The State of the Research: Gut Health Interventions

Hello and welcome to The Perfect Stool: Understanding and Healing the Gut Microbiome. This is your host, Lindsey Parsons, and today on the show I have Lucy Meiling, who recently finished her PhD at the University of Illinois in nutritional sciences, focusing on how diet and exercise impact the gut microbiome. And she has authored several peer-reviewed journal articles related to the microbiome and Health and was named an emerging leader in nutritional sciences by the American Society for Nutrition in 2017. And Lucy also served as a staff research associate for the Kresser Institute for Functional and Evolutionary Medicine since 2015. And she's the founder of Next Gen Medicine, writing evidence-based articles about gut and skin health, nutrition and the microbiome, exercise science, and colonocyte metabolism and the oxygen-gut dysbiosis connection, which we're going to talk about today. So let's get right on to the show. Welcome to the podcast, Lucy, and thanks so much for coming on.

Thanks so much for having me, Lindsey.

So I'm wondering where you're calling from today, because I know you were taking a few months to travel around Australia, New Zealand, and Japan after finishing your PhD.

Yeah, today I'm calling from San Diego.

Oh, okay. Nothing exciting, but well, sort of exciting.

Definitely more exciting than the Midwest this time of year, which is where I'm from.

So, oh yeah, well, I'm in Arizona, so also thankfully in a warm climate.

Mm-hmm.

So what, where was it? What was your favorite of all the places you visited?

Oh, that's really hard to say. The Great Barrier Reef was particularly spectacular. So that area of Australia was really quite amazing.

Yeah. Did you go snorkeling or scuba diving?

Yeah, we did. We did both actually. It was our first time scuba diving. We did a kind of a combined snorkel and scuba tour.

And what was the best thing you saw?

I can't say we saw anything, you know, that's going to blow anyone out of the water, but lots of clownfish and sea turtles. You know, it was just really cool to see, see everything so diverse down there.

Yeah. Well, we lived in Australia for a few years and got to visit the Great Barrier Reef several times. So yeah, it's awesome.

Yeah.

So before we get to our primary topic for today, I wanted to at least throw a nod towards your PhD research and ask about the impact of exercise on the gut microbiome.

Yeah, sure. That's a, that's a great place to start. Yeah. So really the lab I was in was really interesting. They were just getting into the microbiome shortly before I joined the lab. And it was really because they had started to do some trials looking at whether exercise could be beneficial in models of colitis or inflammatory bowel disease. And they were finding these kind of really interesting results where voluntary wheel running if you, if you allowed mice to run on a wheel as much as they wanted, it was protective against colitis.

Interesting.

Whereas if you forced them to run on a treadmill once a day, it actually exacerbated the colitis and increased mortality. And so they were seeing those disparate results and wondering, well, maybe, maybe it's having different effects on the microbiome. And sure enough, fellow lab member, past lab member of mine, Jacob Allen, did some studies and found that there were different effects on the microbiome depending on which type of exercise the mice were put through.

Because of how much they liked it or because—

Potentially, yeah. I mean, the forced treadmill running is very stressful to them. It's also an acute single bout once a day. Whereas when you provide them with a wheel, 24-hour access to a wheel, they kind of jump on and off all day and do it, you know, as they please. So it's definitely a lot less stressful to them. They like to do it. Actually, if you put a wheel out in the wild, You can capture wild mice will jump on it and run. So they really do like to do it intrinsically. So yeah, it might be a question of whether it's the motivation and how stressful it is, but that was really how our lab at the University of Illinois got into microbiome work was really seeing that it was the impact of these different modalities on colitis and then on the microbiome. And of course we wondered if it was a causal relationship. So we actually then did a study where we transplanted the microbiome of mice that had exercised into, uh, what's called germ-free mice. So those are mice that are raised in kind of a sterile bubble for the entire beginning of their lives. And it can be used as a model because then we can transplant in microbiomes that have received different treatments and see if the differences in the microbiome confer effects on physiology.. And indeed, we found that when we transplanted in an exercised microbiome into these germ-free mice and then gave them a chemical that's, that's known to induce colitis, it was the exercised microbiome was actually protective against colitis, despite the fact that these mice never actually exercised themselves. So that was showing to us that the exercise does have beneficial effects on the gut microbiome, and those effects are protective against disease.

And were you able to drill down to the nature of the effects at the bacteria level?

Yeah, not yet. That's definitely a, a future direction.

Mm-hmm.

For the lab is to kind of try and tease out which bacteria might've been responsible for that. We do have a hunch that it might be the fact that exercise tends to increase butyrate-producing bacteria. And we'll probably talk about butyrate quite a bit.

Yeah.

Today. But you know, butyrate's that bacterial metabolite that's really important for supporting the health of the gut barrier. And, and, you know, of course gut barrier function is really important in colitis. So we think that might be part of the mechanism, but there's also, you know, a lot of things that go on when, with exercise and a lot of different changes that are going on in the microbiome.

Right. And just, just in case anybody doesn't know what a metabolite is.

Oh yeah. So that's something that basically a compound that's produced by microbes, kind of an often an end product of their metabolism. So for example, microbes will ferment fiber and the metabolite that they produce from that fermentation of fiber are short-chain fatty acids like butyrate. Okay. For example.

