Episode 55 Decoding the Interactions Between Exercise, Diet, and Gut Microbiota

In this enlightening episode, we discuss the role of gut microbiota in chronic diseases, its impact on organs like the brain, and how factors like sex, diet, and exercise influence it. We throw light on the good, the bad, and the misunderstood bacteria within us, questioning the oversimplified labels of "good" and "bad" bacteria. We discuss how exercise and diet may lead to a healthier microbiome, and the potential for functional redundancy among the thousands of types of bacteria in our gut. Dr. Campbell shares her experience and research on the relationship between gut microbiota and exercise, shedding light on fascinating elements like butyrate, propionate, and acetate.

Timeline:

2:30 Gut microbiome vs. microbiota

15:33 How many different kinds of bacteria are there in the gut?

19:21 Is there a ‘training effect’ on the gut microbiota?

32:20 Fecal transplants

35:36 Microbiota and mood

41:17 Sex differences

43:36 Probiotics and Prebiotics

48:43 Pragmatic advice for a healthy gut microbiome – what should folks do?

About our guest:
Dr. Sara C. Campbell is an Associate Professor in the Department of Kinesiology and Health at Rutgers. She received her B.S. and M.S. from Bloomsburg University of Pennsylvania and her Ph.D. from Florida State University. Following her Ph.D., she completed a three-year postdoctoral fellowship supported by the USDA investigating the ability of flaxseed to reverse atherosclerotic lesions. At Rutgers, the Campbell lab investigates the intersection of sex, diet, and exercise on the gut microbiota, and intestinal and systemic health. The Campbell Lab has recently focused on the links between gut microbiota, brown adipose tissue, skeletal muscle, and environmental toxicants like ozone. The Campbell Lab has published papers on how exercise impacts gut microbial ecology and intestinal inflammation and permeability in a sex specific manner, how gut microbiota depletion impacts exercise capacity and mitochondrial content of key proteins related to oxidative phosphorylation and biogenesis, hormone deficiency (estrogen in particular) and gut health and the bidirectional link between the gut microbiota and exercise.

About the Show

We cover all things related to sports science, nutrition, and performance. The Sports Science Dudes represent the opinions of the hosts and guests and are not the official opinions of the International Society of Sports Nutrition (ISSN), the Society for Sports Neuroscience, or Nova Southeastern University. The advice provided on this show should not be construed as medical advice and is purely an educational forum.

Hosted by Jose Antonio PhD

Dr. Antonio is the co-founder and CEO of the International Society of Sports Nutrition and the co-founder of the Society for Sports Neuroscience, www.issn.net. Dr. Antonio has over 120 peer-reviewed publications and 16 books. He is a Professor at Nova Southeastern University, Davie, Florida in the Department of Health and Human Performance.

Twitter: @JoseAntonioPhD

Instagram: the_issn and supphd

Co-host Anthony Ricci EdD

Dr Ricci is an expert on Fight Sports and is currently an Assistant Professor at Nova Southeastern University in Davie Florida in the Department of Health and Human Performance.

Instagram: sportpsy_sci_doc and fightshape_ricci

Transcript

Speaker 1: 0:01

Welcome to the Sports Science Dudes. I'm your host, dr Jose Antonio, with my co-host, dr Tony Ricci. If you're a first-time listener, hit the subscribe button and like the show. Like the show you can find us on YouTube, rumble, spotify and Apple Podcasts. Our special guest today is Dr Sarah Campbell. She is an associate prof in the Department of Kinesiology and Health at Rutgers University in New Jersey. Tony loves that state.

Speaker 2: 0:31

I like it more than New York.

Speaker 1: 0:35

I think we all like anything more than New York. She got her BS and MS from Bloomsburg University in Pennsylvania and her PhD at Florida State University. Following her PhD, she did a three-year postdoc. I did not know this. She did it at USDA, which is interesting. You investigated the ability of flaxseed. This will be interesting because I do not know anything about flaxseed. You looked at the ability of flaxseed to reverse atherosclerotic lesions?

Speaker 3: 1:03

At Rutgers you do a whole bunch of stuff.

Speaker 1: 1:05

The Campbell Lab investigates the intersection of sex, diet and exercise on gut microbiota, which you are going to educate, tony and I on the Campbell Lab. By the way, you got a really cool bio. If you go to the Rutgersedu website you can see it. Recently you focused on links between gut microbiota, brown adipose tissue. I do have a question about brown adipose. Tony and I can still develop more brown adipose Skeletal muscle and environmental toxicants like ozone. Dr Campbell, welcome to the sports science dudes.

Speaker 3: 1:42

Thank you for having me. Sports science dudes. It's great to be here. I appreciate the invitation.

Speaker 1: 1:47

Tony and I were talking earlier. The gut microbiota. I mean, maybe I don't know if those words are synonymous, but they're thrown around a lot. When I was in school, and Tony and I were in school a long time ago, there was no talk about this. It didn't exist. It's almost like all of a sudden this new field shows up. It is super complicated, but everyone's talking about good bacteria, bad bacteria. You have all this stuff in your gut and you got to make sure you eat this, don't eat this exercise this way, and so I guess, start from the easiest thing in terms of is there a simple way to define the microbiome?

