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RHR: Understanding the Gut-Brain-Skin Axis


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In this episode of Revolution Health Radio, Chris reviews research supporting the gut–brain–skin axis, explains the ways these three systems are interrelated, and suggests what you can do to improve your gut, brain, and skin health.

In this episode, we discuss:
  • How researchers as far back as 1930 suspected a link between gut, brain, and skin health, and modern research has confirmed this relationship 
  • The relationship between the gut microbiome and cognitive function, memory, depression, and anxiety, and how stress can cause inflammatory reactions in the gut 
  • The associations between gut disorders and skin conditions and how altered gut function impacts the skin 
  • How your skin is both a major target of stress responses and a source for inflammation factors that can cause behavioral and depressive symptoms 
  • Tips for how to improve your gut, brain, and skin health
Show notes:
Hey, everybody, Chris Kresser here. Welcome to another episode of Revolution Health Radio. Two of three Americans will struggle with cognitive decline by age 70. Half of U.S. adults die with a dementia diagnosis. A quarter of a billion people worldwide suffer from depression. Irritable bowel syndrome [(IBS)] is the second leading cause of missing work behind the common cold. Seventy million Americans are affected by one or more digestive disorders. And one in four Americans suffer from a skin condition like eczema, rosacea, or psoriasis. You might be thinking, what do these conditions have to do with one another? On the surface, they seem unrelated. But in fact, we now know that there’s a strong connection between the gut, the brain, and the skin. Researchers call this the gut–brain–skin axis because of the bidirectional connections between these organ systems. Unfortunately, most clinicians and the general public are unaware of these relationships. If you have a skin problem, for example, and go to the dermatologist, they’re rarely going to ask you about your gut health or your stress levels or do anything to address them. The same is true if you have a mental health or mood disorder and you go to a psychiatrist or psychologist. But I can tell you from both research and my clinical experience that when a skin or brain-related issue is present, there is [also] almost always a gut issue. These conditions cluster together. Maybe that’s even true for you. This is important to recognize because if the gut issues aren’t addressed, then the skin problems or mood or cognitive issues won’t fully resolve. Put another way, gut issues are often the root cause of skin- and brain-related problems. And as you know, a core principle of Functional Medicine is to address the root cause of a condition whenever possible. In this episode, I’m going to review the research supporting the gut–brain–skin axis, explain how these systems are interrelated, and give you some tips for how to improve your gut–brain–skin health if you struggle with a cognitive or mood issue, a digestive issue, a skin issue, or some combination of all of them. Ready? Let’s dive in.

Research Supporting the Gut–Brain–Skin Axis