Great. So was there any, any studies in the human realm that looked at colitis in particular?

Yeah, so we actually have not looked at colitis yet. We ongoing studies, I, I've graduated now, but ongoing studies in the lab are hoping to do a human trial of patients with ulcerative colitis and put them through a 6-week exercise training program to see if it can have benefits on colitis. We did during my PhD work, uh, one of my major projects was the first longitudinal human study of exercise on the microbiome. That was actually in healthy volunteers though. Um, so we had a lean and an obese group, but otherwise metabolically healthy and, and put them through a 6-week aerobic exercise training intervention. And we did in fact show that the microbiome changed during that 6 weeks, including seeing an increase in butyrate-producing microbes. And then when the participants went back to their sedentary lifestyles, a lot of those changes again reversed back to baseline.

And how long did it take for that change to take place? Did you track them in between or did you go for 6 weeks and then test?

Yeah, we had a, we had one interim sample at 3 weeks and at the 3-week analysis kind of revealed that some of the changes had occurred, but it wasn't as full as the changes at 6 weeks. So it'll be interesting to do future studies that look at— do increasing serial samples and, and see, uh, you know, what, what the minimum effective dose is.

Yeah. And was it cardio-type exercise or was there intervals or anything else involved?

Yeah, so this was a— it was completely aerobic training. So it was 30, 30 to 60 minutes on a treadmill or a bike 3 days a week. So it was— it started off at the first week Um, these were sedentary individuals, so we kind of ramped them up into the training. The first week was 30 minutes at 60% heart rate reserve, so about 60% intensity. And then by week 6, they were doing 60 minutes at 75% heart rate reserve or intensity. So essentially ramped them up into a, a pretty good level of fitness by the end. And we did show that the training intervention increased their cardiorespiratory fitness, which was associated with changes in the microbiome.

And were the micro— did you see that increase in butyrate producers?

We did, especially in the lean folks. Not quite sure why we didn't see as much change in the, in the obese folks, but perhaps in that case, it's possible that diet was having more of an effect on, you know, maintaining the status of the microbiome. And maybe that's why we couldn't see major shifts with exercise, but definitely in the lean folks, we saw a significant change in the butyrate producers. And I should also note that it was a relatively small study, so it's possible that we just didn't have the statistical power to see it in the obese individuals.

Yeah. And did you see a difference in the starting microbiomes in the lean and obese individuals?

Oh, definitely. Yeah.

I mean, okay.

Pretty, pretty similar to what's been shown in the literature before.

Right. So, so it may be that you can only— why exercise seems so ineffective in some people because their base microbiome is not gonna benefit from it.

Yeah. I don't, I don't think we can say that it's not gonna benefit from it. I think it's just, In terms of weight loss, I should say. Sure, potentially in terms of weight loss. But again, this was, this was really only a 6-week intervention and you're not going to see huge changes in body composition in 6 weeks.

Right, right.

Yeah.

No, I, as a health coach, I tell my clients it's about 90% what you're eating and about 10% exercise unless you have the time to be like a professional athlete and literally exercise 5 or 6 hours a day. But you can't exercise off a bad diet.

Right, right.

Yeah. I think that's true. Yeah, so, but if there's that microbiome piece, that's another piece of the puzzle, that's interesting. Mm-hmm. So in terms of diet's impact on the microbiome, I know you're sort of more in the paleo school of thought, and one of the more controversial aspects of the paleo diet is the high red meat content. So I have seen a couple of microbiome studies coming out implicating obviously high red meat consumption or processed meat consumption with colon cancer. But I've seen them now explaining it through the lens of the microbiome. Do you have any thoughts on that?

Yeah, I definitely think there do seem to be some associations there. So when you eat red meat, you do see an increase in certain microbes and those microbes have been linked to colon cancer. But I think we have to be really careful with the microbiome not to zero in on one or two species and try to make inferences from that because it really is a dynamic ecosystem of between 300 to 1,000 different species among different people. And I think if we get too narrowly focused, it's hard to see, hard to know how individual microbes are having an effect there. So I think we need to look at it from more of a network perspective. And I think it's also important, you know, we can zero in on mechanisms, whether it's in the microbiome or not. But if we're not seeing in large-scale, long-term studies that red meat is tied to colon cancer, then I don't think the, the nitty-gritty mechanism matters nearly as much. Right. So there's been plenty of systematic reviews to, to suggest that the effect of red meat on colon cancer is virtually negligible in large-scale, long-term studies.

Good to know since I'm a hearty red meat eater. I hate to say it, but yeah, probably, probably a little less cool environmentally, but, but I've heard some podcasts debunking that as well. So that's a, that's for another time and place. But in any case, I know another, another controversial aspect of paleo diet is the exclusion of legumes, which, you know, most people think of as super healthy foods. So can you talk at all about the impact of legumes on the gut microbiome and their place in a healthy diet?

