Speaker 1 (00:00):
Welcome to The Dr. Gundry Podcast, the weekly podcast, where Dr. G. gives you the tools you need to boost your health and live your healthiest life.
Dr. Gundry (00:14):
As you know, I’m a self-proclaimed vegaquarian. When I eat animal protein, I eat wild-caught seafood, usually twice a week. Why? Because seafood is rich in some of the most important nutrients in the human diet, like long-chain omega-3 fatty acids, phospholipids, and there’s even some cool studies showing that eating fish promotes a healthy weight. But in order to ensure you’re getting fresh nutrient-rich seafood without hormones or toxins, it needs to be wild caught.
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Welcome to The Dr. Gundry Podcast. Your microbiome may be the most important way to control your gut health and the health of your entire body, but we’ve only just started to scratch the surface of our understanding of this critical part of our bodies. Fortunately, lots of people are leading the way on this, including my guest today. He’s John Fennebresque, the co-founder and CEO of Gusto Global, a biotech company that’s on the cutting edge of answering the why and how of our microbiome communities.
And on today’s episode, John and I are going to talk all about the microbiome, its connection to the COVID-19 pandemic, and what all this research means for you and your health. John, it’s so great to have you on the podcast. Welcome.
John Fennebresque (02:49):
Thank you, Dr. Gundry. Glad to be here.
Dr. Gundry (02:53):
We know that microbes obviously talk to each other. There’s such a thing as quorum sensing, which I tell people is like getting together a rave party by texting everybody that you’re going to all be at some place. I want our listeners to understand, microbes actually do communicate with each other, number one, and then number two, microbes are dependent on other microbes for feeding, for things they can’t do. Is that a good description of what you’re saying about the ecology of the microbiome?
John Fennebresque (03:40):
Absolutely. Microbes are organisms just like we are, and they depend on food sources for new nutrition themselves, and that’s exactly why you have to take an ecological approach to the microbiome, and for the stability and health of the microbiome, you have to have those right nutrition sources. And a lot of what we’re doing in terms of developing microbiome interventions is looking at those interdependencies, which make, and we actually think that a big part of the reason for gut dysbiosis and a lot of these modern plagues that you’re seeing out there today is because of under-representation of the commensal bacteria, the helper bacteria, the bacteria that are actually providing other bacteria with nutrition sources or allowing a consortium of bacteria to go down the right pathway with their interaction with their human host. So I think that’s a very good example or analogy that you provided there.
Dr. Gundry (04:46):
A few weeks ago, I had Dr. David Kessler who was former FDA commissioner back during the Reagan years, and one of the things that he and I talked about because we’re old enough to do that, is that back when we were in medical school and really up until the human microbiome project, we were all taught that the human gut is basically a hollow tube and it’s there to absorb some sugars, it’s there to absorb some fats and is there to absorb some proteins, and maybe a few vitamins and that’s about it. And there were a few bugs down below that were basically crap and that’s all we were ever taught about this.
So you’re our old thought, and I think most of the listeners, so I could eat a candy bar and I would get energy from that candy bar, I would get calories from that candy bar. And I would absorb those, I’m sure. Are you saying that that candy bar might not feed the gut bacteria the things they need to eat?
John Fennebresque (06:01):
It may not feed the right ones. It could potentially feed some of them. I’m glad you brought up medical school, you should have dusted off the old Hippocrates book, which indicated that the gut was the origination for all diseases.
Dr. Gundry (06:18):
All disease, that’s one of my favorite lines. I don’t know how that guy knew that, but he was actually right.
John Fennebresque (06:24):
And I’m actually glad you brought up the FDA as well, because I think that our approach… I think one of the most exciting things about our approach is that we’re actually able to understand the mechanism and the rationale for why all these microbes, particularly if we were to design a targeted probiotic. For example, one of the big issues with the FDA is understanding the role of each of these microbes, and they have a lot of concern about putting live biotherapeutics into the gut because they don’t really know what’s going to happen.
Our platform, we spent two years building it, and modeling it, and confirming it in the lab. We know exactly what the roles that these microbes are playing, and hopefully we can bridge that divide with the FDA and actually start using more ecological, beneficial interventions that don’t bomb the immune system and have all these nasty side effects that auto-immune disease interventions have today.
Dr. Gundry (07:29):
Since you brought up the FDA and this area, they’ve taken a dim view of fecal transplants. Certainly, other parts of the world you can go get a fecal transplant. There are some controlled trials here. Just why would the FDA be so afraid of me crapping in a bucket and shoving it up somebody else’s rear end?