The link between gut, brain, and skin health has been around for hundreds, if not thousands, of years. More than 2000 years ago, Hippocrates famously said, “All disease begins in the gut.” In the 1860s, the German physician Hermann Senator raised the notion that systemic disease, including mental health disorders, are rooted in intestinal self-infective processes, which he called autointoxication. Then, in the early 1900s, the Russian Nobel Prize-winning microbiologist Ilya Mechnikov gained fame for early research suggesting that orally consumed lactic acid bacteria, which we now call probiotics, could reverse problems associated with autointoxication. Two of the most visionary pioneers in this field were John Stokes and Donald Pillsbury at Duke Medical School. They presented a unified theory of the gut–brain–skin axis in 1930, almost 100 years ago. They connected emotional states like anxiety and depression to changes in the gut flora, which they theorized promotes local and systemic inflammation. They observed “an important linkage with cutaneous outbreaks of erythema, urticaria, and dermatitis, by way of physiology and bacteriology of the gastrointestinal tract.” They cited research suggesting that 40 percent of people with acne had low stomach acid, and this suggested stress-induced changes in the gut flora, which increased the likelihood of intestinal permeability, which in turn causes local and systemic inflammation. In other words, these guys were talking about gut dysbiosis, small intestinal bacterial overgrowth (SIBO), and leaky gut as drivers of mental health and skin issues more than 70 years before the connection was recognized, or re-recognized, I should say, in modern medicine. For various reasons, the theories of Mechnikov and Stokes and Pillsbury fell out of favor for several decades. This was partly because they were hijacked by charlatans advocating crazy cures like removing sections of the intestines or taking purgatives, etc. Until very recently, these theories were considered taboo and were ridiculed by the medical establishment. For example, in 2002, at an annual dermatology conference, Stokes’ teachings were described as nonsense, and it was suggested that they should be swept into the dustbin of history. But today, these discredited theories are actually at the cutting edge of science, and the hypotheses of early pioneers like Mechnikov and Stokes and Pillsbury have been confirmed by modern research. Entirely new areas of study have emerged like psychodermatology, which is the study of the relationship between mental health and skin health, neurodermatology, [which is the study of] the connection between neurological health and skin health, and psychoneuroimmunology, which studies the interaction between our psychology and our nervous and immune systems. I want to talk a little bit more about what we’ve learned about the gut–brain–skin axis in the last 20 to 30 years. The gut–brain connection is deeply rooted in our language, of course. We have sayings like, “I have a gut feeling,” or “I have butterflies in my stomach.” Way back in 1933, two physicians working at the New York Psychiatric Institute wrote an article in a journal called Psychiatric Quarterly and said, “We feel justified in recognizing the existence of cases of mental disorders which have, as a basic ideological factor, a toxic condition arising in the gastrointestinal tract.” That [quote] was from Armando Ferraro and Joseph Kilman back in 1933. At the end of the paper, they said, “These problems will require time and we hope to be in a position to report on them in the future.” Unfortunately, their wish remained unfulfilled for almost 70 years. Their words were almost completely forgotten until the turn of the 21st century. But over the last 10 years, epidemiological research has rediscovered this connection between the gut and the brain.