Speaker 3: 2:30

Yeah, sure, yeah, I mean the reality is. I mean, microbiology is a field of the study of microbes, whether it be viruses, bacteria and so on. It has actually been around for a really long time and you can actually search back to papers way back in the day talking about the good versus the bad bugs and so on and so forth. But I think it's the extreme length lately, or intense length, I would say, to health and diet and chronic disease and exercise, I think that's really made the field explode. So I think that that's a really great point.

Speaker 3: 3:06

So the comment you made early about microbiome and microbiota are used a lot of times synonymously. There is like a very minor detail and when you publish and put out grants, that detail does matter. The microbiota is a lot of time. We say, when you're talking about bugs, when you're talking about which bugs are, where, it's microbiota. If you're talking about the bugs, their environment, the DNA associated with it, that's the microbiome. So just a little different.

Speaker 3: 3:34

So if we talk about bugs, which we'll probably talk a lot about today, we collectively more say that's a microbiota, right, and then you want to delineate what microbiota, because a lot of environments have them. Right, you have a nasal microbiota, you have an oral microbiota, you have a gut microbiota, there's a vaginal microbiota, there's a lung microbiota and people are studying the odic, the ear microbiota and how that might be. So lots of different. So when you say bugs, you want to be specific, to designate the area, and the reason I say this is because each area is rather distinct. Right, the idea of your microbiota is that it works in symbiosis with the host and that space or organ or tissue or whatnot. So, and we have tried to look at, does the lung look like the gut? And there are, of course, a few key players that are in both, but for the most part, they're very unique to that individual tissue.

Speaker 1: 4:34

Okay so. So why the focus on the gut versus and I just this is something I just learned that you're dealing with different microbiota depending on what part of the body you're talking about. So, but it seems like all people talk about the gut.

Speaker 3: 4:47

Right, right. So I mean, that's a great question. I think if you're in the world of the microbiome microbiota, you hear about the various microbiomes and microbiotas and environments. But I think the reason that the gut microbiota has become such a talked about field is because of the area that all of us the three of us that you know, the majority of the listeners probably that you know tune in here is because it's majorly influenced by things like diet and exercise and we know that those things are critical to healthy lifestyle and can be linked to a variety of chronic diseases.

Speaker 3: 5:28

And there's no shortage of evidence linking the gut microbiota to numerous tissues outside of the gut as well as the health of those tissues. So I think that that's why it's exploded the way it has is because of the link I mean, and there's a direct link between the gut and the brain via the Vegas. So there's a lot of talk about gut brain access. You know, gut mitochondria access, liver access, kidney access. You'll hear probably an access gut, something or other for just about every organ, to be honest with you, and that's because the metabolites they produce. But I'm sure we'll get there at some point.

Speaker 2: 6:06

So really cool, Dr Sarah. So question quickly it to your point. It's it's very much impacted gut, particularly by exercise, by diet. So is it the one, to the best of our knowledge, that we can most acutely or immediately impact, as compared to, let's say, lung or ear or or, or they all globally impacted by both the exercise and dietary practice? I would assume Dietary practice, of course, would most influence the gut, but I could be incorrect because it's all new to me.

Speaker 3: 6:41

Right, right, and I think those are great questions. And this is part of where I probably would say I'm never afraid to say I don't know, I don't, I've not really looked into the literature on diet and say, lung microbiome per se, right, we know that there are links between things like obesity and lung related diseases, okay, which you know could potentially have a fall back on a lifestyle you know, sedentary behavior and or poor diet. But to say that I am completely aware of a direct link between those I would, I would be totally not a good Dr, sarah, if I said, oh for sure, there's got to be something, without really having thoroughly looked through the literature. No, if.

Speaker 3: 7:26

I'm being honest.

Speaker 2: 7:27

Yeah, no good point.

Speaker 1: 7:29

Now explain. You know, when you read when I have attempted to read papers on this and you try to when you look at what people write in the mainstream press in terms of the gut microbiome or micro, I guess, microbiota when we're talking about bacteria, delineate or differentiate. You have good bacteria and bad bacteria I'm not even sure how that's defined. And then also there's diversity versus, I guess, lack of gut bacteria diversity. How does that all work together?

Speaker 3: 8:04

Right, so this is always the best question. I think it generates the most exciting conversation, because I think you know there is this, you know, association of oh, certain bugs are are good and certain bugs are bad, and in some cases we know that there are, you know, bugs that are bad. I would say H pylori is probably the most common gut bug that we know that are associated with a variety of gut related chronic diseases, right, right. And then there's you know, the best example is another one right, where we're like, okay, those are predominantly going to be a pathogenic bacteria that are going to do something you know, bad, I would say, others, you know, probably get bad names, maybe not for the best reasons. I, you know, the best example that I can give and I've given this example a couple of times because it really is a predominant one is everybody had talked for a while about the mucinaphilia.