John Fennebresque (08:02):
I think it’s the broad spectrum nature of it because you never really know how it’s going to react to someone’s system, their immune system or even their microbiome. One thing that we have found that even dysbiotic microbiomes are stable microbiomes and hard to get rid of. And there’ve been some great examples of FMT, some life-saving examples of FMT, particularly for C. Diff. infection, for example. But there’ve also been some bad examples where there was an immune response to an FMT.
And I think that’s where we take it to the next step. Again, we actually understand exactly for our lead program, which we’ve done for ulcerative colitis and in preclinical animal models, very exciting results, both preventative and therapeutic positive results there. We know exactly what each of the microbes that we’re putting in to that live biotherapeutic is doing mechanistically. And we’ve also designed it, you mentioned the nutrition and interdependent relationships, the auxotrophies, the trophies, the nutrition and energy given.
We’ve designed it so it is a closed system, so these probiotics can only work with each other and have just enough energy to self-sustain and provide the missing functionality that for in our example is also patients with ulcerative colitis suffer from.
Dr. Gundry (09:41):
There’s a lot of gut microbiome companies out there, and we can send a stool sample in and they can tell me on any given day, and we’ll go back to that in a second, what my gut microbiome looks like. What are you doing? That’s different? Are they just wrong? Are they looking at the wrong things? This is one of the things that really intrigues me about your work.
John Fennebresque (10:10):
I think there’s some utility in what they’re doing, and a lot of these companies are basically providing a snapshot in time in terms of what your microbiome looks like, and that can be that can be very, very beneficial. But of course we know that based on diet and other environmental concerns that that changes over time. So in terms of therapeutic interventions, those type of datasets are really looking at missing or underrepresented microbes versus missing or underrepresented functions, and so we are looking at it at a functional level.
And again, if you don’t understand these interdependencies, these relationships between the microbes, you probably are going to miss it. You may have some impact with some patients because they have those commensal bacteria already in their gut microbiome, but for the vast majority you’re not. And I imagine that response and non-response to a lot of the auto-immune drugs typically is around 20%, and I think that’s based on the microbiome. And I imagine this approach probably won’t have that kind of… what a lot of the other groups are doing may not have as any different of a response rate.
Whereas we are trying to heal effectively the functions of the microbiome with a healthy, stable ecologically sound formulation.
Dr. Gundry (11:46):
Since we’ve not talked on camera about this, let me bring the example of the Yellowstone wolves that help make a point, and maybe you can elaborate on that. Because I think it’s a useful tool to understand what you’re talking about. As most of us know, wolves were removed from Yellowstone Park, killed because ranchers wanted them gone because they were eating some cattle, so the wolves were banished. And then what happened was that elk population who is the natural prey of wolves flourished, over flourished and elk among other things ate lots of young saplings in the streams because they had nothing else to eat.
And as the saplings died, the songbirds left, the beavers didn’t have anything to build beavers with, the fish population changed because there weren’t any beaver dams. And then when the wolves were reintroduced, all of a sudden, there’s one nasty critter, evil beast, they started eating more elk, the elk stopped eating the trees, the songbirds came back, the beavers came back. And it was this one silly animal that upset the entire ecology like you’re talking about. So are you saying that this sort of interdependent system is actually… We got a yellow Yellowstone Park in our gut?
John Fennebresque (13:20):
I think that’s exactly what we’re saying, and taking that scenario that you are just discussing. One of the most interesting things that happened when the wolves were reintroduced to Yellowstone is that the elk in particular started grazing in different places, which allowed for reforestation and stability of the rivers, which really was the real catalyst of setting that very healthy and again, stable ecology. And that’s exactly what we’re talking about.
And that’s why looking for maybe bad guy microbes, for example, only, and trying to get rid of those, that may do some good, but that bad guy microbe may just be overrepresented or underrepresented, but is still playing an ecological role. And there’s a good chance that if you get rid of that, even a nastier microbe could come in and fill that ecological niche.
Dr. Gundry (14:20):
In real estate, location, location, location. And these microbes obviously have different food needs. You mentioned, you’re right, that candy bar is the perfect food for what I call gang members. They love saturated fats and they love simple sugars. But there’s another host of bacteria that I talk a lot about in the Longevity Paradox, which are the short chain fatty acid-producing bacteria, that… And butyrate is one of the most important ones. So what are those guys like to eat? Come on, you’re the expert?
John Fennebresque (15:09):
Actually, you’re the expert on that. I think that you really understand the nutrition piece, and really what we understand is these interdependent relationships between microbes. And as I said, what we can design actually are very stable networks that can provide nutrition to each other.
