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Guest Bios:

Michael Chapman, ND, has a doctorate in naturopathic medicine and is currently the director of product innovation at Genova Diagnostics and cohost of their podcast, The Lab Report. As an educator, Dr. Chapman consults with integrative and functional medicine practitioners and has delivered presentations nationwide at medical conferences. Dr. Chapman is also a writer and contributor to the latest edition of Textbook of Natural Medicine by Joseph Pizzorno, ND, authoring chapters on urinary organic acid testing and urinary porphyrin analysis.

Patricia M. Devers, DO, is a board-certified internal medicine physician with a specialty in hospitalist medicine. She currently serves as the chief clinical officer at Genova Diagnostics and cohost of their podcast, The Lab Report. After 20 years in clinical practice, Dr. Devers has been extensively trained in functional medicine and has lectured throughout the country and internationally. Dr. Devers is also a medical affairs content writer and contributor to the latest edition of Dr. Joseph Pizzorno’s?Textbook of Natural Medicine.

Transcript:

Kalea Wattles, ND
The skin is the largest organ of the body and hosts a diverse microbial community. The health of the skin and its microbiome have been linked to the health of our gut, and vice versa. Known as the gut-skin axis, this bidirectional connection between the skin and the gut is an important relationship to consider.

Michael Chapman, ND
The skin is tremendously diverse in its microbiome as well. Like, there’s over 1,200 different species in the skin microbiome, which is actually quite similar in diversity to the gut. And like Patti was saying, because of these different types of environments that your skin has, there’s different populations of organisms that live there. So the microbiome that exists on the dry part of your arm is gonna be very different than the microbiome that’s gonna exist on your scalp or another oily place.

Kalea Wattles
In this episode of Pathways to Well-Being, we welcome Drs. Michael Chapman and Patti Devers from Genova Diagnostics, discussing the connection between skin and gut health. Genova Diagnostics is sponsoring our AIC Pre-Conference opportunity this year with Jeffrey Bland and Mark Hyman, so we’re happy to sit down for this chat about gut and skin health before the conference. Welcome to the show, Patti and Michael.

Patricia M. Devers, DO
Great to be here, Dr. Wattles, it’s an honor, thank you.

Michael Chapman
Thank you so much. Yeah, can’t wait to have this chat.

Kalea Wattles
Well, we’re here talking all things microbiome today, and I think our listeners are most familiar with the gut microbiome, but the microbiome of the skin might be a more novel concept. So I thought we should set the scene today by talking a little bit about the role of the microbiome in our skin health. So give us the scoop and tell us a little bit about the function of these microbes on our skin surface.

Patti Devers
Right, I think a good place to start is just a reminder of how important the skin is. As you just said, Dr. Wattles, skin is the largest organ in our body, right? It has a lot of really important things that it does besides be a physical barrier. It actually is in charge of water balance, right? Preventing excessive evaporation of water and the tight junctions of the epithelial cells and the keratinocytes. They can, they kind of monitor electrolytes and water movement based on exposures. I mean, we’re exposed to a lot of things in UV light, environmental triggers, so they’re important to be osmolyte transporters for water balance. I always think about if you have a burn patient, someone who loses skin, we’re always very concerned about their water balance and replacing water. So the skin is important for that. It’s also important for regulating temperature.

But I think the biggest thing we don’t talk about is the fact that it is a barrier between the outside world and the inside world. It’s a physical barrier, and like we said, there’s tightly controlled differentiation of those cells to give that protective barrier against bad things in our environment. But it’s not just a physical barrier. There’s also a chemical barrier. So our skin has things like lipids or free fatty acids that can maintain a lower pH of our skin to prevent us from bad bugs or things that might harm us. There’s also an immune barrier, both innate and adaptive within our skin. Innately, our keratinocytes make things like interleukins and the AMPs that come from some of these cells to help protect us. There’s beta defenses on our skin that are bactericidal. There’s also an adaptive immune response within our skin that kind of helps to make Treg cells and moderate the response. But there’s also the microbiome. There are bacteria that live on our skin, and you think about the skin as a whole, there’s a lot of different types of skin on our bodies, right? There’s dry skin, like on your hand or on your buttocks, it’s dry. There are moist parts of our skin, like the axillary regions or your inguinal creases or your antecubital fossa. So that’s a different kind of microbiome that would live in that place. Then there’s also oily sites of our skin, like on our face, the glabella, or the ALR creases are in your head. So these are all different environments that have very different microbiomes that live there to keep us healthy. And Michael, I don’t know if you wanna talk specifically about the diversity of the skin microbiome in these areas.

Michael Chapman
Yeah, I mean that was like a good synopsis plan, I would say, you know, it’s like the gut microbiome. We think about the GI microbiome a lot. I think in our practices of, and we know how diverse it is, but like the skin is tremendously diverse in its microbiome as well. Like there’s over 1,200 different species in the skin microbiome, which is actually quite similar in diversity to the gut. And like Patti was saying, because of these different types of environments that your skin has, there’s different populations of organisms that live there. So the microbiome that exists on the dry part of your arm is gonna be very different than the microbiome that’s gonna exist on your scalp or another oily place because ultimately, these bugs are there because they’re trying to kind of adapt with us, right? They’re using the things that our skin is producing for energy components and making their own metabolites and things like that. So it truly is a commensal relationship that we have with these groups. And I guess I would just add, from the diversity perspective, is with any type of interface that our body has with the outside world, there’s gonna be… And that includes the GI, right? The GI is ultimately a place where we interact with the outside world. And so, of course, in those areas, you’re gonna have a barrier, you’re gonna have a protective component. And then right at that interface, there’s gonna be a microbiome because as we all know, we’re sort of swimming in this sea of microorganisms. So we have to kind of come through with this adaptation to a microbiome so that we can actually keep ourselves as safe as possible from the potential threats from the outside world.