Speaker 3: 9:06

It's a big, you know, bug in the field that everybody has talked about, especially the diet and exercise field, because it tends to be higher in those individuals with good metabolic health. Right, it's inversely associated with BMI, so on and so forth. Right, acrimancium mucinaphilia. Mucinaphilia is something that loves mucus, right, so its job is to kind of constantly refresh the mucus within the gut, which that outer loose layer we know directly interacts with the microbes because it's got the sugars and the food and all the fun stuff that keeps the microbes nice and healthy and, you know, keeps that nice thick layer to protect the tissue. But then you go to the flip side and you look at all the literature in Crohn's disease and ulcerative colitis and colon cancer and you find achromancems, mucinophilia, two to three times higher in those patients as well. So is it a good or a bad bug? Well, if you're suffering from GI disorders it's a bad one. It seems like if metabolically, health wise, you're doing good and it's high, it seems to be beneficial.

Speaker 3: 10:15

So I think that there is a real need in the field to go beyond labeling good bugs versus bad bugs and what's here and what's there, and really start to get at this in understanding of what those microbes do in certain environments, whether it be, you know why is it seem to be beneficial in metabolic health but detrimental in, you know, disorders where that mucus layer is really thin down and then exposing the epithelial to this, you know, pathogenic microbe infiltration and inflammation and immune response and so forth.

Speaker 3: 10:55

So I think that activity of those microbes has become, or should become, important, as opposed to labeling it, you know, and just suggesting that diversity is critical, because that's the second half of the question you asked is you know, is diversity, is diversity? And more and more papers are coming out, you know, and even opinion and position papers coming out, suggesting that, you know, the changes in diversity aren't actually, you know, as prominent as we thought they were in the literature, just as many papers are showing no changes in diversity, despite, you know, what appears to be beneficial bugs being in that environment. So I think again, you know, diversity is an overused word in the field, in the absence of true understanding the activity of the microbe.

Speaker 2: 11:51

Okay.

Speaker 1: 11:54

And I hope that makes sense.

Speaker 2: 11:55

It does, it does.

Speaker 3: 11:56

Right. And then you think about how do you even measure activity? Right, the best way to do it is cultivate, right, put it in a petri dish. But then you're taking your one bug away from its community of trillions and trillions of bugs and expecting it to behave in the exact same way in your petri dish as you do in your, you know, environment. Now don't get me wrong. Cultivation studies are critical to understand how that microbe acts, what it can do and so on and so forth. But to assume that it's going to behave similarly by itself as it does in its community with the host is, you know, is the limitation. But you know things we have to figure out how to get around.

Speaker 2: 12:39

Yeah, so that's like everything. We to your point about labeling good and bad. We do it all the time. We feel better about something because it makes certainty, makes life easier. This is bad, this is good, so let's just get more of this. But everything appears inevitably to turn out to be more oriented on ratio and distribution of something, as opposed to good or bad. Right, like you, take a look at cholesterol is bad. How can cholesterol be bad? You make it. So it's LDL, it's ratios, it's VLDL. Sodium is bad. You don't have any sodium. You live about eight seconds without it, right? So it's the ratio of sodium to potassium that is more important than the fact that just sodium is bad. But anyway, I'm hearing this a lot to your point, sarah, is that people want to label one bacteria or one biota good, this is bad. You only need this one. And it's obviously more complicated and nuanced than that, and probably there's variation, I would imagine, from individual to individual, where the ratios might even be a little bit different and advantageous for each person.

Speaker 3: 13:44

Right, so I mean about one.

Speaker 1: 13:49

Oh, she froze.

Speaker 2: 13:50

Yeah.

Speaker 3: 13:54

Kind of complicated sometimes, right?

Speaker 3: 13:56

So again you've got your one third that's similar, your two thirds that are different, and so that complicates the issue.

Speaker 3: 14:06

But to your point, you're talking about individual bugs and maybe there's groups, and there was a term coined by a colleague at Rutgers, Li Pingxiao, who's one of the world leaders with regards to gut and diet. Initially the term was a genome interaction group, that microbes tend to work together in clusters and kind of work in concert or against other clusters. We call these now we kind of more associate the word guilds, so they work in guilds or groups and there is some evidence to suggest that you have, when you're good, groups of microbes and we say good again. But in the groups of microbes who tend to promote health are in higher abundance together, the ones that are more pathogenic tend to be in lower abundance. But there's going to be kind of this push and pull between some of those groups and I think the critical thing is understanding what types of microbes make up a guild and how that relates then to health, Because I think the idea that one microbe is going to be the end all be all to our problems is probably not likely.

Speaker 3: 15:28

Not likely, yeah, not likely.

Speaker 1: 15:29

Well, how many different kinds of bacteria are there in the gut?

Speaker 3: 15:34

Right. So that's a great question. So there's like 10 to the 12 or 13 trillion bacteria down there, so ones that we can actually identify only are in the thousands.

Speaker 3: 15:47

And when I mean thousands like the ones that we identified outlined, know what they do. So when we run hits, when we extract our DNA and go through and we match those sequences with known sequences, that's what we're doing is matching the sequences we have versus what is known to be out there. So the idea is, you tend to see the same types and groups of microbes showing up in papers, in the literature, because those are the ones that we have defined and sequenced and so on and so forth. So the amount of microbes that aren't collectively in that group might be a little well above what we know, and so I think that brings you back to the diversity. So, given we only know a thousand and we know there's 10 to the 12 or 13 trillion, how do we not know there's functional redundancy, which is very likely right.