Dr. Gundry (15:37):
We talked on the phone, you mentioned a fascinating Italian study looking at casein. Can you share what was discovered about bacteria that could use casein in one of two ways and how that made a huge difference in this study?
John Fennebresque (15:59):
Yeah, that’s really interesting, and it gets to what you were talking about with butyrate synthesis. And what we found, and this gets right to the core of the concept of helper microbes; depending on which microbes are present in a specific ecology, butyrate synthesis could either be good or bad. And in this case, it had to do with cow’s milk allergy in infants. And if some infants, even if they were synthesizing butyrate, had a negative reaction.
And depending on which pathway they were going down, and what we found is that the commensal bacteria had the effect of determining which pathway they went down. So it was it was it was a very interesting study and something that’s actually guided our development quite a bit.
Dr. Gundry (17:02):
Different bacteria, the pathway would be a deleterious production of say, for instance, butyrate, instead of a beneficial, depending on the bacteria.
John Fennebresque (17:15):
Exactly, exactly. Yeah. And that’s why you just can’t look at bacteria in isolation, you have to look at them ecologically.
Dr. Gundry (17:26):
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Anyway, it sounds like you’re almost running a dating service for bacteria. You’re seeing how you’re putting them in a Petri dish and seeing, do they like each other? Is this bacteria providing something that this other one needs? Is that literally how you’re going about that?
John Fennebresque (21:25):
Yeah. What you said last is a really the key, and you said it a couple of times, and it is about nutrition. And I know that people on your podcast have heard a lot about nutrition, but it’s just the same for bacteria. They need energy sources, and that is what we’re testing, is the energy is the energy exchanges between bacteria and how they function as individuals and how they function as groups.
Dr. Gundry (21:53):
So there’s what? 100 trillion different bacteria just in our gut. That’s a lot of individuals.
John Fennebresque (22:05):
It is, and that’s why this is going to be a good long project, and we continue to build and fill out our functional atlas of the microbiome. We’ve targeted a couple of functional areas particularly around some of the most common autoimmune diseases as our starting point and again, looking at samples of gut microbiomes for people suffering from those.
Dr. Gundry (22:42):
There’s the old expression, “You are what you eat,” and I added to that, “You are what the thing you’re eating ate.” And I think we got to add, you are what the guys living in your gut are eating. That actually is probably the most important message that you guys are finding out.
John Fennebresque (23:03):
Yeah. And there’ve been some really interesting studies at UC Davis in particular about breast milk and babies, and a lot of autoimmune diseases start very early because the formulations that we use for so long were designed and rationally so I suppose for the health of the human. But the reality is, is that breast milk, most of it is for the health of the gut of the baby, not for the baby itself.
Dr. Gundry (23:35):
Oh, come on. You don’t expect me to believe that for a moment. No, you’re absolutely right, and I hope our listeners realize that yeah, the mother, a large portion of the breast milk goes to feed the microbiome.
John Fennebresque (23:51):
Dr. Gundry (23:53):
So yeah, mom, you’re feeding two, whether you knew it or not.
John Fennebresque (23:58):
Right. That is the example of we want to feed our guts and those bacteria down there just as much as we want to feed ourselves.
Dr. Gundry (24:07):
Yeah. Because they’re going to take care of us. Okay. Because of we live in interesting times, what does Gusto’s research on the microbiome have to do with COVID-19?
John Fennebresque (24:22):
I think that it’s actually been pretty well publicized actually. And yeah, I think one of the… And it’s a horrible, horrible situation of course, but it just provided quite an opportunity for people in the microbiome field to really shout from the rooftops that the microbiome is important. And I think one of the interesting things about COVID in particular is just the wide range of reactions from basically being asymptomatic, all the way to death. Right?
And I think that the data continues to be more and more confirmatory that people with preexisting conditions, these autoimmune diseases that we’ve talked about before are more susceptible to having an acute reaction to COVID. And just not to get too technical, but a lot of the protein receptors of the virus that like to latch on to individuals happens in the gut in addition to other places. But it stands to reason that people who are already suffering from autoimmune diseases will have a more acute response to COVID.
We actually think that what we’ve done with our ulcerative colitis drug could be impactful. We were still pretty clinical, so this is never going to happen, but not ever, but not anytime soon, but think that it would be very beneficial to these patients with pre-existing conditions to avoid an acute response to COVID.
