shit. That's a problem. Your grand truth was a little bit shaky.

Lucy:    Yeah. Essentially, what we think has been -- we've basically said that patients have bacterial overgrowth when we put and aspirate from the small intestine in a Petri dish and it tends to have a lot of colony-forming units. So we're quantifying the amount that's in culture and saying you have bacterial overgrowth because you're over this threshold of culture. What we're actually seeing is that it seems to be individuals who have high proteobacteria in the small intestine. When you culture that bacteria, it tends to grow a lot. Recent research from Dr. Pimentel has shown that when you have SIBO by the culture-based diagnosis, you have high proteobacteria. They've shown it in the direction of if you have SIBO, you have high proteobacteria, but in reality, if you have high proteobacteria, your bacteria grow well in culture.

    The most recent research that just came out in March which I wrote about quite a bit is that it's not actually necessarily bacterial overgrowth. It's actually small intestinal dysbiosis that is correlating with the symptoms we typically think of as the SIBO and IBS. 

Christopher:    Okay. That's really interesting and it's not necessarily the case that you could find this proteobacteria on a uBiome test although you will see proteobacteria on a uBiome result. It's looking at the colonic bacteria, not necessarily what's going on in the small intestine, right?

Lucy:    Correct. Well, actually, there are differences between the colonic microbiota and even the fecal microbiota. There are even some differences there. Fecal, colonic, and small intestinal will all be different in terms of their composition. Even the fecal microbiome is not necessarily directly representative of the colonic environment, but that being said, most studies to date of humans are on the fecal microbiome. Most of what we know to compare to is studies that have used fecal microbiome in terms of how interventions affect it, how antibiotics affect the gut microbiome. It's mostly been on fecal samples, so I still feel like fecal samples are useful, but they don't necessarily tell you anything about the small intestine.

Christopher:    Right. Okay. Is there anything else clinically useful you can glean from a uBiome test? I have to make it clear actually that in no way do uBiome advocate the $99 Explorer test as a clinical test. It's not CLIA-approved as a clinical test as far as I know. They do offer some clinically-approved tests, which have been in trouble -- I'm sure you've been following the hoo-ha with the SmartGut test and all of that. I'm talking about the Explorer test, the $99 one, the 16S test. Is there anything else clinically useful that you can glean from that data?

Lucy:    Yeah. My understanding is that the Explorer and the SmartGut, which was their clinical tests, it's the same techniques that they're using. It's just different in how they present the data. 

Christopher:    Marketing really. The Explorer is for the citizen scientist, whatever the hell that is, but it's definitely not for practitioners. I'm sure there's legal and PR reasons why they make that distinction. 

Lucy:    Yeah. In terms of what we can glean from that test, mostly at the moment, I'm using it to look for major red flags, so high proteobacteria is the key one. Sometimes I'll also see Akkermansia muciniphila. It's another really interesting microbe that's in low abundance, around 1% to 3% of the ecosystem. It's associated with better metabolic health, lean BMI --

[0:45:02]

Christopher:    Right. It's a major butyrate producer as well, isn't it?

Lucy:    Not Akkermansia. It's a mucus-associated bacterium. I'm not aware of any butyrate production from them. 

Christopher:    I got that wrong. I'm sorry. What else? Other red flags? Missing bifidobacteria, you already said the [0:45:16] [Indiscernible] don't have it anyway, so maybe that doesn't matter. 

Lucy:    Well, perhaps, but they may have other protective microbes that we don't have anymore. I typically locate what the levels of lactobacillus and bifidobacterium -- I kind of see in general how many butyrate producers are present. I was talking about Akkermansia though. It seems that at low levels, it's very beneficial, but it seems to undergo this massive expansion to up to 20% to 40% of the ecosystem in cases of severe gut inflammation, so that's kind of a red flag. 

Christopher:    So generally, more isn't necessarily better. 

Lucy:    Yeah, exactly, but it seems to reduce the diversity of the rest of the gut microbiota as well when it's expanding that much. It may be an adaptive mechanism to an inflamed gut because they've actually shown that Akkermansia is important in healing mucosal wounds and it actually benefits that process, so it expands about tenfold in the mucosa wound environment and helps with repair. It may be an adaptive mechanism, but it might suggest that really focusing on bringing down inflammation might be particularly important in that particular person, for example. 

Christopher:    Okay. Are there any other species that you're particularly interested in like roseburia or Faecalibacterium prausnitzii? Did I say that right?

Lucy:    Yup. Those are both really important butyrate producers. I would consider those in general with other butyrate producers, but it's interesting that it also seems to be strain-dependent, and of course, the uBiome doesn't get down to the species and strain level.