Sure. I think, I think I was very dogmatically paleo for a long time, partly because it's really what helped me to heal my eczema, and because I did have food sensitivities to a lot of the things that paleo excludes. But I feel like I have a lot— a much more nuanced view of it now. And I think there are people who can benefit from a diet that includes grains and legumes, especially if they're properly prepared. And, and it can have beneficial effects on, on the gut microbiome in terms of of providing a, a source of a number of different fibers that are a little bit more unique to grains and legumes than other foods. So I, I really see it as it kind of depends on where you're at. I think a lot of people with gut inflammation tend to have that exacerbated by grains, legumes, foods that have a higher anti-nutrient content, more lectins. Phytates, those kinds of things. And it might be beneficial for at least a short, short period of time to eliminate those completely to facilitate gut healing with more of a, like a hypoallergenic diet. Uh, but that doesn't mean that if you're healthy and you tolerate grains and legumes well, that they can't be a component of the diet. I just don't necessarily think they should make up the bulk of the diet because they're not the, they're not nearly as nutrient dense, especially if we're considering bioavailability as meat and vegetables.

Okay. So do you think that a vegan diet is a healthy diet for anyone?

That's— I, I don't. I think it's possible to do a vegan diet and cover your nutrient bases, but it's very, very difficult. And I think you need to be— in order to do that, you need to be really knowledgeable and you probably need to supplement to make sure that you're, you're getting the nutrients that you're not going to be able to get from your diet. Uh, so is it possible for someone to do that and thrive? Sure, definitely. Uh, but I certainly don't think it's the optimal healing diet, especially when you are talking about someone who's trying to heal the gut, just because protein and especially bioavailable animal protein is really helpful and crucial to healing the gut barrier.

Okay. So what did you study related to diet and the gut microbiome in your PhD?

Yeah. Most of, most of the studies that we did were looking at dietary fibers and actually we did a number of studies on the gut-brain axis. We had a grant to study that. So primarily my research was focused on exercise for my PhD, although I've certainly, you know, delved into the effects of diet on the microbiome just out of my own interest and through my, my writing on my blog.

And I know there's certainly been a number of voices that have suggested that like a ketogenic diet, for example, might be harmful because it might lead to the extinction of some gut bacteria. What do you think about that and the research behind it?

Yeah, that's, that's really interesting. And I think a lot of people are also against a ketogenic diet because they think that a high-fat diet is bad for the gut microbiota. And the problem with this is that that's really based on animal studies where they're using, you know, when, when you see a high-fat diet in the literature for, for rodent studies, it's really a diet that's high in refined soybean oil, lard, and full of refined sugar and also low in fiber. So it's kind of like the equivalent of like a burger and Coke diet.

For a mouse.

Right. For a mouse. So it's, it's not anything like a carefully crafted healthy ketogenic diet that's based on high-quality meat, fat, and vegetables. So, so I think that's a really important distinction. And the other thing is the natural diet of a mouse is actually low in fat and high in carbohydrates, whereas humans across evolution are able to consume a wide variety of different diets in terms of their macronutrient composition and seem to have this a little bit unique metabolic flexibility in terms of, of what we can consume. So in terms of the ketogenic diet, it's certainly going to produce dramatic shifts in the gut microbiome. And this has been shown in a number of studies. The most well-known was David et al. from 2014, where they showed that if you switch people from a plant-based, high-carbohydrate diet to an animal-based ketogenic diet, it alters the gut microbiota composition drastically within 48 hours. So it's really, really quite rapid shifts. I really don't think there's a lot of evidence that periodic ketosis is going to lead to any loss of diversity in the gut microbiome. And in fact, that may boost gut microbial diversity. There's been some interesting studies, one in particular in the Hadza hunter-gatherers that showed that the seasonality of their eating patterns was what seemed to contribute to the diversity of the gut microbiome is what the authors posited from the results that they got there is that there seemed to be these oscillations in the microbiome depending on what they were eating in the different seasons. And those same microbes that oscillated the most are what's lost, what's been lost in the Western gut microbiome. So it's, it's quite possible that that seasonality or periodic shifts in what we eat could actually facilitate diversity.

Mm. Okay. Interesting. So let's get to the main topic, the oxygen gut dysbiosis theory. So tell me about the theory and the research to date that supports it.

Yeah, great. So I actually came across this, I believe it was last April. So first I saw a talk done by Dr. Sean Colgan at Experimental Biology Conference. And essentially learned that butyrate is essential for the gut barrier. Most people know that, but it actually also helps to maintain hypoxia, or a very low oxygen environment in the gut. So a healthy colon, large intestine, is virtually devoid of oxygen. It's a very low oxygen environment, also known as anaerobic.. And what happens is that anaerobic environment selects for certain healthy bacteria. And what happens when we have gut inflammation is that the epithelial cells, the cells that line the gut, start to become inflamed and they start to leak oxygen into the gut.

Mm-hmm.

And when this happens, a lot of opportunistic pathogens like E. coli, Salmonella, and Pterococcus really like that oxygen and they can use it to outcompete some of the beneficial microbes. So that oxygen leakage is really what is driving the dysbiosis. And in fact, we do see this pattern across different chronic diseases. The most common pattern among all the dysbiosis that's, you know, been observed is that there's this overgrowth of facultative anaerobes, meaning microbes that can use oxygen when it's present. And they do this at the expense of the beneficial microbes, including a lot of those butyrate producers that are so important for maintaining the gut barrier.