Speaker 3: 16:49

We know when the body fails with this. This isn't a backup and it really takes a lot for the body to really fail at something. You have this in place to back it up and this in place and this in place and why wouldn't that apply to the gut ecosystem that you have several microbes that can do similar functions to ensure that that function that should be symbiotic with the host is always going on. So there's your diversity question. So you have a lot of those things, but what if they're all doing the same thing?

Speaker 3: 17:23

That's not very helpful. They might be diverse, but they might all be doing the same thing, so that's where that activity gets really important to understand.

Speaker 1: 17:33

Well, let me ask you this, since we are sports science dudes I want you to talk about, and when I read this in my mind, I'm like okay, that kind of makes sense because exercise is good for everything. They say people who exercise they got a better gut microbiome, however that's defined than those who don't exercise. So that's the first question. You know why that is. What's the mechanism? Does it matter if you do aerobic exercise versus resistance exercise?

Speaker 3: 18:06

And you were gonna ask me that, by the way, and I double-checked the resistance training literature and it's still it's like a year or two ago, so major area needing to be looked at. So anyway, sorry, go ahead.

Speaker 1: 18:21

Yeah, so okay. So there's the exercise issue, and then, in general, again I'm just guessing people who exercise also tend to eat better, so or eat less junk, maybe so there must be some interaction between exercise and diet versus, like me personally, and again this is anecdote the people who tend to eat well, all of them exercise. I have not met a person who eats well, who does not exercise, so you almost can't separate the exercise and the eating well part. So could you talk a little bit about that?

Speaker 3: 18:53

Right, so great question. So yes, the answer to your question is yes, there does appear to be a microbiota that is associated with exercise. It does appear to be a helpful microbiota. I will say what's very interesting about the microbiota and I put this out there a couple of years ago that it is like what you would consider a training effect, because there is evidence to suggest that you exercise, exercise and it alters. There are even studies out there to suggest that that microbiota will change depending on the part of season you're in, whether it be a preseason versus the postseason, versus intense training versus not intense training. That microbiota will adjust every single time. But there is also evidence to show that when you stop exercising, that benefit goes away, similar to what we think about with training adaptations. Right, if you stop running, your VO2 max will decline. It needs that constant stimulus.

Speaker 1: 20:02

So let's go back to the you mentioned. There's a benefit that may disappear when you stop training. What is the clinical manifestation of that benefit?

Speaker 3: 20:13

So I think that's the complicated question and what the three grants I have in NIH right now that hopefully they'll fund me on, are meant to look at right. So the number of studies out there that initially came out including ours in 2016, was like there seems to be this overt benefit with butyrate producing microbes, increasing butyrate as a result of exercise. Butyrate is a short chain fatty acid, along with acetate and propionate, and butyrate is definitely known to enhance colonic health right, increased cell proliferation, differentiation. And, given this turnover and this healthy interaction, we know that there's a lot of immune right System cells within the gut. We know we have both mucus and gut associated lymphoid tissues, the malts and the galts that are in the gut. So keeping that intestinal lining healthy, that turnover regular kind of keeps the balance too of the inflammation responses and the immune responses right. So if that's the case, you have this butyrate and it's making these healthy colon, chances are you're not overly inactive enacting an immune or an inflammatory response, which we know can manifest itself into a cold or a disease or something else.

Speaker 3: 21:37

So, as the literature has evolved, there have been a couple of studies, both animal and human. I think one of the big ones that made it out was a couple of years ago when Shimon and colleagues looked at the Boston Marathoners and yep had this study of 10 Boston 10 individuals roughly who completed the Boston Marathon and found a microbe that was very unique to those runners, villanella atypica, which now has become pretty popular and so they did a series of very elegant studies to really look at that mechanism and found that it was through a propionate pathway right and how it managed lactate, which in some ways for Marathoners is in training at that lactate threshold can be really important, it's okay. So now you have the early studies talking about butyrate. Now you have some distance runners talking about propionate and a lactate connection, and they took this Villanella and put it in a germ-free mouse, meaning a mouse with no microbes, just to see what that microbe in and of itself did to the mouse. And it did run and it did demonstrate and display some of those properties of that lactate and that mechanism. So that's one. More recently, in an animal study we see acetate playing a bigger role than butyrate and or propionate.

Speaker 3: 23:12

So I think some of the working hypotheses and things that we're thinking about are is it possible that exercise has several of these guilds that are responsible for increasing exercise performance. Lactate might have its own set of microbes that do something to help it. There was some studies where we use what they call notobiotic mice, which is a mouse with a known set of bacteria in there. Some were good at altering lactate dehydrogenase, some changed creatinine kinase, but not all of them had an effect on every outcome they measured, suggesting some are gonna be good for some things and some are gonna be good for other things. So the reality is right.

Speaker 3: 24:03

There's probably several different groups of microbes that regulate a variety of interactions, and we know the microbiota is important because there's more papers coming out, including ours, on this bi-directional link. So it's not just what is exercise due than a microbiota, but what does the microbiota do for exercise. So when you knock out the gut microbiota, there are these impacts on exercise, right, and so I think that's one of the ways to look at mechanisms. When you knock out the gut microbiota, what about exercise changes, and does that tell us? The microbiota might have a link to that aspect of physiology then, potentially, and performance.

Speaker 2: 24:48

That's amazing.