Kalea Wattles
Indeed, it’s funny, when I talk to patients about the skin microbiome, it’s like sometimes it’s kind of creepy to think about all these organisms on your skin, right? But it’s helpful to remind everyone of all of these amazing benefits and all of these functions of those microbes. Now it’s, I think we have an understanding of how we can shift the microbial balance inside the gut. You know, there’s so many inputs, including the foods we eat. What I’m not as familiar with is how we shift the microbiome that’s on our skin in all of these different locations. And I understand there’s this bidirectional communication between our gut and our skin that allows these systems to talk to each other. Will you tell us a little bit more about that communication and how microbes in one location might influence the other?

Patti Devers
Yeah, I think important, I think Michael said something profound there, how alike the gut and the skin is. They are both directly seeing the outside world, right? They’re both heavily vascularized. They’re very densely innervated. They both have their own specific microbiome diversities that are distinct and only there. So that’s important. And so the question is, how are they interacting with each other? And there’s a lot of ways, but I think the one that most of us think about are the gut microbiome metabolites.

So when you eat food, your bacteria, the commensal bacteria in your GI tract take that food and they break it down. They make really important metabolites, as we say on our podcast, the stuff the bugs make, right? So the stuff the bugs make can get into your systemic circulation and do some really important things or also some really bad things. So when I think about what’s the most common way that our microbiome from our gut interacts with our skin, it’s by way of these metabolites. And it’s things like short-chain fatty acids, which I’m sure most of the audience is well aware of if they follow this particular show. So short-chain fatty acids we know are anti-inflammatory. But what you don’t know is when they get into systemic circulation, they also specifically affect your skin. And so it modulates the proliferation and differentiation of your actual skin cells, the keratinocytes, and they’re anti-inflammatory.

You also think about other things made in the gut. Things like GABA made in the microbiome goes into systemic circulation, does a lot of great things, but as it relates to the skin, it actually can inhibit itching, which is fascinating. And I also think about things like serotonin. Most of our serotonin is made in our GI tract, and a lot of people don’t actually realize that. And serotonin is important, and it’s important because it regulates skin inflammation in addition to changes your mood, but in circulation, it can affect skin inflammation, skin pigmentation. We also think about things like dopamine, which is also made in your gut. When that gets into systemic circulation, it does a lot of stuff, but it also can alter hair growth, which is fascinating to think that these things that your bugs are making can alter that. And we also think about, conversely, how does the skin speak to your GI tract? And I think the biggest example of that is UV light, right? Sunlight, it hits our skin, we make vitamin D, and vitamin D and circulation has a lot of great things that it does, but it actually can alter and improve your microbiome. And people who have adequate levels of vitamin D actually have better diversity in their microbiomes. And so you can see that there is this bidirectional signaling, just as a high level. Those are the big things I initially think about, but there are lots more.

Michael Chapman
Yeah, and just to piggyback a little bit, if I may, Kalea. I think one of the things that’s interesting too, coming from, you know, as kind of your, we’re a little bit focused on GI microbiomes overall, and we’ve been studying that for a long time. So when you start to look at the research around the gut-skin axis, it’s kind of funny because you see a lot of areas in the research articles saying something like, “Well, we know these things are connected because we’ve got all these causal association studies. But more studies need to be done to figure out exactly why they’re connected.” And so there’s a part of me that what I see is the mechanisms are actually very, very similar when you study the GI microbiome and you study the skin microbiome.

And ultimately, I’m gonna play a little bit to your naturopathic roots as part of this too, is like we start to see that some of the ways that you treat these things are actually kind of the same. And that’s one of the awesome things about functional medicine is like you get to study these complex systems, but then when it comes to like, how do I modulate these things, you actually get back to some of these really core basics. And so, when I’m thinking about that connection between the gut and the skin, I really am thinking about kind of two main concepts. Patti was talking about the bacterial products. And so we can influence what our gut microbiome is making by what we’re putting in our mouth, right? The different foods that we’re eating, fiber, things like that are going to change how many of those beneficial products our gut microbiome is making. Those then enter the circulation, and they actually end up going to our skin. And so things like n-butyrate and short-chain fatty acids help to modulate inflammatory signals across the whole body, not just in the microbiome.

And then the other main component that we see over and over with the connection is inflammation. Because what happens in the GI tract is whether it’s coming from some sort of food issue, whether it’s coming from a dysbiosis or even something like inflammatory bowel disease, inflammation in the GI tract ultimately ends up systemic. And so, greater levels of inflammatory cytokines will reach the skin, and they will also trigger their own changes in the skin microbial population. And it will also create a predisposition to inflammation on the skin in and of itself. So you can kind of get into which inflammatory cytokines and which bacteria and which microbes and some of the nitty-gritty details. But if you just go high level, you’re really talking about inflammation and diet, right, which are two things that we focus on so well here in functional medicine.

Patti Devers
Yep.

Kalea Wattles
Beautifully said, and it’s a perfect lead in to my next question because we see that there, that these imbalances in our gut microbiome and these metabolites can result in skin conditions like acne and atopic dermatitis, rosacea, psoriasis. Do we see different kind of a microbial imbalance patterns that are associated with these conditions? Is there distinct treatment or, Michael, like you said, is it just kinda, we treat the pillars of addressing dysbiosis, addressing intestinal permeability and inflammation, and it’s going to clear it up no matter what it is? I’d love to hear more about that.

