Skin Aging Treatment and Skin Microbiome: What “Leaky Skin” Could Be Telling You About Inflammation, Hormones, and Healthy Aging | Kiran Krishnan

0:00Barrier dysfunction in the skin is an independent risk factor for Alzheimer's and dementia. They're showing that it's more associated with barrier dysfunction on the face rather than, say, the arms and the legs. And probably the part of the skin, especially women, irritate the most because of all the things that they do. I want to talk about that Baltimore study and what we learned about skin aging and inflammation in the body. What was fascinating about it is they found that aged skin was one of the best predictors for mortality and morbidity in individuals. Karen Krishnan is one of the most influential voices in microbiome science.

0:37Known for translating cutting-edge research into real-world results. A research microbiologist and leader in microbiome therapeutics. He's uncovering the hidden link between gut health and leaky skin. And why it may be the missing piece in anti-aging. How do I know if I have leaky skin? What are the signs and symptoms they could look for? If you're seeing a lot of hyperpigmentation on your skin, the hyperpigmentation is an example of senescence. Senescence is where cells become zombie cells, essentially. If aged skin is increasing your risk of death, what is the worst thing women are doing to their skin on a daily basis?

1:15All this of the skin is probably causing more harm than good. So good, so good, so good. New summer arrivals are at Nordstrom Rack stores now. Get ready to save big with up to 60 % off brands like Rag & Bone, Levi's, Adidas, and Free People. Join the Nordi Club to unlock exclusive discounts, shop new arrivals first, and more. Plus, buy online and pick up at your favorite rack store for free. Great brands, great prices. That's why you rack. This episode is brought to you by Google Chrome. You think you know a browser, but Gemini and Chrome, that's new. It can help you with practically anything on the web, like restoring a vintage motorcycle from a 50-page restoration block, or finally break down that long article you've had open for weeks.

2:03Gemini and Chrome is here for it. Ready to make anything online make sense? There's no place like Chrome. Check responses set up required, compatibility and availability varies 18+. What is the biggest lie women are told about skincare? Well, I think one of the biggest things is that your skin is going to age, right? Wait, are you saying it's never going to age? Well, you can dramatically slow down the age. Okay, okay. Because I was like, I'm all in if you say never. I wish never. But the thing is that the formation of fine lines, wrinkles, dryness, hyperpigmentation, and all that is inevitable, right?

2:41They're associated with an aging process and that the way to overcome them is by masking them with more things, right? So fillers and Botox and all of that, that that's the only way you can do it or covering it up, right? And so, to me, there's this, hopefully, we can lead a little bit of a mind shift where making skin look better by making it healthier rather than simply the act of trying to make it better looking, right? And so, because we can make skin look good, there's many different tactics to it, makeup and surgery and all of that. But are we actually making it healthier? And the funny thing is we don't do that with any other organs in our system, right?

3:26Yeah. We don't mask dysfunction in the organs just to try to make the organ look better. But the skin is an organ, and we forget that, and we forget its role as a barrier. And so we kind of skip over all of those important features of it, and then we just want to make it better, like a veneer, if you will. And so I think one of the misconceptions and one of the lies is that you cannot improve your skin without all of those procedures and tactics and so on. You know, I think you can. I think there's more natural ways that you can do that. Okay, we're going to get into those today. But we want to talk about that Baltimore study and what we learned about skin aging and inflammation in the body.

4:09What was fascinating about it is they found that aged skin was one of the best predictors for mortality and morbidity in individuals. Right now, in our world, we would normally and if you said this to me eight years ago, nine years ago, I'd go, well, that makes sense because the skin is a reflection of the inside. Right. So their skin is aged because they're unhealthy on the inside. So, yes, they're going to be more sick. They found that. No, that's not actually true. In fact, the aged skin precedes any biomarkers that they could find on the inside that would lead to any disease pathology. And so the skin dysfunction started first.

4:46Now they were able to correlate also then skin dysfunction with very specific conditions like bone health, right? Like who would have thought your skin has an impact on bone health? Well, I mean, we generate vitamin D there. So that shouldn't have been a total leap, but it is much deeper than that. I know my listeners are savvy and going to be like, oh, vitamin D, but it actually goes way beyond that. It's about the actual function and barrier of the skin being compromised. Yeah, it's the barrier of the skin being compromised, thereby allowing in pro-inflammatory, you know, antigens and mediators and toxins and all that to actually get into the skin past the stratum corneum, which is a very top, closer to the dermal layer.