Speaker 3: 24:49

I mean you talk about the global?

Speaker 2: 24:50

Does that?

Speaker 3: 24:51

answer your question, though I mean I know I think it's a loaded question. I think that's the big thing. I think the bottom line is the mechanisms are not entirely clear. I think people are devising ways to figure that out. There's a couple on those, like I said, microbiota knockout, I should say, or knock down using antibiotics that have uncovered some really cool things recently. So we can talk about that if you're interested as well.

Speaker 1: 25:20

No, this is definitely a field where it seems like you're peeling, you know, umpteen layers of an onion, and the more you learn, the more you realize wow, it's just not very simple. It's almost like studying the brain, in a sense, because you can't biopsy the brain, right. Right, could you get gut bacteria out of someone without being inv? I mean, you'd have to be invasive, right, I mean?

Speaker 3: 25:47

No, but honestly they just kind of poop in something for you, okay, and you just put it and you do the extractions and so on and so forth. You know the flip side is a little bit more interesting just because we're actually in the middle of this right now. So kind of cool. So I don't feel bad about saying things. But animals we can give a cocktail of antibiotics too to really eliminate the mind-boggling Interesting. Yeah, right, get at. You know it's a cocktail of a whole bunch of broad spectrum gram negative, gram positive, anaerobic, able to try and get rid of everything you can.

Speaker 3: 26:26

I can't really do that ethically in a human. Hey, take this ginormous cocktail and you're going to have no microbiota, so let's see how that works. So we can't do that. But what we can do and what we are doing right now at Rutgers and one of my PhD students is doing this for his dissertation and we're doing it with a collaborator in Colorado, so it's a multi-site but we are taking basically a Z-PAC probably the most commonly prescribed med, probably one of the most commonly prescribed meds among athletes and giving athletes in the absence of a cold right Because that's going to confound your data as Z-PAC for a week and testing them before and after and get fecal samples and blood samples before and after to look at serum metabolomes and microbiota changes and is there change in performance?

Speaker 3: 27:24

And we figure I'm not 100% sure a Z-PAC is enough, truly, maybe, to mess with performance. Well, we probably see changes to bugs probably, but we're not sure it's strong enough. Either way, we feel like it's OK because OK, then we say the Z-PAC maybe changed microbiota, but not enough to impact performance. So it's still a safe antibiotic to give your athletes when they're ill. If it does change both microbiota, metabolome, performance, then we go back to the drawing board and say, all right, we may need to exercise some caution when giving athletes a Z-PAC, especially in the middle of the season. So we really want to make sure you get a full translation of the things that we're seeing with animal models and the human model and to what extent you can replicate some of that.

Speaker 2: 28:19

So that's phenomenal. Quick question on that Independent of putting performance aside, can something like how long is a typical Z-PAC last? How long are we taking that, if we did have a reason for that, about a week, two weeks, right?

Speaker 3: 28:40

So it lasts about that long. But a Z-PAC is really a five-day course of antibiotics. Yeah, it's usually the two pills on the first day, one pill on each additional day for five days. But it's a longer acting antibiotic so it's supposed to stay in your system for the one to two weeks, just to make sure it kicks everything out of the way that it needs to. So we're trying to get the participants, within 24 hours of taking that last dose, to get them back in the lab just to check. So it's more at the height of when that medication might be, rather than the two weeks later, just for consistency reasons, controlling for the study and all that good stuff.

Speaker 2: 29:20

But something such as the Z-PAC could make it again, regardless of put performance aside a very substantive change in a very measurable change in microbiota, then you're saying right.

Speaker 3: 29:32

It could and which microbes. It's meant to be a broad spectrum. Will it knock out? The question is in the absence of truly knowing which microbes overtly benefit exercise performance, do we know that it's knocking it out? I think, still in the absence of knowing what microbes overtly affect exercise performance, taking that antibiotic does mess with performance. That just strengthens the argument that there's a microbiota link to exercise.

Speaker 1: 30:08

Could you address both animal and I'm not familiar if there's much human data on fecal transplants and how that affects health.

Speaker 3: 30:16

Yeah, yeah, so those are. That's an outstanding question. So recently we know the FDA kind of give its little approvals for fecal transplants for things like C diff and so because that's very common and they appear to be effective for a C diff. So fecal transplants in animals let's start there and we can go to humans can be really interesting. You can actually do the fecal transplant where you take the feces from, say, your exercise animal, which Woods's group did, kind of put it in its little solution and kind of provide that transplant to another set of animals. And his data very nicely showed that you can take exercise microbiota or fecal samples, give it to not exercised animals and see if it protects against the DSS induced colitis. And it appears to have worked in that way. Right.

Speaker 3: 31:22

There are other studies because we always get the question well, if you take the microbiota and you give it back, do the animals resume their exercise performance, right To kind of full that, complete that circle. And rather than giving a transplant, what they did is they did what's called natural reseeding. So mice are copperphasic so they'll eat poop, so you basically take the exercise poop and just kind of put it back into the cage. And they did that for about 10 or 12 days, I think 10 days, and even after. So they gave them about 21 days of antibiotics. Yes, found the reduction in exercise that many of us did, refed them, reseeded them, I should say, for 10 days exercise seem to have come back and so, you know, it just kind of completes the loop, makes that evidence a little bit stronger that it does that.