Dr. Gundry (26:06):
Yeah, I preach that our response is so dependent on the health of our gut, the community is in our gut, and whether we have a leaky gut or not. And again, we’re getting back to where we started, Hippocrates was right, all disease begins in the gut and-
John Fennebresque (26:27):
Including this one.
Dr. Gundry (26:29):
Including this one. You guys are, you’re doing some work with University of North Carolina and also with Tulane University? What projects are you doing there?
John Fennebresque (26:39):
We are and we’ve been scrambling to get all these in place for the last few weeks, and at both Tulane and UNC, we are getting stool sampling into the protocol when their hospitals are addressing COVID patients, so we can actually track this, and run these samples through our platform, and provide some predictions in terms of the level of response that these patients may have. So we’re doing that at both places. At Tulane, it’s actually even more interesting than that.
This quick background in terms of why this is so interesting, New Orleans for one is other than New York, New Jersey areas, probably the other ground zero in the country. Part of it probably is for Mardi Gras, but the other part of it is also a very concentrated population of people with autoimmune disease, so they have a lot of patients. And the other interesting thing about New Orleans is, after Katrina, they got a significant investment to rebuild.
And part of that investment ended up with Tulane having one of the most modern and largest biosafety level three labs in the country, and also a national primate center with the largest population of African green monkeys, which has been determined to be the gold standard animal model for COVID therapeutics. And as such, they are getting ready to test about three dozen of the potential drugs for COVID. And we are getting the samples from the primates to run through our pipeline during all this drug testing.
And with the datasets from the primates and from the people, I think we’re going to be very excited about what we can tell in terms of what drugs to get to the right people based on their microbiomes.
Dr. Gundry (28:45):
So are you saying that soon I may have to give a stool sample to get on an airplane to fly someplace?
John Fennebresque (28:56):
That may be the impractical, but gosh, I sure do you hope that the day comes that stool samples are as ubiquitous as urine samples or blood samples during our annual checkups?
Dr. Gundry (29:09):
No, I think that’s a very good point. Yeah, I don’t think the TSA would want my stool sample, at least not right now. That sounds like a breakthrough in the making. What other breakthroughs do you guys foresee? What are you working on? What are our listeners going to be watching for?
John Fennebresque (29:33):
Let me give you a little case study of something that we’re excited about, and this has to do with cancer patients. At the end of 2018 MD Anderson published a really interesting dataset correlating response and non-response to an oncology drug, one that everybody’s heard of quite a bit, Keytruda, immune checkpoint inhibitor therapy, correlating the response and non-responsive of that to the microbiome. There was a very loose correlation, but there was a clear correlation.
We were able to get a hold of that data set and run it through our pipeline and we’re able to tell with 95% accuracy, he would respond and not respond to that immune checkpoint inhibitor therapy, which on its own as a diagnostic is really exciting. For those that don’t know what that is, it’s basically a therapy that is miraculous for the people that it works on, but like a lot of these drugs that have to do with the immune system, it only works on about 20% of the people.
So it’s very expensive, it has very nasty side effects. So sure it would be nice to be able to get it to the right people, and I think that the patient stratification piece of what we’re doing is really, really interesting. And of course what would be even more interesting would be to increase the population of people who would respond to convert those non-responders into responders.
So we have actually, after we got the great preclinical results on our gut, one of eight ulcerative colitis drug, and this data set came out, and we saw how well we could stratify patients, we’ve designed our gut 115 drug as a conditioning therapy to go along with immune checkpoint inhibitors, with the hopes of really increasing that population of people who could respond to that therapy.
So that’s a pretty exciting advent and I think there are a couple of lessons learned in there. One is I think that the microbiome can be incredibly impactful and stratifying patients, and even in the existing healthcare system we have with… You hear of failed clinical trials all the time, our conscience is that there are probably a lot of promising drugs out there that aren’t working because of the microbiome composition. And we could help people really… help pharma companies and patients really get the right drugs to the right people, do better trial design.
We’re working with several contract research organizations on that concept. That cohort selection patient stratification piece, it’s exciting. I think it’s closer more near term in terms of development for us. And then just the conditioning therapy. We already mentioned before that a lot of the drugs, Remicade for example, is a drug that’s used in ulcerative colitis, which basically bombs the immune system, has horrible side effects. But still only has it works on a percentage of the people that it’s given to.
And as a first step to get conditioning therapies to the microbiome to get these drugs working better is exciting just to increase the population of efficacy of existing drugs. And then of course, we’d love to get to the point where we’re actually providing super targeted probiotics for people who have really broken guts, don’t have the time, money or discipline to fix their guts from a nutritional perspective. We really help those people out.