And what are some of those species or genera or phyla of beneficial butyrate producers?

Yeah, so there's, there's a number. I can, I can name a few. Lactosporaceae is one. Clostridia, number of different Clostridia produce butyrate. Eubacterium, Roseburia. So there's, there's a number of different genera and families of, of butyrate-producing bacteria. And essentially these are, are crucial to maintaining the health of that gut barrier because if we don't have those butyrate producers, then we're not getting an abundance of of uterine to fuel the epithelial cells and maintain them in a healthy state.

And so what is the, what is the result of that oxygenation and then the increase in, in these facultative anaerobes?

So just generally, the facultative anaerobes tend to be much more inflammatory.

Mm-hmm.

So they tend to stress the gut, cause inflammation, intestinal permeability. And are also directly inflaming the gut epithelium. And what's really interesting is that they'll actually— them inflaming the gut epithelium then leads to more oxygen produced in the gut. So it's almost like these pathogens can hack our gut metabolism to feed themselves the substrates that they need to survive.

And then it becomes a vicious cycle and they, they start to expand.

Right.

And these are all typically from the family Proteobacteria. Or the, uh, most of them.

Yeah, most of them are in the phylum Proteobacteria. That's, that's the most common that's seen. And, and particularly the family Enterobacteraceae is, is the most common to expand in, in this condition of increased oxygen leakage.

Okay. If you're interested in health coaching to start to naturally reverse your autoimmune condition or resolve a gut health issue or lose weight without dieting, I offer free 1-hour breakthrough sessions to talk about what you've been going through and see if health coaching might be the answer. Or I offer a 1-hour functional health and nutrition review related to gut health, autoimmunity, or other health issues if you just need some direction and ideas and a set of recommendations of where to go from where you are. So I'll put both of those links in the show notes, or you can also just go to highdeserthealthcoaching.com and look under work with me. So I had Mahmoud Ghanoum from BIOM, who's a professor at Case who studies the microbiome. So this is from BIOM, B-I-O-H-M. And we did a, we did a biome test for me and he interpreted it on the air and I have 32% proteobacteria. So how screwed am I?

I— so I've seen a couple of results like that on biome that I've compared to other tests and I don't believe the proteobacteria levels on biome. I don't know if it's all of the, all of the bacterial results. That are off or whether it's just the proteobacteria. But I've compared it to companies that are using metagenomics, which is a much higher resolution, higher accuracy way to assess the microbiome. Even though 16S is, is generally fairly accurate, I don't believe the proteobacteria I'm seeing on BIOM. I had, I had another person who had 80% the other day and I just don't think that's physiologically possible.

Okay.

And it wasn't what showed on other tests that I ran side by side. So I'm not quite sure what's going on there, whether, whether it's something with, with Biome's methodology that's, that's skewing the proteobacteria there.

Interesting. Okay. So, so maybe I'm just a little bit screwed, but not totally.

I would say, I would say if you're curious, get it checked using a different test.

So in terms of the 16S, do you have a, or would you just say go, who does the metagenomics tests?

Right now there's a couple. Longevity and SunGenomics are two that I've explored. I'm liking Longevity the best right now because they also allow you to download the raw data and then you can kind of parse through that as well. So that's, that's what I'm using currently. I was using uBiome, which was really great for 16S and, you know, a lot less expensive.

Yeah. Until they disappeared off the face of the earth right after the FBI investigation.

Yeah. So they're, they're totally gone now. Yeah, I know. It's not an option. So I haven't I haven't found another 16S that I feel is reliable, so I've typically recently gone to the metagenomics instead.

And what is the difference between— like, what is that? What are we actually doing in the metagenomics versus the 16S?

Yeah, so the 16S you can kind of think of as like a bacterial fingerprint. So basically what they're doing with 16S is taking a specific gene that is conserved across all bacteria. So it's a part of the bacterial ribosome. It helps bacteria make proteins, essentially. And, and it's conserved enough across all bacteria that they can design primers to sequence just that gene. But there's differences enough between different bacteria that they can also use it to kind of say, oh, well, let's match this up in the database, and this is this bacteria. And so you can kind of match it up and determine down to the genus level which bacteria are which with that, with that just testing that one gene, just sequencing that one gene. The alternative, metagenomics, is taking all of the genes in the sample and sequencing all of them and then matching them back up to databases. So we can get down to the genus, species, and strain level and typically do so with a greater degree of accuracy.

And will Longevity tell you your breakdown of these big phyla? I mean, like, what kind of divisions do they show on their results?

Yeah, Longevity does show the phyla breakdown. They also show your butyrate-producing capacity, which is pretty cool.

Nice.

And they do have a brief pathogen screening profile. I'm hoping that they're going to be expanding that soon.

And do they include fungi?

They do include fungi. Yeah. At least in the raw data. I'm not sure how much they report in the, in the visual reports at the moment. Yeah.

They include parasites or viruses or anything like that?

So they, they will detect them with the metagenomics, whether some of them will pop up on the visualization report that they give you. Some of them you might have to find in the raw data. So for example, things like Blastocystis hominis that are a little bit more is it parasite, is it not, will be in the raw data but wouldn't necessarily show on their— what they choose to report at the moment, at least.

Right.