Michael Chapman
Yeah, I mean it’s sort of yes and no, and both, and all the above and all those things, right? And it does, each skin condition is a little bit different. But a lot of the research is actually very interesting around that connection between skin and gut with respect to things like psoriasis or acne, eczema. Psoriasis is an interesting one because it’s an immune-mediated attack, right? It’s an autoimmune condition. And so it shouldn’t surprise anyone that to find that inflammatory bowel disease is a common comorbidity with psoriasis because, as we know, autoimmune diseases, once you got one, you’re much more likely to have two, three, four. They just compound on each other. And so with psoriasis, it seems that the microbes are actually associated with low levels of Akkermansia. And if, you know, your listeners are familiar, Akkermansia is a very important commensal organism in the gut that helps maintain kind of the protective mucus layer of the GI tract. And then they also tend to have people with, again, Crohn’s colitis or inflammatory bowel diseases. They have lower levels of Bacteroides and, basically, a whole bunch of other organisms in the gut microbiome. They have a kind of a low total abundance, it seems, when you look at some of the research.

And so when you look at treatment for that, oftentimes, things like probiotics and prebiotics, that to increase the gut microbiome seems to be very helpful for the psoriatic symptoms related to inflammatory bowel disease or even psoriasis by itself. And that makes a lot of sense because like we were saying before, a lot of the things that our gut microbes make are things like short-chain fatty acids, which help repair our gut lining, and therefore, they reduce the likelihood of inflammation getting into the system. And they also produce beneficial things like short-chain fatty acids, which can lower inflammatory signals. So, you know, that’s one interesting feature of something like psoriasis.

Eczema… Eczema is a little bit different because it’s more of an IgE-mediated process. And so when you look at the beginnings in the etiology of eczema, what you tend to find is more of what we think of as a Th1 or Th2 disruption in the system. You have an imbalance between kind of two main facets of our immune system. And this is similar to what we find in things like allergies and other atopic conditions. And so one of the interesting things there, Patti mentioned before GABA, and interesting story about eczema was like one of the original tales and ideas around some of these skin conditions was that maybe it was brain mediated, maybe the brain wasn’t producing enough GABA because GABA really seemed to rebalance that Th1, Th2 symptom system and then lower inflammation. And so, what they didn’t realize, perhaps at the time, and what we now know is so much GABA is actually produced in your gut by microbes. So whether it’s, again, a deficiency in your overall microbiome in your GI tract leading to low levels of GABA, whether it’s also this idea of permeability so that inflammatory bacterial products are making it to your system, causing inflammation. This seems to be multifactorial as far as driving inflammatory processes in the gut. And, you know, each one of these skin conditions has a little bit of a different tale, acne’s a little bit of a different tale, but those are just a couple interesting ones and where the research is at with them.

Patti Devers
Yeah, can I piggyback on what you just said, Michael? Because to your point, we think about things like psoriasis and inflammatory bowel disease, also quite similar if you think about it, they’re both immune-mediated, they’re both chronic inflammatory diseases that both relapse and remit throughout their courses. So there’s a lot of things that are similar. Patients with IBD have a, like, higher likelihood of having psoriasis. Patients with psoriasis have a higher likelihood of having IBD. So clearly, there’s a really important connection there. And so it comes to that whole point of like, what is the connection? Why is this so? And first of all, there seems to be some bit of a genetic component to this.

With whole genome sequencing, they’re seeing that there are some shared loci between the two diseases, but we know our genes are not our destiny. And so it comes to the next piece, and it brings me to increased permeability, cause, Michael, you said these are autoimmune conditions, and we know that part of the triad of autoimmunity is increased intestinal permeability. And so what happens when you have increased intestinal permeability? Well, it kind of messes up the immune homeostasis of your GI tract. And when that happens, the microbiome can’t signal the immune system. The GALT, the gut-associated lymphoid tissue can signal all over the body, including to the skin. And when there’s a disruption with increased intestinal permeability by whatever reason, including inflammatory bowel disease, those signals get disrupted. And so with a profound dysbiosis or an increased intestinal permeability, this can also lead on the heels of what Michael was just saying with Th1 and Th2, but it can also overstimulate the T helper 17-driven immune response. And so, remembering back the T helper 17-immune response has to do with protecting mucosal barriers, which makes sense. There’s a disruption, there’s an increase in neurointestinal permeability. It’s gonna drive up that pathway of T helper 17. But with that, that causes a problem because in communication with your skin, it can also release cytokines. It’s overdriving this immune system and leads to systemic inflammation and skin inflammation. So the two, inflammatory bowel disease and these inflammatory skin conditions, are directly connected via things like increased intestinal permeability and kind of messing up the inflammatory and immune signals between the two.

Kalea Wattles
This makes good sense to me. And my clinician brain, I’m gonna pose to you a clinical conundrum that I sometimes find myself in selfishly to get your advice. Because what if I have a patient who has these skin conditions that look inflammatory to me, like they have psoriasis or maybe they have ulcers, right? Like there’s clearly some inflammation happening. But when I’m doing my review of systems and I ask them about their gut, they’re like, “It’s fine. I have a regular bowel movement, like I feel good.” Should I still go investigating into their gut health? Is comprehensive stool analysis still a good choice for me when, you know, the patient’s perception is that their gut is fine?

Patti Devers
I think we have the same answer. Michael, you wanna go?