The Gut–Brain Axis

For example, 60 percent of patients with functional gut disorders like IBS have anxiety or depression. Until recently, researchers wondered if the gut was causing brain issues or vice versa. But we now know that communication between the gut and the brain is bidirectional. Stress and anxiety can affect the gut in several ways, as I’m sure many of you listening to this have experienced firsthand, and gut dysfunction can affect the brain and the central nervous system. For example, SIBO, which is a condition involving inappropriate growth of bacteria in the small intestine, causes poor digestion of protein, fats, carbohydrates, B vitamins, and other micronutrients. So it’s no surprise that SIBO is strongly associated with depression and anxiety because our brains require proteins, fats, carbohydrates, B vitamins, and micronutrients to function optimally. On the other hand, stress has been shown to decrease normal transit time in the intestine and encourage the development of SIBO. Stressful stimuli are known to affect all kinds of different [gastrointestinal] functions, including motility and intestinal permeability. It’s not unusual to hear about people having to run to the bathroom before they give a speech. We know that both acute and chronic stress cause SIBO and inflammatory reactions in the gut, and chronic stress has been shown to exacerbate the disease activity in [IBS] and inflammatory bowel diseases like Crohn’s [disease] and ulcerative colitis. The stress also causes undesirable changes in both the quantity and quality of our gut microbiota. The most notable are reductions in Lactobacillus and bifidobacteria. In one study, researchers evaluated the impact of stress on the gut flora of students [who] were preparing for exams. They took baseline measurements of gut flora a week before the exam, and then they took measurements the day before the exam, on exam day, and five days after the exam. [They found] that the bacterial count of Lactobacillus and bifidobacteria declined significantly leading up to exam day, and that decline continued for about five days after the exam. On the other hand, gut dysfunction does affect the brain in several ways. Recent research has dramatically changed our perspective on the gut and its importance to overall health, and brain health in particular. The gut has a surface area of about 100 square meters if you [lay] out the intestine, which is 100 times that of the skin. If you stretched out the tissue in the gut on a flat surface, it would cover half of a tennis court. We now know the gut is a distinct nervous system in its own right, often referred to as the enteric nervous system or the “second brain” because of its size, complexity, and similarity in terms of neurotransmitters and signaling molecules to the brain. Over 75 percent of the output of our brain goes into the ponto-medullary complex, which, in turn, goes into the vagus nerve, which innervates the digestive tract. Three quarters of our brain output is going into our gut, if we put it another way. Then the gut sends signals back to our brain via the sympathetic and parasympathetic nervous system pathways. And the gut contains 400 times more serotonin and 500 times more melatonin than the brain. The gut flora has been referred to as a forgotten organ because it has a collective metabolic activity equal to any other organ of the body and it fully satisfies the definition of an organ, which is a collection of tissues joined in a structural unit to serve a common function. We also know that 70 [to] 80 percent of the body’s immune activity resides in the gut, specifically in the gut-associated lymphoid tissue. The gut contains over 100 trillion microorganisms from a thousand different species, with 10 times more microbes than human cells and a hundred times more genes than in our human genes. A hundred trillion is a nearly inconceivable number, but to put it in perspective, the number of stars in the Milky Way is estimated to be between 100 and 400 billion. That means you have between 250 and 1000 times more bacteria in your gut than there are stars in our galaxy. It’s not inaccurate to say that we’re more bacterial than we are human. According to Stanford microbiologist Justin Sonnenburg, “Humans can be regarded as elaborate vessels evolved to permit survival and propagation of microorganisms.” It’s kind of a creepy way to look at it, but technically, it’s true. Recent studies that have looked at the composition of our gut flora at birth have found that it directly affects the development of the hypothalamic–pituitary–adrenal (HPA) axis, which is the system that governs our response to stress. It consists of [the] hypothalamus and pituitary glands in the brain and the adrenals on top of the kidney. Signaling between our commensal gut flora and the central nervous system has been shown to directly impact this HPA axis, and this has been observed in everything from gut inflammation to pain to [IBS] to obesity. Other studies have shown that inflammation in the gut alters mood and causes depression, and our antioxidant defense system becomes overwhelmed when we suffer from depression, suggesting that oxidative stress [plays] a role there. Even skin biopsies from patients [with depression] show higher levels of oxidative stress. So how does inflammation lead to depression? Well, this is still being studied, but the current theory is that inflammatory cytokines that are produced in the gut escape the gut because it becomes permeable, travel through the bloodstream, cross the blood–brain barrier, and then activate the microglia, which are the immune defense cells in the brain. Microglia play an important role in repairing brain cells. But when they’re chronically activated by inflammation, they suppress activity in the frontal cortex, which impairs communication between brain cells and results in the characteristic signs and symptoms of depression.
What do dementia, IBS, depression, and acne have in common? They’re all linked to issues with gut health. Learn how your gut, brain, and skin impact one another and what you can do to support a healthy gut microbiome in this episode of Revolution Health Radio. #gutmicrobiome #functionalmedicine #chriskresser
Another line of evidence demonstrating the gut’s influence on the brain is the effect of probiotics and prebiotics on stress, anxiety, and mood. The first formal study of the psychological effects of probiotic supplementation involved 132 adults. Those with more depressive symptoms at baseline saw improvements in mood after taking a probiotic. A more recent French study found that probiotics correct stress-induced abnormalities in the gut flora by regulating the HPA axis in [the] early years and into adulthood.