But I've heard that they may be trying to, to make it a little bit more of a clinical test, and I'm hoping that that happens because I think that right now they're looking like the best in the testing space, but I still, I still think they need some improvements in their reports.

So right now they're geared towards consumers primarily.

Yeah, kind of more, more like uBiome in terms of just people that are interested in their gut health, although they do go as far as to then make recommendations for certain probiotics and certain diets, which I really don't think is— I don't think the science is quite there yet, but a lot of people who are testing are looking for that. So they're, they're trying to cater to that.

Okay, so let's go back to my ridiculous overabundance of— potential overabundance of proteobacteria. And if I look at some of these great anaerobic butyrate producers, and in my reports, I got none of them. So other than doing a fecal transplant, is there any way I can get them back into my system?

Yeah, so the question is, do you actually not have them, or are they just at such low abundance that they weren't detected by 16S? And I would guess since you're, you're relatively healthy and talking to me, my guess is that they're there. They're just not at as high of abundance as they could be, or are maybe even not high enough abundance to be detected with, with 16S, especially if it was skewing with the proteobacteria. Some of the butyrate producers may have also come back lower than they should have.

Mm-hmm. Okay.

But essentially, you know, there's, there's a number of things that you can do to, even if, even if the bacteria have gone down to really low abundance, improving the health of your gut and your diet will essentially help them to refloresce. So the gut really is quite resilient. There's certainly instances where your butyrate producers could go completely extinct, and in that instance, the only way to get them back would be to do a fecal microbiota transplant. But for most people, if you've got low butyrate producers, it is possible to shift the ecosystem back to just allow those to flourish and become more abundant.

And how do you do that?

Yeah, that's, that's the great question, right? So I think the first step is really just to make sure you have the basic health behaviors in place. We can, we can talk about all kinds of advanced gut interventions, but if you don't have the basic, you know, healthy diet, exercise, sleep, and stress management covered, then all the fancy gut treatments, advanced therapies are not, not going to move the needle nearly as much as any of those things. So that's kind of the first step. And honestly, that will shift the microbiome quite a bit back in the right direction.

Any particular aspect of a healthy diet, since obviously so many people define that differently?

Yeah, I think the truth is we don't exactly know what the, you know, what the best diet is for the gut microbiome. And I don't think that there is one best diet for gut microbiome. Everyone's microbiome is different, and, and some people, you know, may respond really well to a ketogenic diet, whereas other people might do better with a diet that includes more plant foods. So I really think it's— generally, I just talk about focusing on whole foods and making sure that you're getting processed foods and refined sugars out of your diet for sure. With— after that, it really is personal experimentation. And if your gut is really inflamed, then it might be beneficial, like I said earlier, to do a short-term hypoallergenic, more hypoallergenic diet like the Autoimmune Protocol to remove some of those more inflammatory foods, at least for a time, to facilitate gut healing. Because healing, bringing down inflammation is going to essentially stop that oxygen leakage, which is driving the dysbiosis.

And what about the role of fiber in there?

Yeah, so fiber can be really beneficial for some people, but for other people, it's just going to exacerbate inflammation. So it's, it's kind of nuanced again, that fiber does seem to be important in some people and is a good way to increase production of butyrate. But you can also— something we haven't really touched on yet is that in a ketogenic diet, even if you're not getting quite as much fiber, you are getting beta-hydroxybutyrate, which is one of the primary ketone bodies produced in the liver, and it can actually feed into the same pathway in the gut that butyrate fulfills. So it can fulfill a lot of the same roles as butyrate. So I, I'm always hesitant to recommend one diet for everyone because I really think it comes down to personal experimentation. And it's, it's really any dietary change is going to shift the gut microbiome. And I don't think we know quite— we don't have the predictive capacity yet to be able to say, okay, well, this is your baseline gut microbiome, this diet is going to be the best and the most healing for, for you.

Any, any thoughts on soluble versus insoluble fiber?

Not really. I, I just generally recommend, you know, if, if you're going with a higher fiber diet, then try to get a mix of both. But, but again, I mean, to be honest, I feel like fiber is kind of this big elephant in the room when it comes to the microbiome, because the dominant paradigm for so long has been that fiber is absolutely essential to a healthy microbiome. And I think we just— we don't know whether that's actually true, especially in humans. You know, we've seen thousands of people now go on the carnivore diet and improve their gut health, or at least reduce gut symptoms in the short term. And that doesn't mean that it's a healthy diet in the long term to completely exclude all fiber. But it's definitely leading us to question and wonder whether fiber is essential in, in all instances. So yeah, I think it's very individual and, and hard to make any conclusions at the moment.

Yeah. And I think obviously when you go on a diet like the ketogenic diet or carnivore, the other big pieces that you're taking out, all of those simple carbohydrates, all of the sugars, all of those harmful things in addition to potentially producing beta hydroxybutyrate.

Definitely.

Yeah. So what if you had this typical overabundance of proteobacteria and oxygen dysbiosis thing going on? What would be the typical symptoms of that?