Michael Chapman
Sure, we could go back to Hippocrates where, him talking about all diseases start in the gut. I think one of the things I would say is like the clinician brain too, is how often does somebody tell me that their gut is fine? And then when I do further investigation, I realize that it’s fine for them because they’re used to it, but it’s actually not fine. And then I would say too, you know, we often see that one of the major reasons why a stool test is often ordered in patients, aside from just like the obvious they have a GI presentation, is actually skin conditions because of how closely related the GI tract is to overall skin. Not just in the sense of what we were talking about with inflammatory signals, but even from, you know, more of a philosophic sense, of it being an emunctory.

Our GI tract has phase 3 detoxification, and our skin is a huge detox organ, right? So there’s just that natural connection between even the, what their function is in our physiology. And so, I would say, yeah, and a lot of times that there’s a skin presentation, we would be hard-pressed to find that there’s not something going on that could be worked on in their GI tract, whether, are they producing enough short-chain fatty acids or is there any low-level inflammation? Even some of the things that might not be directly associated with a symptom, like a microbiome deficiency, right? That’s not something that you would necessarily pick up. You can even look at kind of patterns in the microbiome within the GI tract to say, is this pattern of bacteria more likely to be generating inflammation as compared to maybe a more balanced microbiome? And so those are some of the things that, you know, you weren’t running, if you were always getting what you were expecting when you run a test, then you wouldn’t need the test. The test is to show you what you aren’t expecting. And so I think that’s one of the reasons why I would say, yes.

Patti Devers
Agree.

Michael Chapman
Understanding the, yeah. Understanding the GI tract is, agree.

Patti Devers
A 1,000%, and even, you know, something like increased intestinal permeability doesn’t always have specific symptoms, right? We see subtle changes on stool testing with fecal secretory IgA being elevated, and it’s a problem because if you have, you know, impaired gut barrier, some of the toxins and things that you would’ve excreted are now in your systemic circulation. And, Michael, you and I interviewed someone on our podcast talking about this, where they’re biopsying psoriatic lesions and actually finding lipopolysaccharide within the lesions, LPS from the gut bacteria. And so, even if someone has no gut symptoms, Dr. Wattles, I’d be hard-pressed not to get a GI stool test on all of these patients who have any type of inflammatory skin conditions, to Michael’s point.

Kalea Wattles
Mm-hmm, makes sense to me. So let’s say we do our testing and then, because we love functional medicine, we are going to implement our 5R program for gut restoration, right? How long after we implement a treatment plan should we expect to see changes to our skin improvements in these inflammatory skin conditions?

Michael Chapman
Yeah, I mean, this is one of the things too where there’s never a perfect answer, and we have to go back to personalization, whether we’re talking about, you know, what’s the right diet everyone should be on or the right multivitamin. Like this is where functional medicine plays such an important role, is that understanding how symptoms and how a disease is either progressing or improving is going to be very person-specific. And it’s likely going to be specific as far as how directly you’re hitting the root causes around it too. You know, I think in all reality, we tend to see the microbiome be able to change rapidly, you know? With a dramatic change in the diet, we can actually change the microbiome in someone’s, in overall GI tract very quickly. It’s a fast-adapting system, but the downstream consequences of that aren’t likely to be as fast-acting, because we’re talking about shifts in inflammation, right? How often, how long does it take a normal wound, you know, when you scrape your knee or you get a bruise, how long does it take that entire process to heal? It takes a good bit of time, you know, sometimes weeks and even longer. And so, something as, I guess, complicated as psoriasis or eczema, a skin lesion that’s a downstream effect of either intestinal permeability or just general GI microbiome dysbiosis, then that’s probably gonna be a little bit longer, right? It could be months.

And sometimes we use a little bit of the idea around, you know, did it, how long was this, did this take to develop? Because that might give you a little bit of an assemblage of how long it might take to correct. Now that being said, if you’re really pulling on all of those root causes and getting those obstacles to cure out of the way, then you could probably have a pretty decent turnaround in a rapid period of time. And it may not take six months, it might be a lot better within a period of one to two months. So it does tend to depend on each patient how complicated the system was, how many of the root causes you’re correcting, and whether you’re getting to all the root causes, cause right now, we’re obviously talking about the microbiome causes, but there’s other triggers too, right? And we can even touch on a little bit of some of those triggers as well. So that’s kind of the short and complicated version of that answer.

Patti Devers
That was a good answer.

Kalea Wattles
The doctor answer, “It depends.”

Michael Chapman
Yeah, exactly that.

Patti Devers
Yes.

Michael Chapman
Exactly right.

Patti Devers
Yep.

Kalea Wattles
And you even have me thinking about, kind of on the flip side, of how quickly there can be communication. I’m just thinking about the elimination diet and how when we have patients in the reintroduction phase and in that 72 hours after they reintroduce a new food, we’re having them watch for rashes or itchiness or flushing, and how quickly we can see some of those skin changes when they eat a food that they’re sensitive to, which is fascinating.

Michael Chapman
Yeah.

Patti Devers
Yeah.

Michael Chapman
Yeah, absolutely. Especially if that connection I think has already been established, right? Especially if there’s already a certain degree of intestinal permeability that’s been going on. Systemic low-level inflammation, you know, a sed rate can certainly take a lot longer or a CRP if you’re measuring kind of this systemic body burden of inflammation. You know, those might be a little bit of predictors of how long of a course it might take for something to resolve as well. Because really, we’re just trying to lower the overall body burden of inflammation while we’re correcting the permeability and the GI inflammation that’s underneath it.