The Gut–Skin Axis

Let’s move on to talking about the gut–skin axis. There are clear associations between gut disorders and skin conditions in scientific literature. For example, 14 percent of patients with ulcerative colitis and 24 percent of patients with Crohn’s disease have skin manifestations like eczema or psoriasis. Celiac disease is frequently associated with skin problems. For example, dermatitis herpetiformis affects a quarter of patients with celiac [disease], and [people with celiac disease] also have [an] increased frequency of mouth lesions, alopecia, and vitiligo. In a Chinese study examining the gut–skin connection, researchers found [that] 63 percent of those with skin conditions also had gastrointestinal symptoms. This is definitely consistent with my experience as a clinician. In fact, in my patient population, I would say the percentage is even higher. A recent report found that SIBO is 10 times more prevalent in people with acne rosacea, and correction of SIBO in those patients led to a marked clinical improvement. Researchers took patients with SIBO and separated them into two groups. The first group was treated with rifaximin until SIBO was gone, and the second group received the placebo. In the rifaximin group, 71 percent of patients with rosacea experienced complete clearing, 21 percent experienced significant improvement, 7 percent had no change, and 0 percent got worse. That’s a pretty significant difference; 92 percent either had a complete clearing or a significant improvement. Whereas in the placebo group, not a single patient experienced a complete clearing or significant improvement. That’s a pretty profound difference. Changes in gut flora also influence the skin. Altered gut flora promotes the release of something called substance P, which is produced in both the gut and the skin, and that [production] is attenuated by probiotics. In other words, if you take probiotics, not as much substance P gets produced. This is important because substance P is a neuropeptide that’s produced in the brain as well as the gut and the skin [and] plays a major role in skin health. It can increase histamine levels, which in turn triggers inflammation in the skin, and it may explain why, in a Russian study, 54 percent of patients [with acne] had significant alterations to their gut flora. A Chinese study involving patients with seborrheic dermatitis also found similar rates of disrupted gut flora. [Way back in the 1930s], Stokes and Pillsbury believed constipation was more prevalent in those with acne. There’s an older study using a bismuth test beverage, which reported intestinal stagnation in 47 percent of patients [with acne]. They also reported constipation as a clinical complaint in 40 percent of patients [with acne]. A more recent population study that looked at 13,000 adolescents found that constipation is more frequent in kids with acne. The question here, of course, is whether constipation is causing acne, or something else is causing both the constipation and the acne. While we don’t know for sure, a recent study provides some insight. In patients with chronic constipation, 65 percent had reduced levels of bifidobacteria, whereas 53 percent had no bifidobacteria at all. Bifidobacteria is very important for bowel regularity, so the fact that so many patients with chronic constipation had low bifidobacteria and other studies of patients with acne have shown low bifidobacteria, I suspect that disrupted gut microbiome is leading to both the constipation and the skin issues. This is why the common practice of prescribing antibiotics for acne is really not a good idea. Antibiotics may alleviate symptoms in the short term because they are effective against the [bacterium] that causes acne, which is Propionibacterium acnes. However, antibiotics also reduce levels of beneficial bacteria in the gut, particularly bifidobacteria, which, as we’ve just seen, contributes to acne and other skin conditions. This can create a vicious cycle where taking antibiotics for acne actually makes it more likely that you’ll have acne in the future and need to take antibiotics again, which perpetuates and deepens the cycle. Another line of evidence suggesting the connection between [the] gut and the skin is the observation that probiotics improve skin conditions. Stokes and Pillsbury made reference to the use of probiotics in fermented milk as [a] treatment for skin conditions in their work back in the 1930s, and other physicians of that time mentioned the popularity of using Lactobacillus tablets to treat acne. Once again, modern research has largely confirmed these earlier theories. Oral probiotics have been shown to decrease lipopolysaccharide, which is an endotoxin produced in the gut that can trigger acne and other skin problems, improve intestinal barrier integrity, and reduce inflammation. In an Italian study involving 40 patients with acne, Lactobacillusand bifidobacteria plus standard care worked better than standard care alone. And a recent study of 56 patients with acne showed consumption of a fermented dairy beverage improved acne over a 12-week period. The beneficial effect of probiotics on the skin might explain why pasteurized, unfermented dairy is associated with acne and fermented dairy is not. I haven’t seen studies on raw dairy and skin health, but I suspect that it would either not be associated or would have a lower association than pasteurized dairy. Probiotics in fermented dairy, and to a lesser extent raw dairy, can reduce systemic inflammation and oxidative stress, which are both elevated when acne is present. They also regulate the release of pro-inflammatory cytokines within the skin. Fermentation of dairy reduces levels of insulin-like growth factor 1 (IGF-1), which is a growth-promoting hormone similar in structure to insulin by more than fourfold. That could explain why fermented dairy doesn’t have the same effect as non-fermented dairy. Lastly, despite insistence from dermatologists to the contrary, diet certainly does influence skin conditions. I know you’ve probably experienced this yourself, and I think one of the main mechanisms is the gut flora. Most people know this intuitively. I’ve talked to many patients who’ve come to me for skin conditions, and they never accepted their doctor’s assurance that diet didn’t play a role. But we don’t need to rely on our own experience here. We know from anthropological research that rates of acne [were] extremely low in hunter–gatherer populations that followed a traditional diet. Those diets were rich in foods that were beneficial for gut flora like soluble fiber and starchy tubers, and they also didn’t take antibiotics, and had less contact with other factors in the modern world that can disrupt our gut flora and threaten our gut health. On the other hand, the typical Western diet is devoid of, or at least very low in, a lot of these beneficial fibers, high in processed and refined carbohydrates, and associated with acne and lower levels of Lactobacillus and Bifidobacterium.