It really can manifest in a lot of different ways. So we've seen that basically this microbial signature of high proteobacteria and low butyrate producers is found across a wide range of different diseases. So inflammatory bowel disease, irritable bowel syndrome, colorectal cancer, but even like type 2 diabetes, obesity, psoriasis. So it really can manifest in a number of different ways. And it may just depend on your particular genetic predisposition, what manifests for you. And it also may depend on what the rest of your microbiome looks like as to which, which symptoms you end up exhibiting. So it's not really that this, this profile underlies one specific disease. It's kind of a signature that's been— seems to be characteristic of a number of chronic inflammatory diseases.

Okay. So you wouldn't necessarily say, well, people like this typically tend towards diarrhea or less formed stool versus constipation.

No, not necessarily. Although I will say that it's— I see it a lot in my clients that have persistent bloating and abdominal distension. That's a very common one that I see, but it's also probably skewed based on my client population.

Well, that resonates with me. Okay, so talk to me about SIBO and how you think this does or doesn't relate to it. And that diagnosis?

Yeah, that's really interesting. So I've, I've written a lot recently on how we— I think we need a different paradigm for SIBO. And there's been some really interesting research that came out last summer that suggests that it's probably more like small intestinal dysbiosis that underlies the typical symptoms we think of as being bacterial overgrowth. So it's, it's not necessarily that there's too much bacteria, it's that there's is, you know, the wrong balance of bacteria in the small intestine, just the same as we would think about dysbiosis in the colon. And so I think that it's, it's possible that this oxygen leakage is responsible for some of the dysbiosis that we're seeing in the small intestine. So most of the, the switch in colonocyte metabolism and the oxygen leakage so far has mostly been shown in the large intestine. In animal models. And essentially, there are some studies though that point to the fact that this could also happen in the small intestine. So there does seem to be an increased abundance of proteobacteria in people who have the typical symptoms that we've attributed to SIBO. So that's important to consider. And it's also— there have been some studies that, that suggest that a Western, especially a high carbohydrate processed diet, can can lead to some of these shifts in metabolism that in the colon have been associated with that oxygen leakage. So I do think this is probably very relevant for people with symptoms that are more aligned with the small intestine. And, and I'm looking forward to, you know, I'm working with a number of clients that are trying out some of these approaches to try to overcome, overcome the dysbiosis using essentially using this model and trying to repair the health of— bring down inflammation and repair the health of the gut barrier.

So does it matter whether the dysbiosis is in the small or large intestine in terms of dealing with it?

It's a good question. I mean, a lot of the strategies for resolving dysbiosis will be the same regardless of whether it's in the small or large intestine. But the approach might be a little bit different. So for example, cells in the small intestine rely heavily on glutamine, the amino acid glutamine, for their metabolism. And that is what might help prevent oxygen leakage in the small intestine. That's yet to be studied, but I'm hoping that I might be able to, to contribute to research in that area because there's good precedent for the fact that that might be true in the small intestine. Whereas in the large intestine, butyrate or beta-hydroxybutyrate is is the primary fuel for the, for the gut epithelial cells. So we might take a little bit of a different approach. But in terms of, you know, obviously all the diet and lifestyle factors are going to be the same regardless of small intestine versus large intestine. And the truth is, we just, we honestly don't know often whether dysbiosis is in the small intestine or large intestine. You know, people have abdominal distension and pain, and sometimes we can tell based on, you know, how soon their symptoms onset after a meal, if it's quickly after a meal, often that implies it might be something more in the small intestine. If it takes several hours to, to days after a meal, then it potentially more large intestine. If you've got some kind of, you know, if you've got mucosal inflammation going on and it's been identified by a gastroenterologist with an endoscopy, then you can kind of pin down small or large intestine. But in a lot of cases, we just we can't really know exactly where, where it is going on and what's producing symptoms. But the approach is fairly similar for the two.

And so what do you think about these SIBO breath tests?

Yeah, that's, that's been a, a topic I've covered extensively in the last year, and I've really come to change my paradigm around breath testing. It's really become clear to me as I've As I dove into the research in the literature, it became clear that they weren't reproducible enough to, to be sure that you're getting an accurate result. So if it was repeated again a couple of weeks later with no intervention, you wouldn't necessarily get the same result on the breath test. And the second thing was that you weren't really sure when the substrate— because you either usually with a breath test, you take a bolus of glucose or lactulose and then you're testing the breath samples for the next 2 or 3 hours. So, uh, the issue there is you don't exactly know when the substrate gets to the large intestine, right? So when it gets to the large intestine, we expect there to be an increase in the amount of gases that are on the breath. But the problem is we don't know how fast it gets there. And the transit time from, from the, essentially from the mouth to the end of the small intestine it's called orocecal transit time, and that's been shown to vary from as little as 20 minutes to as long as 120 minutes. So unless we're able to somehow track where that is and be able to match it up with the breath test, it really does not have utility in terms of deciding whether someone has overgrowth in the, in the small intestine. So I, I really think that I've moved completely away from breath tests. If someone's already done one, then I will look at it. And sometimes if there's something, you know, if methane is elevated, then it probably indicates that, that something's, something's going on there. But we still, again, don't know if it's small intestine or large intestine with methane.

So what kinds of tests do you like to run on someone who comes to you with say, like IBS symptoms or, yeah, IBD, if they've already— if let's assume they've already addressed diet as much as they can and they're still struggling.