Kalea Wattles
I think you’ve both made a strong case for looking into the health of the gut, and we know why we need to do that. But is there a situation, can you make a case for shifting the microbiome of the skin topically? Is there a situation in which we might wanna apply something topically rather than going inside? Or maybe it’s even, I don’t know if palliative is the right word, but something that we do while we work inside the gut just to give symptom relief.

Patti Devers
I mean, I think you could do both, right? I would say that skin conditions are the best example of functional medicine at work, right, starting from the inside out. Clearly, if patients are suffering, you can do both and start here and start there. But I will also say, interestingly again, and guests that we’ve interviewed in the past as it relates to the skin, we think about diet, we think about nutrients, right? We think about things that we eat. We’re not exactly what we eat, we’re what we digest and absorb, in essence.

But there are some nutritional things that you can take internally but also put on your skin that are antioxidants. So you think about things like vitamin A or many of the vitamins and vitamin A for specifically because it has a derivative called retinoids, right? And so we know retinoids are important for the skin that help with hair and nail growth, C production. So we know about retinoids, we know about vitamin C, these are antioxidants. And so we had a guest not long ago who actually said she would make topical things out of some foods and put it directly on her skin because they were antioxidant, but they are foods, right? And so you also think about dietary nutrients that you need to eat and digest to also help things like some of the minerals like calcium, phosphorus, magnesium, and zinc, some of the co-factors for some of the really important enzymes throughout your body. And not only throughout your body and your GI tract, but also on your skin. And a lot of people think about selenium, right? Selenium’s an important mineral because not only is it a co-factor of a lot of things, primarily in your thyroid, but it’s also been, like it’s really studied as it relates to wrinkles and reversing the sun damage of UV rays.

And so, when I think about some of these nutrients, like I said, some people take various foods and actually put them on their skin, and not necessarily, you know, commercially created products, but some of these really important antioxidant foods that you can both ingest and put something on your skin. But I also wanna talk briefly about essential metabolic fatty acids. I wanna talk about omega-3s because of all the nutrients, omega-3s are the one I think is the most obvious as it relates to your skin and your GI tract. And so you remember that in patients who are omega-3 deficient or insufficient, the very least, they have a lot of problems with their skin, slower healing, peeling of the skin, but they also develop that bumpy rash on the back of their arm, as you’ll recall, that follicular keratosis. And you’ll see that directly on their skin that they’re omega-3 deficient. But we also know how important omega-3s are in the GI tract for gut barrier for decreasing inflammation. So yes, you can start with the gut, heal the gut, but some of those nutrients you can also ingest and some you can actually put directly on your skin and not necessarily have to use a commercial product, I would say.

Michael Chapman
Yeah, just to say one thing on that too, I think this is an area that like in the research where it says we know some things associated, but we don’t know why, I think there’s a lot of area of opportunity for this.

Patti Devers
Yeah.

Michael Chapman
We know there’s palliative things out there, even things like steroids that, you know, at the end of the day, let’s face it, somebody’s gotta be able to go throughout their day without, you know, teaching to the point of major, major issues. And so there’s definitely things to be played. I have seen, you know, a little bit of people playing in the waters, is there some type of probiotic topical that I can use to adjust the microbiome? But at the end of the day, right, it’s just like the GI tract, it’s so amazing where, you know, in our stomach, our stomach acid helps to limit the microbial population in our small intestines, so we don’t get SIBO or small intestinal bacterial overgrowth that keeps that pH nice and low. And similarly, on our skin, our skin secretes fatty acids to do the same thing, to keep the pH low so that it’s reducing potential pathogens. And so that basically, these skin microbes are happy and they’re getting what they need out of our skin. And so there’s a lot of opportunity, I think, in the future to really try to understand what our skin is offering to the microbiome to create them being happy and to limit potential pathogens that locally are creating their own inflammatory processes if they take hold. And so I think that’s just another area from a topical perspective that we really, I think there’s a lot of exciting things likely to be coming there.

Patti Devers
Are people putting topical probiotics on their skin, Michael, have you seen that?

Michael Chapman
Yeah, absolutely, I’ve actually used it myself.

Kalea Wattles
I’ve seen it.

Michael Chapman
And not just dirt from the backyard or anything like that.

Patti Devers
Yeah, actual probiotics, yeah.

Kalea Wattles
Well, I was gonna bring that up. I live on a farm, so, and I have small children, and they, I mean, we are always covered in dirt. We’re eating food from the dirt. There’s dirt everywhere. And so I always think we’ve just got, we must have such a robust microbial composition with just dirt everywhere.

Michael Chapman
Well, and just, I mean, one other thing from kind of a nature perspective, get outside, right? What’s the percentage to which you’re outside and encountering actually the sea of microorganisms that we are normally encountering as compared to how much time are we spending indoors in front of our screens, I think is another question that is worthy of research investigation.

Patti Devers
And back to vitamin D, right? And the gut microbiome diversity. So it’s all coming full circle, that’s right.

Kalea Wattles
And Patti, you mentioned quite a few antioxidant nutrients that can be helpful for the skin and inside the gastrointestinal tract as well. But I’m wondering if you’ll share some maybe nutrient insufficiencies or maybe even frank deficiencies that might show up on our skin.