The Brain–Skin Axis

Let’s move on to the brain–skin axis. The skin is a remarkably sensitive organ. It presents the largest interface with our environment, it’s exposed to a wider range of stressors than any organ, and that is pretty much happening 24/7 throughout our entire life. The skin is exquisitely well-innervated. We have lots and lots of nerve endings there. It sends a high volume of signals to the sensory cortex in the brain, and many neuropeptides in the skin share common embryonic origin, which means there are certain peptides like substance P that are produced not only in the skin, but also in the gut and the brain. There’s a long list of skin conditions that are associated with chronic stress. Pretty much all of them, but I’ll name a few here. Psoriasis, atopic dermatitis or eczema, alopecia, urticaria, herpes simplex virus, vitiligo, lichen planus, and acne. And mental health impairment scores among patients [with acne] are higher versus a number of other chronic non-psychiatric conditions like epilepsy and diabetes. As is the case with the gut–brain and the gut–skin axis, communication is bidirectional between the brain and the skin. Some researchers refer to the skin as the “diffuse brain” because we’ve known for some time that the skin is influenced by neuropeptides and hormones like [corticotropin-releasing hormone] (CRH), [adrenocorticotropic hormone] (ACTH), cortisol, catecholamines, prolactin, substance P, and nerve growth factor. We now know that the skin is not only the target for these substances, which means it’s acted on by those substances, but can also produce them itself. In fact, studies have shown that our skin contains a fully functioning local HPA axis right there within the skin. I mentioned the HPA axis earlier, but let’s take a closer look at how this works. During the stress response, the hypothalamus releases CRH. Once that’s released, CRH acts on the pituitary in the brain to produce ACTH. ACTH travels through the blood and acts on the adrenals to produce cortisol, epinephrine, and norepinephrine (adrenaline). Cortisol then feeds back to the hypothalamus, which decreases CRH secretion in this negative feedback cycle. That’s the classic HPA axis response to stress, and it’s been well established for decades. What’s amazing is that the same cascade of hormones produced by the HPA axis response to stress is mirrored locally in the skin. It’s almost like a microcosmic or holographic stress response that’s going on inside of our skin. Studies have shown that CRH is expressed locally in the skin, and stress triggers the release not only of CRH, but also ACTH and cortisol in the skin. The skin contains CRH receptors, which are involved in this stress-induced exacerbation of skin conditions. What about hair? Stress has long been implicated as a possible cause of hair loss and [is] an aggravating factor at least. The hair follicle is one of the most hormone-sensitive tissues in human biology. It’s especially sensitive to key stress hormones, which act as hair growth modulators. Like the skin, hair follicles are not only the target of these compounds, [but] they’re also a source. The hair follicles contain [a] fully functioning local or microcosmic HPA axis, just like the skin and the central nervous system. Not only can stress cause skin problems, [but] skin problems can increase stress. This is a surprising one for most people. Skin health is not just about self-image and concern about appearance. There are real physiological mechanisms at work here. Histamine is produced in mast cells, and that increases the production of CRH in the hypothalamus and that activates our central stress response. Pro-inflammatory cytokines that are produced in the skin can induce sickness behaviors and depressive symptoms and may aggravate stress perception, and that creates a self-reinforcing feedback loop between stress and skin problems. Another way stress causes inflammation is by disrupting epidermal behavior. You’ve heard of leaky gut, [and] maybe you’ve heard of leaky brain. Here we’re talking about leaky skin. The main function of the epidermis is to act as a physical, chemical, and antimicrobial defense system. Studies have shown that stress impairs the integrity and protective function of that barrier, which leads to a decrease in antimicrobial peptides that are produced in the skin and an increase in infection and inflammation in the skin. One researcher in a paper I read referred to this process as a “nervous breakdown of the skin,” which I think really brings it into clear focus.