Speaker 3: 32:16

So there is that aspect of, you know, a fecal transplant and that you know, humans we don't do that. So it is really, you know, a more of a cocktail of things and, like I said you know, for C diff, it seems to work. You know, the one important thing to note is the microbiota, as I mentioned, you know, as an exercise adaptation. If you stop doing it, sometimes those microbes will revert. So that fecal transplant, you have to be sure that it takes right, and so there are some studies to suggest that in some individuals it takes and it stays much longer than other individuals, which makes sense again, given that inter-individual variability. So I mean, it does appear to be helpful. With disease, I don't think we've quite gotten there to, you know, say, give a marathon, you know, a non-exerciser, a marathoner fecal transplant and this will be like hey, go run a marathon.

Speaker 1: 33:11

You know, we haven't quite got there yet, so what about the data on body fat or obesity if you do the fecal?

Speaker 3: 33:19

transplant. So yeah, some of that is really interesting. I think the best study came out of Jeff Borden's lab. The Discoordinate Twin Study is that. That's one of the big ones that you're talking about, where they kind of took the obese twin and the healthy twin and they switched their microbiotas and, yes, phenotypes started to match of the donor microbiota. So it's insane, it really is. But you know, and I think that studies like that are why and you loop back to your very first question why is it exploded so much? And it just you know some of these, you know studies have really shown that it makes a big difference what that microbiota is and how it can help foster that healthy or unhealthy phenotype.

Speaker 2: 34:05

Right, so Go ahead, tony. No, it's just phenomenal, because I mean, you know, the inter-relationships with every system are probably far more than we ever thought, right? And now we're finding this out about the gut and I don't want to move off to a completely separate topic, Joe, if you have more questions related on the exercise side, but like everything else, I have more answers for that too, so we can't get off it too much yet.

Speaker 3: 34:30

I'm just kidding.

Speaker 2: 34:32

Like everything else, sir, I think what we're seeing now is now the, you know, the gut is being associated globally with every either illness or everything that's good for you. Right, and that's what we tend to do. Also, we don't just say this is good or bad. Now we found the holy grail to every other health element, but the link. What do we think we know about mood and gut? So I was even looking at some reading this morning and many people now are attributing, even if it's a clinical depression I'm not talking about dysthymia or a low grade, chronic depression, but something that on a Hamilton or arms would be related as clinical and saying well, that is directly impacted by the microbiota too. Now, and the gut, you know, and stuff like that. Do we know if there is a relationship and if so, what mechanisms are going on there? I mean, how is mood being impacted? Is it through neurotransmitters? Do we know anything about this? It's just a serotonin production or anything like that?

Speaker 3: 35:36

Right, right. So those are all great questions, and so just remind me to get back to the hypertrophy and gut microbiome and limited oh we can go to that first, go to the next one.

Speaker 3: 35:47

Yeah, studies, and, like you know, we just did the mitochondria study, so it's really interesting that it's going Well. It's okay, we're I. Your point, though, is, I think, you know, people tend to like say now the microbiota is everything. Change the microbiota and you'll be automatically healthy. And I think, for those of us physiologists who know how, you know, both interactive but independent systems can be sometimes like it's, you know, it's always that if it's too good to be true, or it sounds too simple to be, it probably is right, and the microbiota, you know, isn't going to fix everything. Are there links between the? Lots of them, of course. Is there a link between the gut and the brain, as I suggested? Yes, it's probably one of the most well studied, to be honest with you, you know, because of that connection via the vagus nerve, because of the, you know, known microbial derived metabolites that are found in systemic circulation, that have the potential to cross the blood brain barrier right and exert some, some influence there, and so I think that you know those are are really interesting.

Speaker 3: 36:54

I was just happening to be, you know, pub-medding, right, cause our world we don't Google.

Speaker 3: 36:59

We're good, we pub-med, like I was pub-medding the other day, and there was some really interesting you know article that I didn't get to read yet, but talking about microbes being linked to exercise motivation in the brain, right?

Speaker 3: 37:15

So microbes and potential metabolites that can be linked to areas in the brain responsible for, you know, motivation to exercise, right, there was a study cause I pay pay close attention to the estrogen and stuff going on, since mine is like waning as the you know whatever these days it's so fun, but you know there's been links between, like you know, estrogen and lack of those receptors in the brain and motivation to exercise. And can you find a way to enhance some of that with you know gut and things. So there's no shortage of those studies that are out there. You know not my primary area in terms of gut brain, but these links are certainly there. There are pub-med and published articles in this area suggesting that there's this very real link, especially due to the microbial derived metabolites, which is a lot of what you know secondary bile acids, and so you know a lot of that going on in terms of the main way that we think the microbiota can act outside of itself.

Speaker 2: 38:25

Yeah, okay, phenomenal. So it is pouring enough into systemic circulation to potentially impact that, as you noted.

Speaker 3: 38:31

yep, yeah, so that's one of the important things about measuring like serum metabolomes is you know what microbes you know or what metabolites are now in system to then be perpetuating these effects. So yeah. Yeah.