5:26So if the audience isn't familiar, you've got the stratum corneum at the very top, you've got the epidermal layer, and then the dermal layer, right? So the skin has these multiple layers. The immune system functions in both the epidermal and the dermal layer. And so if things penetrate far enough into the layer of the skin, it's going to elicit an immune response. Because the skin acting as a barrier shouldn't see those antigens in there. And so when things penetrate far enough, they can elicit enough of an immune response starting in the skin that actually then spreads throughout the rest of the body.

5:59And in fact, like, for example, psoriasis, this is a perfect example, right? In a psoriatic lesion, there are immune responses that are occurring. So the immune system is attacking your own parts of your skin. There are these proteins that are being generated in these psoriatic lesions that are very specific to a psoriatic lesion. We find those same proteins in bone where there's inflammation that's starting the process of osteoporosis. Right. So there's a real connection here between inflammation starting at the surface and then penetrating throughout the rest of the body and perhaps proteins and other components of the inflammation from the skin traveling throughout the body and eliciting more inflammatory responses elsewhere.

6:45Right. So then what the study concluded was aged skin was an independent risk factor for morbidity and mortality, looking at age related chronic conditions. Independent outside of obesity and everything else. Right. It's on its own. It's an independent risk factor. So if aged skin is increasing your risk of death, what is the worst thing women are doing to their skin on a daily basis? So if you think about all the sterilizing of the skin, right, so we wash our skin with all of these antimicrobial soaps and, you know, benzoyl peroxides and all that. So we're pulling off the layer of microbes, protective microbes of our skin, thereby and then also, you know, removing the top layer because a lot of people do, you know, exfoliation and all of these things.

7:36So we're like peeling off the top layers of the skin and then putting on toxigenic compounds on top of it. Right. That have all kinds of benzo, like, you know, they have plastics, microplastics in it, pesticides, herbicides, you know, all of these chemicals that you find that are found within personal care products that all can be toxigenic, damaging to the skin, drying out the skin. And we also don't know what things like microneedling and all actually do to the skin eventually, right? Because we're penetrating those barrier systems. And I had a great conversation with a plastic surgeon that is starting to become more skin microbiome conscious.

8:16Yeah. And she was starting to get really nervous about all of the microneedling and injections and all that they do because it's really unusual to do that much damage, right? It's completely unnatural to be doing that much damage, that depth of the skin. And maybe a little bit of microneedling at like 0.25 millimeters or something like that would be just okay, right? We have hair loss studies and all that on that. But the depth that they're going into, I think, is probably causing more harm than good because you're breaking that barrier quite significantly. Well, you're breaking that barrier significantly.

8:48And then it's also no one talks about the other products being used around it when the barrier gets compromised in that way. Right. We can hypothesize that they likely damage it. What I want to ask you is that you're really trying to shift the paradigm away from you just have damaged or aging skin and talking more about the phenomenon of leaky skin. Can you tell us more about that? We mentioned skin is a barrier, right? That's one of its primary roles. It's, in fact, one of the largest barriers in your body. You come to realize is that any part of the body that's a barrier that starts to become dysfunctional, meaning it starts becoming more permeable than it should, leads to complications and disease.

9:29There's been this really well thought through and proven concept called the atopic march, right? So this is kids with eczema and psoriasis, especially eczema or some form of dermatitis, tend to have a barrier dysfunction in their skin. As a result of that, food and environmental antigens actually leak through the skin and the immune system meets those antigens in the periphery. As a result of that, you lose all of the ability of developing oral tolerance to them. So they develop hypersensitivity to all of these antigens, right? So a kid who has dermatitis, who's born with dermatitis, has an eight-fold higher risk of developing severe allergies against food particles, environmental particles, and so on.

10:16That's called the atopic march. And dermatologists have known about it for some time. There's a few groups that are working on solutions for the atopic march. So we've known that the skin as a barrier can become compromised. Things can actually leak through. And when they leak through, they're entering into our system in a place where they shouldn't be. And the immune system does not like that and it freaks out. Right. So anytime the skin barrier becomes compromised, I think we start to see a number of issues that develop. Well, what's interesting is that as we've begun to understand this connection of actually developing allergies via the skin barrier, We've seen the shift in pediatricians recommending that we delay food, right?