Sure, sure. So typically I would do a stool test and often an organic acids test as well.

Like Longevity?

Onegevity is the stool testing.

Oh, Onegevity?

Yeah, Onegevity.

Oh, okay. I thought it was Longevity.

Onegevity for stool testing and then often an organic acids test. To be honest, I get a lot of complex cases and usually they've run dozens of gut tests. And so often I'm not suggesting that they, that they get any more. But if I, if I had someone who was dealing with IBS-type symptoms, I usually go with a stool test and organic acids.

Okay. And so in your article that you wrote about all this, you suggested that supplemental butyrate might be something that would turn around this state of dysbiosis. Can you talk a little bit about that?

Yeah, definitely. And I should say, I don't think that supplemental butyrate alone will necessarily be able to, to overcome this dysbiosis. So I outlined a number of different things, both diet and lifestyle factors and supplemental things that could be useful in trying to prevent oxygen leakage into the gut. And kind of shift back to a state of homeostasis. Butyrate being one of those things, though, that's, that's really important. So essentially what's going on is the oxygen leakage is, is happening partly because the epithelial cells that line your gut are starved for energy. And when they're starved for energy, they're not metabolizing butyrate, right? If they don't, if they don't have it. So what they do instead is pull glucose from the bloodstream and essentially this ferments to lactate and that lactate leaks into the gut in addition to the oxygen that is normally used through the metabolism of butyrate. So it's really the, the fact that there's not butyrate present, and that's what means that the oxygen that's flowing into epithelial cells from the blood doesn't get used. And that's when it ends up spilling out into the gut lumen and feeding the pathogens that we talked about. So it's essentially providing supplemental butyrate will mean that you're providing the energy that the epithelial cells prefer. They'll use more oxygen as part of their metabolism of that butyrate and won't need to do this essentially anaerobic glucose fermentation that's going to produce lactate and end up not using up the oxygen, meaning that oxygen and lactate will leak into the gut and feed Salmonella and Enterobacteraceae and a number of those different proteobacteria.

Now, what is lactate? Is there any relationship between lactate and the other things like lactose and lactase or—

No, no, no relation to lactose. No, it's essentially a very small carbon molecule, lactate. It's the same, same lactate that is produced in your muscles during exercise. So it's kind of, it's kind of a metabolic byproduct of glucose metabolism that is not using oxygen.

Okay. So the bacteria that produce butyrate are typically eating fiber too. Create butyrate, right?

Correct.

So again, I'm sort of back at this. Why not just a high fiber diet rather than supplementing butyrate? Just because some people are sensitive to that?

Yeah, absolutely. So a lot of people who are in this vicious cycle are, you know, can't tolerate any addition of fiber. In fact, a lot of them have gone down to a very restrictive diet of, you know, only several foods. So this is really, this is kind of an, again, this is an advanced strategy. So if, if you, you haven't tried a healthy diet with fiber yet and you tolerate fiber, then definitely try that first, right? See, see if increasing fiber could improve your gut health. But this is essentially, I, I really put this research review together as a way to give people some, some things to try when they really can't tolerate all of the things that we typically think of as, as beneficial modulators for gut health.

Yeah.

So often, you know, the people that are— that I'm recommending try this have often done the whole slew of other, other gut treatments and not really seen improvement. So certainly the diet and lifestyle factors are things that I'd recommend to everyone. But when we're talking about things like supplemental butyrate, or even I talked about in my article the use of mesalamine, which is actually a pharmaceutical treatment for inflammatory bowel disease that I could think could be beneficial in some cases of severe dysbiosis. I'm certainly not recommending that to the average person trying to improve their gut health. I'm really recommending that when, when we've gone beyond the typical interventions. Okay.

And so when you look at an organic acids test, I'm just curious, do you— because like, I know that it shows overgrowth of Clostridia. Do you see anywhere on there where it might be indicative of dysbiosis?

Yeah, unfortunately, the, the organic acid test I'm primarily using to look at fungal overgrowth. Because the bacterial markers are often not very specific for different bacteria. So it's— you can tell if someone has bacterial dysbiosis because they, they have high, high levels of some of those organic acids produced in the urine, but it's not really definitively telling you what profile is causing those, with the exception of a few that seem to be specific to Clostridia. So in general, I'm primarily using organic acids to look at fungal overgrowth and also mitochondrial health because mitochondria are really important for metabolizing butyrate. And if you don't have healthy mitochondria, you're not going to be metabolizing butyrate and you're going to get into that vicious cycle where you're pulling the glucose from the blood and you're leaking oxygen into the gut.

Okay, great. So we're, I guess, so between, between the longevity and the organic acids, you'd also be seeing parasite if that were a potential problem on the Longevity?

Correct. Longevity does report some parasites. It doesn't report all of them. So if, if I suspected a parasitic infection, I might use a different test in concert with Longevity to make sure that it's not missed. Like I said, a lot of— I'm not licensed to, to order tests and most people are coming to me with, with test results already.

Right, right, right. Yeah. But who would you use for parasite testing?

If, if I was combining it with Longevity, which is using, you know, metagenomics, which is more of a molecular genetic-based test, I'd probably pair it with parasitology that is using microscopy. So Doctor's Data or GI Effects would be two that, that do perform that way.