Speaker 1: 38:45

I have a question about the when you look at the way people train because I want to get back to the resistance training part yeah, yeah, but there are a lot of people who don't do, who sort of do a combination of everything. They're not just pure aerobic creatures or pure resistance training. I mean, a lot of us kind of do a little bit of everything. So does that mean the adaptive response of the microbiota is sort of a little bit of everything, or is there a unique response to pure aerobic training versus pure, you know, let's call it hypertrophic or bodybuilding type training.

Speaker 3: 39:20

Right, and so I. That's a great question. So there does seem to be, because most of the studies, as I mentioned, I mean in Plumette I was like weightlifting got microbiota, resistance training got microbiota.

Speaker 1: 39:33

Three Wow Wow Okay.

Speaker 3: 39:37

Weight training and got microbiota. There was two, for whatever reason, resistance picked up another one, but it's like two, three articles legitimately and one was really interesting. It was like some I might actually I won't go away right, so the one I did find, you know, confounded. I say confounded, but some of what they were looking at because it was like eating a high protein diet, right so you know that's a confounder.

Speaker 1: 40:07

I mean right.

Speaker 3: 40:08

So is it a pro right? And then the other one was the ergogenic properties of a bifidobacterium longum isolated from a weightlifting gold medalist. Both studies were in nutrients and both 2019 and 2021. So just very recently, and those are the only two for me that pop up when I do weightlifting and got microbiota Wow. So to suggest that there's a unique weightlifting or resistance training microbiota is probably far from being elucidated. There's, like I said, you know, only those handful. I mean I'm sure you know PubMed gets everything, but there are sometimes things I mean if I were to go to Google and probably something else might pop up. But the reality is it's not as well established as the aerobic side of things. Right, most of it's been in aerobic exercise. Most of it does suggest that, yes, there's a microbiota that appears to be beneficial and helpful as a result of aerobic training, and this is consistent in males, females, animal and human studies.

Speaker 1: 41:14

So there's no sex difference at all.

Speaker 3: 41:17

No, no, I didn't say that. I said it does appear that there are beneficial changes in both sexes, but those changes are definitely a bit different. So so the microbiota within the you know males and females are different, to begin with right and short chain fatty acid profiles. So we are currently in revision on a sex difference and time course study on sex, diet and exercise on gut microbiota changes and the impacts, and there are definitely pretty prevalent sex differences that are abundant, yeah.

Speaker 1: 41:58

What about old versus young guy differences, since Tony and I are on the older side?

Speaker 3: 42:01

Right. So good question. This was a study and I believe it was rats Amica published it. It was at a Monee Fleischer's lab out at Colorado and they looked at, you know, exercise initiation and alterations and gut microbiota and young versus old right Appeared to be changes definitely more robust in a young animal compared to the old animal. But that doesn't necessarily account for which. I assume all three of us are lifelongers, right? I mean we've started exercising when we were younger and maintain, I mean short of periods of time where, like you know, where some of us maybe have been very sick or some kind of kept up a pretty regular exercise routine. So does that mean that exercise manifested changes that have been fairly salient through our aging? I think that that's a great question and probably one that hasn't been answered yet.

Speaker 2: 43:03

It has in many other systems. So I mean we don't know, but it might be rational to assert that it has. You know we could preserve it Right.

Speaker 3: 43:12

So if you start exercising earlier, you benefit from those adaptations that that maybe makes a more resilient gut microbiota, even as you age. Yeah, I mean, I don't. That's a reasonable hypothesis, for sure.

Speaker 1: 43:25

Okay, delving into the supplement side, tell us a little bit about probiotics. Are they worthwhile, worthless, and also the prebiotic category. So talk a little bit about that.

Speaker 3: 43:37

Yeah, so you know the pre and the probiotics, though the probiotics are the bugs themselves, right? So the prebiotics are the foods that you know, fermented kind of things that go in there and get made into those short chain fatty acids. Probiotics I am a, you know, when it comes to supplements, I am a do no harm, right so. And probiotics definitely do no harm, so I, you know. I think every person you talk to in a probiotic will tell you their story, or an ex user for probiotic. They either totally work for you or they don't at all work for you, right?

Speaker 3: 44:19

I think you know probiotics are again once you start taking something to change the gut microbiota, you have to take it, and when you remove that stimulus, the gut microbiota will revert to what it's comfortable at, which is your microbiota. That gets kind of settled in at two or three and then has changes throughout the life, you know. You know puberty will induce something and this will induce something else, and so on and so forth, but it tends to kind of stay fairly, you Right? So if you start, the probiotics, keep taking them, especially if they work for you. If you know, if you take them and you stop and you don't notice anything, then perhaps it hasn't done much Right. I mean, most of the probiotics I still think contain very similar still versions of lactobacillus and bifidobacterium. I don't think that they have moved too far away from a lot of those strains because they tend to be the ones that we know the most about. But given the earlier parts of our conversation where we said well, we only really know how a few thousand work, there's not.

Speaker 1: 45:27

Right.

Speaker 3: 45:27

Are there definitely untapped ones that we don't know about. That could be more important. So probably maybe, and they just haven't been looked at yet. I think prebiotics are again, that's again linked to your diet. Are you incorporating those high fiber foods or fibrous foods as part of your diet? That will then manifest the production of those short chain fatty acids. And again, if you're eating them and you notice good changes to your gut microbiota, don't stop, because once you stop it'll go back and unfortunately you see this kind of reverse or reversion of the gut microbiota to whatever it was after you stop or give up, whatever that intervening aspect is.