Christopher:    Right. Is it just that the database just needs the right primers or something? If they had that, they could tell you, or is it just a limitation of the test?

Lucy:    No. It's because of how the methodology is set up essentially. With 16S, they're basically sequencing a conserved region of this gene in the bacterial ribosome. It turns out that this gene, parts of this gene are conserved across all bacterial species, but parts of it are hypervariable. It's the hypervariable regions that are different between different bacteria that allow you to say okay, this sequence here matches up with this bacteria in the database. It just so happens that among a lot of microbes of the same genus, they just have the same sequence for that hypervariable region, and so you can't distinguish. You can't get any more granular just based on that small sequence. That's where metagenomics is the alternative where you're sequencing all the bacterial genes and then you can definitely pinpoint which species and strains are present because you have more sequencing data. 

Christopher:    I'm tempted to now get into what do you do to manipulate the gut microbiota, but I think I might just leave everyone hanging actually because it's just too big. It's a whole another podcast, isn't it? Are you using botanical herbs? Are you using prebiotic powders? Are you using recommendations for diet? Can you give us a broad strokes overview there?

Lucy:    Yeah, sure. To be clear, I do not have any medical degree. I'm mostly discussing the evidence for these various interventions with clients -- 

Christopher:    You're educating and you're informing them. The client makes their own decision about what they're going to buy. 

Lucy:    Hopefully with a consult with their physician. I am big on educating about different prebiotic interventions, probiotics, especially the importance of choosing strains carefully, so a lot of people don't recognize that there's great strain specificity. 

Christopher:    Yeah. Actually, the interview with Jason Hawrelak, we didn't really talk about the Meet Your Microbiome masterclass. We talked about the strain specificity of probiotics. I honestly fell for that one. I didn't even know. You read the studies and it says lactobacillus rhamnosus GG and there are maybe even some numbers after that, and then you'd look at the bottle and you say, "Oh yeah, lactobacillus, it's all good. It's all lactobacillus. That's fine." No, it's not fine. I'll link to that episode so you don't have to repeat all of that. I think people listening now know the applications are strain-specific. The other big take-home from that podcast was that these things are not going to take up residence. It's highly unlikely that you're going to -- even though you can buy bifida bacteria in a probiotic, it's highly unlikely that you're going to put it back using a probiotic. 

Lucy:    Absolutely. I actually went to the International Probiotics Conference in June and there are some researchers who have identified certain strains that they're working on getting to market now that potentially do stay in the gut for a longer period of time in a good number of people. Right now, commercially available probiotics most do not colonize for more than a week to sometimes a couple of months, but typically not more than that. 

Christopher:    Are there any prebiotic powders that you find yourself using on a regular basis? I've been experimenting with -- I don't know if you've tried it, the pomegranate husk powder. Have you tried that?

[0:50:02]

Lucy:    I have not. It's one I want to look into because I heard about that through Jason Hawrelak.

Christopher:    Yeah. It's got ton of references. It seems to be the Holy Grail where it's antimicrobial to the stuff you don't want and it's a prebiotic to the things that you do want. 

Lucy:    Correct. I would love to see a clinical trial with that in terms of the gut microbiome. 

Christopher:    I've not looked at all the studies, but I'm sure there's a bunch of culture stuff in there, right?

Lucy:    Yeah, exactly. Well, the thing is in that case, they're taking in anaerobic culture and they're inoculating it with the whole human fecal sample, so in general, you're getting potentially a more representative ecosystem than you would with a culture plate. However, there's still a lot we don't know about which microbes are being modulated. Jason Hawrelak has done some great research in vitro looking at how these different herbs can impact the gut microbiota, and from the small selection of microbes that he was able to study, it does seem that pomegranate husk inhibits pathogens while stimulating beneficial bacteria, but I'd love to see it done in the entire ecosystem and in the context of a real gut. 

Christopher:    I can tell you what it does in a real gut in vivo. It's epically awful in taste. Have you tasted it?

Lucy:    No.

Christopher:    Oh, it's apocalyptically bad. It's as bad as the ketone ester. It's that bad. It's like this weird hydrophobic powder so if you mix it in water, you can turn it into a solution. Really it's a suspension and then you drink it down and then you burp it back up, and so the awful taste just keeps coming back and back. I could imagine just blowing the powder back up. Oh God, it's terrible, but I've been experimenting with it on myself for a while and it does seem to help me. I tend towards -- IBS is my long clinical history that's largely fixed now, but I definitely tend in that direction still. I've done the engineering thing where I take that, try it, it gets better. I go from okay to great, and then take it out, goes back to okay. 