10:56If you can define oral tolerance that you had mentioned earlier. So oral tolerance is this beautiful magical system where when you sample, say, food, let's take a peanut antigen, right? When you sample it through your digestive tract, there are mechanisms involved in your digestive tract lining that allows your immune system to sample these antigens and then get cues from the microbiome that this is fine. And then it upregulates a part of your immune system called the Treg system. That Treg system suppresses any unwanted immune responses against it, right? So to get more technical about it, you've got this antigen that comes in.

11:35The microbiome, if you have a healthy microbiome, is producing things like short-chain fatty acids, inducing more IgA, immunoglobulin A, which can bind to these antigens and kind of neutralize them and kind of mask them as, hey, this is not a problem, right? Then you've got these immune cells called dendritic cells that reach across the lining of the gut. They sample all these things that are in the mucus layer. When they sample something in the context of short-chain fatty acids and IgA, they upregulate a type of T cell called a Treg cell. That Treg cell builds memory and tells the rest of the immune system, don't attack this thing.

12:13That's called oral tolerance. So this is how we're supposed to encounter most antigens, certainly food-based antigens. Because the skin is supposed to be a barrier. Antigens just land and brush off of it, right? But we inhale things every day. Things go through our eyes, and that's why our eyes, our nose, our ears all drain into the back of our throat, right? And we swallow all of those components. And so we sample it through the gut. That is sampling for oral tolerance. We don't have those same Treg cells. We don't have those same dendritic cells in our periphery. So when a food-based antigen enters through the skin and enters in the peripheral area, it activates an innate immune response like natural killer cells, basophils, isonophils, all of these really freaking out panicked immune cells that are seeing something it shouldn't see in a location that it shouldn't be in.

13:05And so they elicit a hypersensitivity, very inflammatory response to it. And so you lose that learning from the Treg cells. Now, this process is so important that the Nobel Prize in 2025 for physiology and medicine was given to three scientists that discovered this whole oral tolerance Treg mechanism. You know, and so when they're doing those studies and they're trying to look at if we put an antigen on the skin of an animal, Can we see antibody responses inside the animal against those antigens? That's what they were trying to figure out. Yeah. And for people listening, this is when medicine realized that all of the recommendations of delay peanuts, delay eggs, all of that was actually creating food allergies in children rather than actually preventing them.

13:54So, I mean, Nobel Prize, of course. This is like a really big phenomenon because generations were impacted by that. And that's why I think it's so important in the context of this conversation. What I want to ask you, if people listening right now, they're wondering, how do I know if I have leaky skin? How do I know if I have barrier dysfunction on my skin? What are the signs and symptoms they could look for? So you wash your skin, let's say with regular soap, and let's say you don't put lotion on it. If your natural skin tends to be quite dry and what we call thin skin, if you're developing a lot of fine lines and wrinkles prior to the age you think you should be.

14:30Yeah. So if you're in your late 20s, early 30s and already developing fine lines and wrinkles, if you're seeing a lot of hyperpigmentation on your skin, the hyperpigmentation is a example of senescence that's on your skin. Right. Senescence is where cells become zombie cells, essentially. So your melanocytes that are producing the melanin are undergoing a lot of oxidative stress and damage. And as a result of that, they're kind of becoming dysfunctional and becoming zombie cells and just sitting there and producing melanin. And so that's a sign that there is a significant amount of damage occurring in the skin.

15:04They used to call those age spots for a reason. It's because usually with age comes these dysfunctions. But now you're seeing it in younger and younger individuals. So the condition of your skin will tell you whether or not it's leaky. The most common one is dryness and flakiness in the skin. So if your skin is, now if it's been like that all your life, there's some people that just have really low oil production and a poor ceramide layer, right? So their skin has been dry their entire life. That's a little bit different than let's say you're in your 20s, 30s, 40s, and you're noticing that your skin is getting drier and drier and it's harder to keep moisture on your skin.

15:44And of course, we're using topical lotions and things that kind of mask it. They don't really moisturize the skin in the way we think they do. One thing I hear from women all the time is that they're struggling with symptoms like hot flashes, sleep disruptions and brain fog, but aren't sure where to turn to for help. Menopause is inevitable, but suffering through it isn't. That's why I want to tell you about Alloy. Alloy is a digital health platform that connects you with a menopause-specialized doctor who can create a personalized treatment plan tailored to your needs, all from the comfort of your home.