Speaker 3: 46:14

So most people will say feed the bugs the prebiotics, use the probiotics If you are deficient, maybe have some sort of gut related issue that you feel benefits them. I think most people would say feed the bugs and we know for performance, I believe you guys have a position stand on probiotics Like it's not really. It's kind of not direct, it's an indirect organic on me, potentially kind of lessening sick time and things like that, just because I think the mechanism of how probiotics work is still totally unclear. I mean, for a while there the NIH was putting a lot of funding into how to probiotics work, because everybody seems to be on them and gut microbiota is big, and so let's figure out how they work. And so it says something that within the last 10 years there were major calls for proposals of the NIH to understand how they work. Right.

Speaker 2: 47:10

So one quick question, and it's just hard to answer, I know, without taking direct measurement. What is you said? Some people take them and think it works right. What are we looking for? What would you if, outside of direct measurement of what's available? What do we mean by work? And I'm not being a wise guy Like. What would we look for? Yeah, no, totally Right, yeah, no, what would that mean?

Speaker 3: 47:35

Right. So, short of, like you said, checking to see what that gut microbiota looks like before and say after your probiotics? And were you deficient prior to in some of those probiotic bugs which we do know are beneficial, which is why they're put into the probiotics, and now they're there acting as a guild, suppressing pathogenic guilds, right In that whole interaction that we were talking about? So you don't know that and, like you said, in direct measurement, I think the biggest way to see if they work for you is, you know, alleviation of symptoms For someone, say, suffering. You know someone feels bloated or whatever all the time. I think the biggest thing is do your symptoms feel alleviated to where you know the comfort of your day is a lot better? You're like okay. Well, if you're noticing that, then you probably are like, okay, these, these are probably working for me.

Speaker 2: 48:28

Got it. Does that make sense? Yeah, totally.

Speaker 1: 48:31

Yeah, we're almost out of time. I want to be respectful of your time, so, really, one last question, and it's a pragmatic one. So if someone were to ask you how do I, what are, what are the things I can do in terms of diet supplementation and exercise to have a healthy gut microbiome, you would and assume they know nothing about science. Yeah, yeah, what would you? What would you tell them to do?

Speaker 3: 48:56

Right, so great question. So, based on the literature available at at the moment, right, engaging in at least some aspects of aerobic exercise, you know. So the, at least starting with the, something like you know the 30 minutes five days a week and, you know, working your way up. But engaging in aerobic exercise because we do, we do know that's beneficial in both men and women who exercise. Right, you know diet wise? I think they're.

Speaker 3: 49:25

You know there are probably lots of diets that haven't been looked at with regards to the gut microbiota. So you know saying like, oh, high carb, low fat, low fat high, you know, or, or. But we do know. You know those prebiotic type foods that facilitate the activity of those microbes that are going to be responsible for producing short chain fatty acids and other metabolites are typically assumed to be more healthy. That doesn't mean you don't eat probiotic type foods, like you know the yogurts and the. You know all of that good stuff as well. In terms of you know supplements, I think that's probably also really understudied area in terms of what does and I probably could PubMed it, or one of you like, creatinine, gut microbiota, what does creatinine? We know that that's extremely beneficial for performance and a variety of other things, but what does that do to your gut microbiota? I don't know that. We know that, yet that's a great question, right.

Speaker 3: 50:25

So maybe I smell a study Bruin guy or dudes we have everyone to say it, but yeah.

Speaker 3: 50:32

But you know, I think probiotics is probably the biggest you know supplement that's out there. And again, that's really a very you know personal thing. If it benefits you, great. If it doesn't, but I think the biggest thing is for sure we know aerobic exercise helps in both men and women, for sure we know. You know the soluble, insoluble, fiber type diets are beneficial for those microbes as well. I think a lot of stuff outside well, and I should say, and we know high fat diets are typically bad.

Speaker 1: 51:00

Bad, okay, okay, okay, Right, so I should keep eating my kimchi and occasional sauerkraut.

Speaker 3: 51:07

Yes, absolutely, why not Delicious as well? So might as well enjoy a little bit of life, right.

Speaker 1: 51:14

Any final thoughts, Tony, for.

Speaker 2: 51:16

Fascinating. I mean it's just an incredible, it's a universe, right? You're talking trillions. I mean I don't know what. Are there trillions of galaxies out there. You're talking numbers that are that you can't quite fathom, and it's really exciting. You gave us a great overview, sir. I thank you and and I'm really looking forward to what the field will tell us in this discipline in the future and your work, because it's in infancy. And when you're talking about trillions of cells, well, I should say trillions of you know those organisms, boy. There's a lot to learn and a lot going on here. So we got a fun future ahead, you know. Yeah, definitely Sure.

Speaker 1: 51:55

Well, thank you. Thank you, Dr Campbell. I mean, this is quite the edification. I learned a lot more about microbiota and the microbiome than I have in the previous five or 10 years. So appreciate your time and thanks for being on the sport science dudes.

Speaker 3: 52:11

Yes, well, thank you so much for having me. It was a blast. I appreciate it Great. Thank you again.