    I've done that a couple of times now and it's as cheap as dirt. It's a waste product. Nobody eats pomegranate husk, so it's a waste product. I'm just a bit worried about it's difficult to source at the moment. When you look online, you hardly find anyone selling it. I've got it from this weird spice producer. Are they doing mass spec on this stuff? I very much doubt it. Hopefully it doesn't have a bunch of cadmium and goodness knows what else in it. Maybe if the evidence does come to light, I'm sure more supplement companies will move in to start making it. 

Lucy:    Yeah, that'd be great. 

Christopher:    Is there anything else? Partially hydrolyzed guar gum and all these fancy things, glucomannan and all these things that have fancy names, are there any of those you use regularly? I say "use". I'll take that word back. 

Lucy:    I don't use any myself. I mostly focus on dietary sources of fiber mostly because I think it's more beneficial to get them in the context of a whole food than in isolated form. 

Christopher:    Yeah, of course. 

Lucy:    I do think there's a lot of interest and rightfully so in prebiotic supplements. What's most interesting to me is I've heard at several recent conferences people who have done studies where they show that essentially prebiotic response is highly individualized. Your response to prebiotic may be very different than mine because of the differences in our baseline gut microbiota. They've even shown that for example, resistant starch we know is supposed to increase butyrate, right? On average, it does, but in some individuals, they actually go down in butyrate production with the resistant starch maybe because it's causing inflammation. We just don't know. It's interesting. There are actually companies now that are looking to do -- 

Christopher:    Sequencing and then sell you a supplement. 

Lucy:    Well, yeah, essentially take your fecal sample and put it in a 96-well plate with a whole bunch of different prebiotics, test how much butyrate is produced in each well, and then they could essentially see what prebiotic would boost your butyrate production the most, for example. They're currently doing studies where they're comparing what in vitro diagnostic results they get and see how well it correlates with response in vivo. 

Christopher:    All this stuff is right for supervised machine learning, right? The ground truth is the culture. I do that a bunch of times. I might even need to do that 2000 times and that might be a big enough data set to where you can just send me your uBiome data and I'll predict which prebiotic is going to have the greatest impact in terms of butyrate production. 

Lucy:    Yeah. I think personalized microbiome medicine is the future and I think we'll see a lot more machine learning and AI getting involved in that and in predicting which interventions might be most beneficial based on your baseline gut microbiota. 

Christopher:    Yeah, awesome. Well, what question should I have asked? Is there something that I should've asked you and I didn't?

Lucy:    I've done a lot of research actually on exercise in the microbiome, so that was actually what my dissertation research was on, was studying the effects somewhat of fiber, but we've also just generally looked at the effects of exercise training independent of diet on the gut microbiome and found some really interesting results. For example, we took sedentary individuals, put them through a six-week aerobic exercise training intervention and found that it increased fecal butyrate and butyrate producers especially in our lean individuals, so that was particularly interesting. 

[0:55:09]

Christopher:    That's also good, right?

Lucy:    Yeah. 

Christopher:    Okay. Are there any other key findings?

Lucy:    We did another interesting study. We've shown that actually strenuous exercise in mice tends to exacerbate colitis versus voluntary wheel running. If you just give the mice a wheel and allow them to run as much as they want throughout the day, it actually attenuates colitis. The two different modalities actually produce different shifts in the gut microbiome. We actually did the transplant study where we took mice that were sedentary or mice that had run on a wheel for six weeks and transplanted those gut microbiotas into germ-free mice, who've seen no microbes in their life so we could determine is the microbiota actually what's protecting against the colitis. We found that the mice that received the exercised microbiota, even though they never exercise themselves were more protected against the colitis than the mice who received the sedentary microbiota transplant, so that was pretty wild to us, suggesting that the changes that exercise is inducing in the gut microbiota are protective for gut health. 

Christopher:    Okay, but only a certain -- I guess any triathlete can tell you this that if they just go out for a mellow run then maybe their gut health improves. It might even help them go like if you've got a bit constipated, that might help modulate things a little bit, but if you're doing a race -- have you ever seen the line for the porta potty at triathlons? Is it the same thing that you just found in mice?

Lucy:    Perhaps. 

Christopher:    This is stress. Immunity and digestion are long-term building projects. It doesn't make sense to invest in those if you're currently being chased by a tiger, so you turn off the immune system, turn of digestion, and then what you're seeing is the shift, the appropriate or the according shift in the microbiota. 

Lucy:    Right. There's some interesting research that is now being done on the microbiome of marathoners, and in particular, what dietary strategies might be best for mitigating some of those adverse symptoms that occur during high performance exercise.