16:19Join the 95 % of women who tried Alloy and saw relief in the first two weeks. head to myalloy.com and use the code DRBRYTEN. That's myalloy.com, M-Y-A-L-L-O-Y.com and the code DRBRYTEN, D-R-B-R-I-G-H-T-E-N. Share your symptoms and you'll get a fully customized treatment plan and unlimited messaging with your doctor. Plus, you'll get$20 off your first order today. That's M-Y-A-L-L-O-Y dot com, code Dr. Brighton. But if you're doing all of those things just to maintain some degree of moisture in your skin, and you're losing moisture very fast, it's likely becoming leaky. One of the ways in which we test for leaky skin is something called TWEEL, T-E-W-L, Trans Epidermal Water Loss.

17:21It's a device that actually measures how much water your skin loses. And that is a really strong surrogate marker for skin barrier function. Right. So looking at that dryness is really important. Yeah. If topical lotions are not hydrating our skin, what actually does? Yeah. So that's a great question. Right. So I'm actually in the process of trying to develop a moisturizer that will actually help. I'm going to make it. I'm going to make that thing. Right. Here's why, because most topical lotions are water-based systems, they're emulsions, right? And the way the skin is designed is things aren't supposed to penetrate through from the outside in, nor is moisture supposed to penetrate out from the inside out.

18:03How do we prevent moisture from penetrating out? Well, we have this fatty acid mortar layer called the ceramide layer, right? The ceramide layer binds all the cells, the skin cells together. So you've got this hydrophobic layer that's acting as a barrier. that prevents evaporative moisture, losing moisture through evaporation. So then the moisture can't come out of the skin. Now, if your skin is getting dry really easily, it means that ceramide layer is broken, right? And it's getting dry because evaporation is drying out your skin easily. So when you put lotion on, which is a water-based system most of the time with an emulsion in it, you're actually not getting any sort of barrier fix because the lotion is temporarily preventing that water loss.

18:48That's why your skin feels a little more moisturized, right? Because it's acting as a cap to preventing the moisture loss. But then once the moisture in the lotion evaporates, it goes back to feeling dry again, right? And so one of the best things you can do, actually, so if you're able to use lipids on the skin, that's much better, right? Lipids will penetrate a little bit further in and will help hold moisture in better. so we're trying to work on and develop an anhydrous lotion which means a lotion with no water in it but it also can't be a thick enough liquid that occludes your pores and creates comedones which just creates lesions and all that so it has to be thin skin mimetic lipid right there's not anything out there right now so people just have to use the lotions that they have and maybe use some oils or things like that from time to time.

19:37The other thing you can do is actually improve your liver health and take in enough phytoceramides, right? So certain fibers, so bran, rice bran and other fibers, so rye and things like that, have these compounds in it called phytoceramides that your liver will convert to the type of ceramides that you have in your skin, and it'll transport it to the skin to replace the ceramides that you're missing, right? So most people wouldn't connect their liver health with their skin health, but it plays a really important role, right? So if you're naturally really dry, make sure your liver is healthy. Take your turmeric, your milk thistles, your dandelion roots and all that to make sure your liver is healthy and get enough of the phytoceramides into your diet.

20:24You just mentioned gluten-containing products. Are there ways to get those phytoceramides that are not gluten-containing foods? Yeah, you can get it from rice as well. Yeah, brown rice has phytoceramides in it as well. Perfect. And if you're not gluten intolerant, you can have it from time to time and get the ceramides in there. But the liver plays such an important role in that, right? So the liver can also take fatty acids from the diet and produce ceramides out of it. And so if you're getting, as long as your liver is healthy, you'll still start producing enough ceramides to replace the skin, what you're losing on the skin.

20:58And when you say fatty acids, what kind are you talking about specifically? So normally like lipids from things like olive oil and so on. This is one of the reasons why olive oil tends to be really good for the skin. So having a good measure of omega-3s, omega-6, they can be actually metabolized and reconstructed into ceramides for the skin. Which for people listening, omega-3 fatty acids, it's also been found people have higher omega-3 content when they're measured in their blood, have lower levels of IGF-1 contributing to acne. So you see that correlation. So you get a two for one. You get two for one.

21:34The inflammation goes down and so on as well. Yeah. Let me ask you, why do women tend to have more skin barrier dysfunction than men? Well, I think in part because women actually treat their skin a lot more with a lot more things. How many? It's like 13 products a day, right? Exactly. Is there anything more to it or is it just like how much we have been influenced to treat our skin? I think hormones play a big role as well, right? So hormones have a dramatic effect on the skin as they do with everything else in the body. So women have that unfortunate side of having more complications with hormone imbalance than men do.