Okay. And any thoughts on prebiotics and probiotics?

Sure. Probiotics can definitely be beneficial, but it's really important to select based on strain. So a lot of people don't recognize the importance of the probiotic strain, but essentially what you'll see on the back of most supplement bottles is, for example, Lactobacillus plantarum. That's the genus and the species. But there should be a number of numbers and letters that come after that, which will tell you the strain. So for example, Lactobacillus plantarum 299V. As an example of a, of a strain. And this is important because there's numerous studies showing that different strains of the same species can have different effects in terms of, of whether they benefit symptoms or not. So there have been certain strains that have been shown to be beneficial for IBS, whereas another strain of the same species has been shown to worsen IBS symptoms. So I always recommend that people choose probiotics based on those that are evidence-based, have been shown to have benefits in clinical trials for the specific thing that they're trying to resolve.

And what about prebiotics?

Yeah, I'm not a huge fan of isolated prebiotics. I will recommend them in some cases, but typically I recommend focusing on whole food sources of prebiotics, trying to diversify the diet and getting and getting prebiotics that way. And you can do that even, you know, even on a ketogenic diet, you can still be getting blueberries and green vegetables and things like that to get plenty of prebiotic fiber to support gut health.

Although I have to say, it is pretty tough just eating vegetables alone to get anywhere near even the RDA of fiber.

That's true. But essentially, if you don't eat legumes and you don't eat grains.

Yes.

Right. So, but in, in that case, you're getting supplemental substrates from ketones. So it's essentially the combination of, you might not be getting quite as much fiber as you would on a, on a higher carbohydrate diet, but you're getting ketones, which can supplement those butyrate pathways. Right. So, and, and the, the RDA for fiber is very hard to use that as a benchmark just because it's based on a population that's not eating a healthy diet and is, is eating refined sugar and processed foods and, and things like that. So I think, I think we need to be a little bit more nuanced about that. And I, I think that the jury's still out on exactly whether, whether fiber is absolutely essential or, or whether periodic periods without fiber or with lower fiber are okay as long as you're eating a, a generally nutrient-dense diet. Including a wide variety of foods.

Okay, well, I know we are running out of time, but I have one last question related— because you mentioned glutamine. So is it— is glutamine something you frequently supplement with or suggest people supplement with?

Occasionally. It really depends on the case. It has been shown to be beneficial in, in IBS, randomized controlled trials. Typically that's a dose of 5 grams given 2, 3 times a day. So, so in some people, yes, I am a little bit more cautious in people who might have autoimmunity because glutamine can stimulate the immune system. So it really is more of a case-by-case basis whether I'll, I'll recommend glutamine. And of course, there's plenty of ways to get glutamine from, from our diet. If you tolerate bone broth, broth is a great source of glutamine, as are a lot of those other messy animal parts.

And I didn't ask about this, but what kind of dosages are you, are you thinking about with the butyrate supplementation?

With butyrate, I think it's really important to be using a dose that is more of a physiologic concentration. So a lot of butyrate salts out there, sodium butyrate, calcium magnesium butyrate, you can buy are giving or suggesting like a 5-gram dose. I prefer to use use smaller doses and those that are, that are more targeted to the colon. Again, I'm not, I'm not a licensed practitioner, but in the evidence, in reviewing the literature, it seems that lower doses of butyrate can be beneficial for healing the mucosa, whereas large, massive doses of butyrate might actually inhibit stem cell proliferation in the gut and prevent wound healing. So I think it's Butyrate supplementation is great in a lot of different conditions, but needs to be done in a way that's more mimicking the concentrations of butyrate that we would be getting if we had a healthy microbiome that was producing butyrate.

Mm-hmm. Okay. Well, this is all really interesting and useful information, and I really appreciate you coming on the show.

Yeah, thanks for having me.

Is there, is there anything I missed that you wanted to say?

I should say that if people want to follow me, I'm at ngmedicine.com. I write regular blog posts there, including about the oxygen dysbiosis connection, SIBO, breath testing, stool testing, pretty much everything we've covered. I've got an extensive article on, so if people want to check it out there, they can do that.

Okay. And I know you were doing sort of health coaching for people. Is that still happening or?

Yeah, I still do health coaching so people can go to my website and join my waitlist.

Okay, sounds good.

Great, thanks for having me on, Lindsey.

Well, thank you so much, Lucy. So if you are interested in trying out butyrate supplementation, the product that Lucy recommended in her article is called ProButyrate, and you can find that in my FullScript Dispensary. So there's a link in the show notes if you want to sign up for an account there. Do compare prices if you find the product elsewhere. And don't forget to press subscribe if you're not yet subscribed to the show, and please join my Gut Healing Facebook group linked in the show notes if you want to ask a question about gut health or suggest a topic or a guest for the show, or just give me any feedback on the show. And I've also started putting out articles based on each of my shows, so if you want to subscribe to my newsletter and get those, you can do so at HighDesertHealthCoaching.com on the newsletter page under Communications. And you can also follow my High Desert Health page on Facebook or find me on Instagram, Twitter, or Pinterest, and all those are linked in the show notes. Thank you all for listening. And here's wishing you all the perfect stool.