Christopher:    What did you make of -- I'm sure you saw it -- Lauren Petersen's work in elite cyclists where she showed I think a causal relationship in some particular species and exercise performance --

Lucy:    Veillonella?

Christopher:    I couldn't remember the name of the bacteria, but it's generally regarded as not very good and it does raise interesting questions like is this a hormetic stressor? Is it somehow affecting carbohydrate metabolism? What did you make of all that? It's a particular interest to our listeners who are mostly athletic. 

Lucy:    Right. I had some issues with the methodology of that research. 

Christopher:    Oh, really? Oh, you scientists, you always have issues with the methodology. 

Lucy:    Well, I think it's really interesting that they're studying that population. I think they just got a little bit too focused on that one particular microbe and it did seem to be very variable. If you actually look at the supplementary data, only about half the marathoners actually had an increase in that microbe, so it wasn't the same across the board. I didn't see any GI symptom questionnaires either, so we don't actually know. Maybe those individuals -- veillonella feeds on lactate and they show that lactate was leaking into the lumen, but perhaps it's the athletes with the leakiest guts that are getting more lactate into the lumen and potentially having this expansion of lactate post exercise. 

Christopher:    Oh, very interesting. 

Lucy:    They did transplant veillonella or provide it to mice essentially as a probiotic to see if it would enhance their exercise performance. To be honest, the difference in their exercise performance was highly variable even among the genetically identical mice and was not much of a boost in performance anyway. I think it's an interesting story and I'd love to see that explored more, but I'm not convinced quite yet. I'm pretty sure they're trying to start a company providing veillonella as a probiotic supplement, which I'm very concerned about given the lack of other research on it. 

Christopher:    That's interesting. I would've thought that subjective questioning in athlete gut symptoms is absolutely critical because we've worked with thousands of them now and I'm not sure exactly what's going on, but it might be that there's just a readjustment of what normal is. People think that diarrhea every now and again once or twice a week is normal, and Tommy and others have argued, "No, that's not normal." I think subjective questioning is something that's absolutely mandatory with an athletic population, probably any population. It's not that hard to collect that. It surely is easier than collecting poop. Why not just send a survey out? It makes sense to me. I don't know. I should be quiet because I've never tried to organize a clinical trial. There are probably a lot of people listening to this that have that would object to that.

[1:00:00]

    Well, this has been wonderful, Lucy. Thank you so much. I very much appreciate you. Is there a way that people can work with you right now? Can I pay for your time and get you to look at my uBiome data and then you educate me on what the scientific literature says and then I can go away and discuss that with my doctor and make a decision?

Lucy:    Sure. I do work with clients one-on-one. I currently have a pretty long wait list, but you can find that on my website. Also, I have a whole list of resources about what we've talked about today testing microbiome modulation at www.ngmedicine.com, so NextGen Medicine, ngmedicine.com. People can potentially sign up to work with me there. 

Christopher:    What the hell is going to happen when you go to medical school with that enormous long line? It's going to get longer, isn't it? What's the solution to that?

Lucy:    Well, I'm working on potentially creating a course --

Christopher:    Oh, that'd be great. 

Lucy:    -- this year to provide an evidence base so people can self-empower to see where the evidence is and hopefully improve their gut health that way without having to see me one-on-one because I know that my time is going to get even more taken up the next couple of years at med school. 

Christopher:    Yeah, it's crucial. I'm sure there's a lot of repetition in your one-on-one work and for you as a practitioner, not burning out is important too. If you can get people -- maybe even mandate it. I know that Josh Turknett, our neurologist, he has a migraine training course and he insists -- so in general, online training courses have terrible completion rates like 2% or 3% is very typical. Sometimes, 10% of people just starting it is quite normal. So what Josh does is he mandates that people do the training course before they speak to him one-on-one and he says nine times out of ten, by the time they've done the training course, the question has been answered, so they don't need to talk to him. I'm wondering whether that might be the same with you --

Lucy:    Yeah, I love that model. I just finished my PhD. I'm taking a gap year to work on this course and a couple of other passion projects before starting med school next August, so I'm hoping to roll out that course and have that be a source for people when I can't work with clients one-on-one. I have a couple of other things coming out that I'll be excited to share too. 

Christopher:    Oh, good. Good. Maybe I can have you back on. I'll certainly be happy to do the training course and promote it in any way I can. 

Lucy:    That'd be great. Thanks!

Christopher:    Thank you so much. I appreciate it. 

Lucy:    Thank you.

[1:02:26]    End of Audio

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