22:11Yeah. Okay, we're going to talk hormones, everyone. So just hang tight. But I want to ask you, what about these influencer like 13-step night routines or wearing masks overnight? Some things are hyaluronic. Sometimes they're like Korean glass skin. I don't even know what's in that. But what are your thoughts about what that's doing to the skin barrier and also the microbiome? Yeah, I think it's so unnatural to have that on your skin for that long a period of time, right? I don't think people need to sterilize their skin. Now, if you're dealing with really bad cystic acne or something and you're on a procedure or you're on a protocol for cleaning your skin, benzoyl peroxides or whatever, maybe that's a different thing.

22:47But normal day-to-day routines, I don't think you need to sterilize your skin, right? So maybe a light soap, maybe to get some of the dirt off, and then hopefully a skin mimetic moisturizer. What is skin mimetic for people listening? So skin mimetic means it mimics the type of oils that are produced on the skin. So they're normally very thin, high-penetrating oils, right? So like glycerol caprolate is a good one, or caprylic acid is another good one. so if you find like a moisturizer that is based on glycerol caprolate or caprylic acid they tend to be much more skin mimetic they're thin they don't occlude they don't create comedones which are the lesions and and they're just really healthy for your skin in that in that format so light moisturizer light cleaning sleep right that's it and then how about in the morning Same thing, I would say.

23:42Because I have seen, I got to say, there's like the Korean skincare routine, the Japanese, these Asian women are like, you wake up in the morning and it's just cold water on your face. I would say nine out of 10 times I don't actually wash my face in the morning. It's cold water and just regular water. Seriously. Every time I have a skin expert on or like a dermatologist, they will talk about how they don't wash so much. Everything where we've hypersterilized components of our body, our home, everything, right, where we've warded off microbes, we start to see dysfunction occurring. Because what we forget is microbes play such an important role in every aspect of our health, including our skin, right?

24:23There's so many functions on our skin that we cannot do ourselves. For example, I'll just give a quick example of that. It's really important to maintain a very narrow pH range on your skin, right? You want your skin to be slightly acidic. It's around 4 to 4.5-ish. It can be a little bit lower than that. But the main reason you don't want it to be more neutral or even basic is because you'll get fungal overgrowth on your skin all the time, right? There are moles, spores, and all that all over the place. They settle on our skin. They will easily grow if our pH was any higher. The way we maintain pH on our skin is we have beneficial microbes on our skin that break down the oils and take out the fatty acids.

25:05And they make fatty acids from the oils that are being secreted, and those fatty acids lower the pH of the skin. So something so foundational to the structure and function and look and barrier function of our skin, microbes do that for us. If we knock those microbes down consistently and their numbers are not where they should be, we lose pH balance in our skin. Then you see all these products about pH balance, pH balance, and you need to use products to balance your pH on the skin, right? So it's just an elegant example of how nature just in this symbiogenic way, we've got this beautiful relationship with these resident microbes on the skin maintain the healthy terrain by controlling the pH.

25:51Same thing in the gut. Let's talk about the role hormones are playing in skin barrier dysfunction. Yeah. So, I mean, I think most people understand that hormones have an impact on the skin, right? So, we see hormonal acne, for example. You know, we see topical, skin topical hormone use, which is awesome, right? And we know that estrogen has a very positive impact on the skin. We talked about, we mentioned the pregnancy glow earlier on, you know, before we got on. And that's a hormone-related function of the skin, where you're looking, you have a glow to your skin, you moisturize, skin looks plumper, fewer fine lines and wrinkles.

26:33So we know that an improvement or balance hormones has a very positive effect on the skin. An imbalanced hormone profile has a detrimental effect to the skin. can be very inflammatory, can drive dryness, fine lines, wrinkles, which is another indication of aged skin, right? And significantly, aged skin, especially before the time you would expect, is correlated with drastic hormone dysfunctions, right? So, when you looked at conditions like PCOS and all that that are very inflammatory, those conditions have a direct inflammatory impact on the skin as well. So let me ask you, because with PCOS, there is a large portion of women who will develop cystic acne.

27:17They have inflamed skin. There is going to be skin barrier dysfunction. I have yet to see a study. I don't think it exists. If PCOS is leading to skin dysfunction, is the skin dysfunction maybe contributing further to the inflammation that's associated with PCOS? I think that's a great connection, right? Because I think that's a cyclical effect. And PCOS is pro-inflammatory profile, leading to cystic acne and other, you know, lesion generating issues, right? All of that is directly related to how inflammation from the gut, and PCOS has a big metabolic component, a big gut component to it, right?