Patti Devers
Yeah, I think the best example, like I said, is omega-3s because of that follicular keratosis that we see. And like I said, when you think about aging skin, you think about wrinkles, you think about sagging skin, selenium comes up a lot because it’s actually even being used to treat some of these things. Vitamin A comes up a lot, vitamin C because it is an antioxidant and prevents aging and aging of your skin. But like I said, some of those other micro-minerals as well. But the one I think is the most obvious that shows up on your skin is the essential fatty acids, the omega-3s. I’m also gonna make a plug for polyphenols too because we know polyphenols are important to feed our microbiome and help with diversity, and they’re also antioxidants. So in general, if you have a lot of oxidative stress, you’re not getting enough antioxidants in your diet, you’re gonna see it everywhere, including skin and aging and wrinkles. And again, like I said, that the rash from the omega-3s, I think, is probably the most obvious that we see. Unless you have a different one, Michael, something else, do you agree?

Michael Chapman
I mean, not specifically, Patti. I think that’s a really good coverage. I would also just make the point too that it’s funny that some of our GI microbes make some of these things for us as well.

Patti Devers
Yeah, yeah.

Michael Chapman
There’s actually a whole host of different vitamins, including some antioxidants that our gut microbiome makes for us by fermenting different food substrates that we’re eating. So, and they’re actually doing the very similar process on the skin as well. And so that’s another way that, you know, Patti, you mentioned before, these antimicrobial peptides, some of which that our own immune system makes, our T-cell makes both in our gut and on, in our skin. But I mean, lo and behold, the microbes that are our commensal microbes are also making the same things because basically, they’re trying to make sure they have the best real estate on the skin, and they’re trying to keep out all of the things that our system would call potential pathogens. You know, whether that’s something like staph. And so we wanna make sure that we’re keeping them happy because they have their own antioxidant capacities to be able to compete, probably even better than we can against some of these neighbors that they don’t find so neighborly.

Patti Devers
Agree. Agree.

Kalea Wattles
Thank you, microbes, for protecting us.

Michael Chapman
Yeah.

Patti Devers
Yeah.

Kalea Wattles
Gratitude towards these little microbes. And on that note, we’ve talked about different microbial compositions, we’ve talked about short-chain fatty acids, we’ve talked about immune markers. So let’s talk testing because I know that that’s your love language over there. So tell us a little bit about, you know, are there certain biomarkers we’re looking for? Are there red-flag microbial patterns that we should be aware of, especially in our patients who have diseases of the skin?

Michael Chapman
Yeah, I mean, I will say, I think before we talk a little bit about GI markers and things of that nature, I would again make, kind of going back to these two core components, inflammation being a major connection between the GI tract and the skin. I do think there’s a place to think about things like an hs-CRP, a sed rate, and things like that to understand our overall inflammatory burden to look at cytokines. But if we’re talking about this GI contribution to the skin, which I think we know is pretty clear, we want to certainly start again with inflammation. And so we’re looking for any signs and symptoms of inflammation in the GI tract. We will look at things like a calpro test, stool calprotectin, which is going to tell us about any type of potential inflammatory bowel condition, that’s really severe levels of inflammation going on to produce a release of this calprotectin biomarker, eosinophil protein X is a marker for IgE-mediated types of responses. And so, as I mentioned before with eczema, right, this is a Th1, Th2 imbalance leading to IgE production. And that’s why you think of IgE, you think of allergies, right? Like seasonal allergies like I have right now where I’m getting itchy eyes and all the annoyances. That’s an IgE process. And so, in the stool, eosinophil protein X is an indicator of that going on in the GI tract. So that, I think, would be super relevant, but it’s not just the inflammation, it’s is that inflammation getting across the gut barrier, right?

We wanna make sure that that gut barrier is intact. And so we look at things like fecal-secretory IgA, which is a marker to show any type of barrier disruption right at that interface between the microbiome and our own gut lining. Is there some type of reactivity where the system’s saying, “Hey, like I don’t like what’s happening, let’s send out the guards and just kind of get rid of all this nonsense,” that’s IgA, and so if I start to see that, I’m gonna say, “Hey, there’s disruption at the barrier.” And the last thing we want if we have a skin patient on with that we’re working with is we want any of those inflammatory particles getting across into the system, right? Because that is one of the things that is going to generate systemic inflammation and contribute to skin issues. So those are major ones. Even something like a stool zonulin, which we’ve, you know, looked at quite a bit and it seems to be another indicator of inflammation in the GI tract. There’s some sort of barrier disruption. Some people look at it with respect to permeability. I tend to think of it as that interface in between inflammation and permeability cause anytime the gut’s inflamed, it’s permeable, right? If you have a leaky gut, you likely have some degree of inflammation going on. And that’s just kind of how those two things are connected to each other, so that’s the main thing, from a stool testing perspective, to look at inflammation.

But then, as I mentioned in some of those conditions before, whether that’s eczema, psoriasis, do you have enough of a microbiome? We saw that low levels of bacteria overall was associated with skin conditions. And so do you need probiotics to support your microbiome? Do you need prebiotics to feed your microbiome so that they can produce those good products that the good bugs in our gut make as compared to some of the negative products like Patti mentioned, LPS, that are inflammatory to the system and inflammatory to the skin to make sure that not only is there no inflammation, but the permeability is nice and sealed up, things aren’t getting into our system causing additional problems on the skin. So I think globally, just to recap, that looking at inflammation in the GI tract, looking at inflammation systemically, and making sure that you don’t have a permeable gut are probably great places to start there.