Tips for How to Improve Your Gut–Brain–Skin Health

Let’s talk a little bit about what this means from a practical perspective. It should go without saying that to truly address one point on this gut–brain–skin axis, we have to address all three. For example, we know that low stomach acid can contribute to SIBO, which can contribute to leaky gut and inflammation, and that can trigger or worsen mental health or skin conditions. Psychological stress or physical stress can lead to low stomach acid, SIBO, leaky gut, and everything I just mentioned. Even inflammation in the skin or skin disease itself can increase stress hormone production, which in turn leads to low stomach acid and that whole cascade of things I just talked about. So, we really want to take a comprehensive approach when we’re dealing with an issue on any point on this axis. Not surprisingly, diet should always be the starting place. By your presence here, I’m assuming you’re at least peripherally aware of the benefits of a nutrient-dense, whole-foods diet for overall health and well-being. Of course, that’s just as true for the gut–brain–skin axis. Fat-soluble vitamins, B vitamins, biotin, traditional fats, [and] long-chain omega-3 fatty acids are all crucial for the proper function of each of these three systems. On the other hand, anti-nutrients and toxins in the Western diet, like seed oils, trans fats, refined carbohydrates, and sugar, are antithetical to the health of the gut–brain–skin axis. Once you’ve dialed in the nutrient-dense, whole-foods diet, step two is optimizing your nutrient status. The gut, brain, and skin need at least 40 micronutrients to thrive. These are vitamins, minerals, trace elements, and phytonutrients, and recent research suggests that most Americans are not getting enough of several of these micronutrients. While a whole-foods diet should always be the foundation, challenges in the modern world have made it hard to meet all of our nutrient needs from food alone. These include a shift in diet patterns toward highly processed and refined foods, changes in soil quality which have reduced nutrient bioavailability in food, an increase in toxins like heavy metals and glyphosate in the food supply, the growing prevalence of chronic disease, which increases the demand for nutrients and decreases their absorption, a shift to a global, industrialized food system rather than a local organic food system, and an increase in the number of people taking prescription and over-the-counter medications that interfere with nutrient absorption. This is why I created the Adapt Naturals supplement line. It’s designed to close the modern nutrient gap so you can feel and perform your best and have optimal skin, brain, and gut health. The Core Plus bundle is our flagship product. It’s a daily stack of five supplements with everything you need to thrive, from essential vitamins and minerals to phytonutrients to mushrooms [and] tocotrienols. I suggest this for people who want to be sure they’re getting the optimal level of all the most important nutrients on a daily basis. You just set it and forget it. You can learn more at AdaptNaturals.com/CorePlus. You can also order the products individually if you need more flexibility. I created a quiz to help you choose which products are the best fit for your specific needs. You can find that at AdaptNaturals.com/Quiz. Step three is addressing any underlying conditions that might be present in the gut. These could include SIBO, infections, disrupted gut microbiome, etc. I have written a lot about this over the years. If you go to ChrisKresser.com and you click on the drop-down menu where all the eBooks are listed, [you’ll] see I have a free eBook on gut health, and you can often make a lot of progress just by following the suggestions in that eBook. There are, of course, times where seeking out the help of a practitioner is going to be necessary if you have infections or other issues that can’t be addressed on your own. [Another] free resource that might be helpful here [is my] eBook on nutrition for healthy skin, where I cover the top 16 nutrients that are most helpful for the skin and how to make sure that you’re getting enough of them. Again, just go to ChrisKresser.com and you can choose the eBook from the drop-down [menu] there. If you’re not already subscribed to my newsletter, I frequently write about gut, skin, and brain health [and] produce lots of free content there [like] videos, emails, articles, etc. So make sure to get on the list, and [I] hope that everything we’ve talked about in this podcast has been helpful and that those free resources will get you on the right path, as well. Thanks for listening, everybody. Keep sending your questions to ChrisKresser.com/podcastquestion. This episode was a result of a question that was sent in. So even though I’m not doing the Q&A format that we used to do, I still look at the questions and use them as a way of choosing topics for the shows. Thanks again for listening, [and I’ll] talk to you next time.
This episode of Revolution Health Radio is sponsored by Paleovalley. Paleovalley has a very special offer for our listeners. Head over to Paleovalley.com/Chris and use the code KRESSER15 to get 15% off your order.