And then eventually foresee a world where you can look at your microbiome on an individual basis, understanding where you’re vulnerable to potential dysfunction and have a targeted probiotic to get your gut back working the way it needs to work.
Dr. Gundry (33:50):
Yeah, you’re right. It’s amazing the interplay with the microbiome and disease processes. You, I’m sure aware there’s pancreatic cancer patients have a signature, actually even oral microbiome that signifies that that’s a pancreatic cancer patient. Who knew?
John Fennebresque (34:18):
Indeed. Indeed, yeah. It’s a really exciting field because I really think we can change the paradigm. Hopefully the microbiome will wind up being the first place people look as Hippocrates figured out 2000 years ago, instead of the last place people look, right?
Dr. Gundry (34:30):
No, I think you’re right. You’re absolutely right, and that’s what I’ve dedicated my career in doing. We’ve been looking on the wrong place, and thank you and your colleagues for doing a deep dive into this place where no man has ever gone before, except Hippocrates of course.
John Fennebresque (34:47):
Dr. Gundry (34:48):
Where can our our listeners find out about you guys?
John Fennebresque (34:55):
We have a website www.gusto, G-U-S-T-O, global.com. And I’m happy to take an email from anybody email@example.com. It’s J-F as in Frank, E-N-N-E-B-R-E-S as in Sam, Q-U-E@gustoglobal.com.
Dr. Gundry (35:15):
All right. We appreciate it. Thank you very much for coming on and enlightening us, and good luck with all this work. I know it’s much needed in my opinion.
John Fennebresque (35:27):
Thank you, Dr. Gundry, and I appreciate you bringing awareness to this important microbiome field. This is an exciting place to be.
Dr. Gundry (35:35):
All right. It’s time for our audience question. Today’s question comes from Nicole McGala on YouTube. “Dr. Gundry, I just had emergency kidney stone surgery this past week. I was so dismayed to hear that spinach, leafy greens, broccoli, dark chocolate, and nuts are all things to stay away from if you are prone to stones. I started your diet this past June for joint pain, and while that has gone by the wayside, there are no words to describe the pain of this large kidney stone. What is your advice for people who get stones? I eat leafy greens, and nuts, and chocolate. These are my only vices left on your diet. I have all your cookbooks, but these easy to eat things might have to go, which is so depressing.”
Nicole, hopefully your doctor analyzed your stone and there are essentially two types of stones. There is a calcium oxalate stone, and you are advised to limit oxalate-containing foods, the number one, which is spinach. But there are equally and maybe more uric acid stones, uric crystal stones. And interestingly, the number one cause of high uric acids in my practice is fruit consumption and beer consumption. So make sure your doctor, you find out what kind of stone you have.
The other thing that’s interesting, and John might have a comment about this, there’s an interesting connection between an altered microbiome and the development of kidney stones. So all I can say is stay tuned, probably John’s going to have the answer long before anybody, but there is a connection between an altered microbiome and the development of stones.
The other thing I will say, make sure that if you are doing a ketogenic diet or you are fasting, you increase your salt consumption, because one of the side effects of a ketogenic diet is you will produce large amounts of uric acid, and you could precipitate a stone just from a ketogenic diet. I’ve seen this before, people didn’t take the advice to increase their salt. But great question, and find out what kind of stone you have. And now it’s time for the review of the week.
Speaker 4 (38:01):
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Dr. Gundry (38:36):
Here’s what Scott wrote on drgundry.com. “I started Dr. Gundry’s way of eating at the end of 2019. I wanted to eat healthier. I thought I was eating healthy up until then. I was eating a lot of dairy, fruit, yogurt, and many of the wrong veggies. I have lost plenty of weight and feel stronger and energized at 61 years young. I feel way safer and healthier. I owe an awful lot to Dr. Gundry. Someday when social distancing is not an issue, I would like to give him a hug and shake his hand.”
Here’s a handshake and a hug across the video. Scott, thank you very much. That’s why I do this, and you can do me a favor and be a perfect example and show your friends just what can happen when they change what they eat. Thanks a lot.
Disclaimer. On The Dr. Gundry Podcast, we provide a venue for discussion, and the views expressed by my guests do not necessarily reflect my own.
Thanks for joining me on this episode of The Dr. Gundry Podcast. Before you go, I just wanted to remind you that you can find the show on iTunes, Google Play, Stitcher, or wherever you get your podcasts. And if you want to watch each episode of The Dr. Gundry Podcast, you can always find me on YouTube at youtube.com/drgundry, because I’m Dr. Gundry, and I.m always looking out for you.