Patti Devers
Can I add one or two things to that, Michael? All of that a 1,000% agree. Making a plug again for fecal calprotectin, which is obvious, that’s an obvious one. But we also see various patterns on stool testing that might make us think about SIBO. And with SIBO, you can have maldigestion and malabsorption of a lot of really important nutrients that can also feed the skin. And within whole genome sequencing, there’s an ability to look at the microbiome’s potential to make some really important metabolites. And some of those are, like Michael just said, hexa, LPS, or TMA, trimethylamine. We think about trimethylamine, interestingly, as you know, it’s made by the bacteria. It gets into your systemic circulation, it goes to liver, it gets oxidized, becomes TMA and a cardiovascular risk factor. But TMA can also affect your skin and mix. If it’s not present, it can actually make the cells pretty fragile and cause further breakdown and further skin lesions. So like Michael was saying, there’s a lot of things you can measure within the gut, and it all basically has to do with the gut’s ability to potentially make these inflammatory mediators or actually directly measuring these inflammatory mediators, like Michael just pointed out.

Kalea Wattles
There’s so much juicy information to be obtained here. And I’m grateful for the opportunity to take a look into the gut because, you know, sometimes I’ll hear my colleagues say in regards to something like a salivary cortisol, they’ll say, “I can kind of predict what my patient’s pattern will be. But with the gut, I have never been able to predict accurately what is going on in there without looking,” cause like you’ve highlighted, there’s so many components and so many variables that I just have not, I don’t have a mental algorithm for that yet.

Michael Chapman
It’s a complex system, and complex systems are probably impossible for our brains to comprehend. But I’ll say something interesting on that is because there are so many things going on, we, we started to look not just at, is this bacteria here, I mentioned Akkermansia earlier, and that’s an example. Sometimes we can say, “Is this bug here or is it not?” But really with the invention of, like, machine learning and things like that, that we can start to break apart patterns to say, “You know, this collection of bacteria make these good products or this collection of bacteria together, when they’re overabundant, they make these bad products.” And so we’re starting to get more into this idea of the microbiome as a pattern analysis. And so that’s another thing that we can sometimes use as part of the evaluation to say not just, you know, is, do we have enough lactobacillus? But we can say, “Wow, this microbiome pattern is actually much more likely to be producing inflammatory compounds as compared to this other microbiome pattern that’s more likely to be producing butyrate and all the things we really like.” So we’re getting there from a perspective, but to your point, yeah, it is one of those things where you have to look at every single thing. And we didn’t even mention like the gut-brain connection, which is a whole other podcast, right? So, there’s so many components, absolutely.

Patti Devers
I think what’s fascinating is because Michael and I, and here in our department, we’ve been diving deep into metagenomics and whole genome sequencing, and it really has shifted our thinking and our, they changed how we really look at the microbiome. Because from our perspective, correct me if I’m wrong, Michael, it’s no longer just, what’s your laundry list of bacteria and how high are those levels? To Michael’s point, it’s how are they moving together? What is the stuff that they’re making? Let’s look at the metabolites. Look at their potential to make other metabolites. So it’s not necessarily the laundry list of who’s here, it’s what are they doing, how are they moving together, and what’s happening? That’s been a big shift for us here to really change how we think about the microbiome as not just a laundry list of bacteria.

Michael Chapman
Yeah, agreed.

Patti Devers
Mm.

Kalea Wattles
It reminds me of how we think about body systems. Like in functional medicine, we think about all the body systems individually, and then how they’re all influencing each other. So it’s kind of the matrix of bacteria. And this is making me wonder, so you’re kind of creating these microbial imbalance patterns and, of course, we avoid protocolizing, we’re always gonna give precision personalized medicine. But does the identification of those patterns help you to develop more specific treatment plans if we see a certain pattern? Are there treatments that might work more efficiently than, you know, we knew before?

Patti Devers
Yeah.

Michael Chapman
I didn’t think of it more as actually having earlier indicators of dysfunction.

Patti Devers
Hmm.

Michael Chapman
And certainly, because at the end of the day, I think, Kalea, like what we’ll see again as we keep coming back to do the root cause medicine, right? Like, what about this person? Whether it’s something in their diet, their lifestyle, their mental stress strategies, all those types of things are contributing to all of those dominoes starting to fall. And I think having that pattern analysis is where we’re starting to go, is we actually… We’re wondering, is the microbiome that is shifting first, and then you start to see the downstream consequences later, right? It, inflammatory bowel disease is not likely something that just occurs haphazardly and overnight. It’s probably a process that developed a long time, but yet our tools that we currently have for diagnosis and conventional medicine is really late in the game. And we find that with a lot of our chronic diseases, whether that’s something like a blood glucose that’s a really late in the game indicator for metabolic dysfunction. And so similarly, I think what the pattern analysis will show us is ultimately, we can get to the dysfunction occurring from a functional perspective a lot earlier so that we can actually inform our patients and educate, docere, to get to what their actual core components that need to be changed and why, so that we’re not getting them all the way to inflammatory bowel disease. We’re correcting them earlier.

Patti Devers
The other thing that stuck out, I think, Dr. Wattles, you mentioned this, is that, so you talk about salivary cortisol, Michael, you mentioned the gut-brain axis. If we know that there are all different kinds of axes, and to your point, Dr. Wattles, these are systems that are all working together. So if we know that there’s a bidirectional axis between your gut and your brain and that your brain can influence the microbiome, there’s actually a gut-brain-skin connection, right? Stress that can change your microbiome, that change in your microbiome can also affect your skin. Corticotropin-releasing hormone from your brain can actually directly affect the tight junctions within your GI tract, causing further leaky gut or intestinal permeability. So it is all these systems that are really working together. And to Michael’s point, as we use machine learning and AI and we start to dive deeper into the microbiome, we’re seeing how all of these things start to shift together. And we’re looking for various patterns to really hone in on very specific different treatments for a patient rather than a probiotic. Could be stress management, could be a lot of different things. So we’re really looking at all of those patterns and trying to really push this whole field forward.

Michael Chapman
I gotta jump in there cause I got a little in the game here. Because I have also looked into this, it’s amazing that one of the things that we see with stress and chronic stress is that actually, our catecholamine production, you know, our epinephrine and our norepinephrine will actually change the dynamics of what our skin is releasing. And because that quality of the fats and what our skin is producing on the surface level, that actually changes the skin microbiome. So stress directly can alter your skin microbiome. And particularly, some of the things that, you know, we have a lot more fungus yeast on our skin as compared to in our GI tract. And so they tend to really take advantage of the stress component, the stress factor changes that happen. And actually, when I was in rotations at Bastyr University, so we actually did biofeedback with people with eczema, and we saw that actually, there’s plenty of literature to suggest that stress reduction techniques, mindfulness techniques, biofeedback, heart rate variability training, breath work training, these things actually have tremendous utility in skin conditions because of that rebalancing of the sympathetic parasympathetic system actually changes your skin microbiome. Like it’s just, it’s so fascinating.

Patti Devers
Gut-brain-skin axis, and that all works together. So to your point, Dr. Wattles, you know, depending on what you’re seeing in these patterns, it may not be a probiotic or fiber, it could be biofeedback, to Michael’s point, and stress reduction, yeah.

Kalea Wattles
What a powerful example of a whole person health care. Like, wow, this is profound.

Patti Devers
Yeah.

Kalea Wattles
Now I have to ask this question before we move on and close our episode today. Let’s say we do the testing, and Michael, just like you said, the resolution of some of these conditions might depend on the severity or the chronicity that was there in the first place. When should we do a repeat test?

Michael Chapman
Yeah, we get this question a lot. That’s very common. I tend to think that it, really, that it does depend, but the thing that it depends on is how significant was your therapy, right? Did you really change things dramatically? Because the more dramatic of a change that you make, I think the sooner you want to test and say, “Okay, it is making the improvements that I was wanting to make.” Certainly, if somebody’s got something that is more of a red-flag marker, like a calprotectin that can indicate inflammatory bowel disease, that’s something that needs to be checked in like three to six weeks just to make sure that you’re following the due diligence protocols on that. But for other things, you know, we tend to think of three to six months for repeat testing. Again, if you want to do it sooner to make sure you’re on the right track, that’s certainly a possibility. If it’s more of like a long-term maintenance, I’m just checking in on an annual type of thing, other clinicians will use it that way too. And, of course, there’s the factor of how often is your patient going to be willing to do a stool collection.

Kalea Wattles

True. It’s not glamorous, but it is helpful.

Patti Devers
Yeah.

Kalea Wattles
As we come to a close today, I wanted to extend an invitation to share whatever important takeaway you hope our listeners will leave this episode knowing.

Patti Devers
Well, I can start, Michael. I think it’s… I think the importance of the microbiome, we’re just in our infancy as it relates to understanding how important this is. All the signals that are happening, gut-skin, gut-brain, gut-lung, I mean, it’s all there. So, again, we’re in our infancy. It’s not as simple as here’s a fiber and a probiotic and now you got a healthy gut. This is far-reaching effects that, again, we’re scratching the surface. I mean, this is a fun exercise for us to discuss gut-skin cause it’s not well understood nor discussed. The gut-brain-skin connection, as we put the systems together, I think as you pointed out, Dr. Wattles, is fascinating, but just to know that the microbiome is complex and everyone thinks they’re understanding it, but we’re in our infancy and getting there to see how far-reaching these effects are.

Michael Chapman
Yeah, and I think the thing that I would want people to kind of take away is knowing how complex these interactions are. The reassuring thing is at their roots, we’re talking about systems that we’re actually really familiar with. We’re talking about inflammation, we’re talking about dietary impacts. You know, when it comes to acne, one of the biggest things that we see is like high-glycemic loads tend to be a dramatic producer of the changes that occur with acne. And so, at the end of the day, you get back to these basic fundamentals. And so to me, that I think that is something to take away is like, yes, it’s a complicated system, but actually, we know we have the tools to know how to address inflammation. We have the tools to know how to address dietary production of inflammation. You know, removing obstacles to cure, reducing overall toxicity, improving our antioxidant status with what people are eating, removing the toxins from their environment and their drinking water, and things like this. So, at the end of it… At the end of the complexity, we actually already know how to deal with this. We just have to make sure that we’re implementing, and we have to make sure that our patients understand the importance of it so that they feel compelled to do it. And I think that is what I would… I think it’s just so reassuring that, you know, as complex as something gets, we still already have the key. And I just like, I think that’s the thing, yep.

Kalea Wattles
I felt a sense of relief as you said that. Thank you for that reassurance. I wanted to thank you both so much for sharing your insights today. I know you have a long history of podcasting together, so thanks for bringing me into your circle today. It’s just been a pleasure to chat with you, and we look forward to being with you at the Genova Diagnostics Pre-Conference at AIC this year with Drs. Jeff Bland and Mark Hyman. What a fun experience. We’ll see you at AIC, thanks.

Patti Devers
It’s an honor, thank you.

Kalea Wattles
Discover the latest research and innovative clinical practices at IFM’s Annual International Conference, May 29–June 1, 2024, at the Bellagio in Las Vegas. For more information, visit aic.ifm.org.