The Dr. Hyman Show
The Gut-Brain Connection: Why Your Mental Health Starts in the Microbiome
Mon, 24 Mar 2025
The connection between mental health and metabolic health is far deeper than once believed, with growing evidence showing a powerful, bidirectional relationship. Inflammation, poor diet, and gut dysfunction are now recognized as key drivers of both physical and psychological illness—often hiding in plain sight. By addressing root causes such as blood sugar imbalances, nutritional deficiencies, and microbiome disruption, many chronic mental health conditions can improve or even resolve. This emerging science challenges the traditional separation of mind and body, pointing instead to an integrated approach where healing the body becomes essential for healing the brain. Recognizing this link is crucial in shifting the future of mental health care. In this episode, I discuss, along with Dr. Chris Palmer and Dr. Shebani Sethi, why our diet is so closely related to the state of our mental health. Dr. Chris Palmer is a psychiatrist and researcher working at the interface of metabolism and mental health. He is the Director of the Department of Postgraduate and Continuing Education at McLean Hospital and an Assistant Professor of Psychiatry at Harvard Medical School. For over 25 years, he has held leadership roles in psychiatric education, conducted research, and worked with people who have treatment-resistant mental illnesses. He has been pioneering the use of the medical ketogenic diet in the treatment of psychiatric disorders - conducting research in this area, treating patients, writing, and speaking around the world on this topic. More broadly, he is interested in the roles of metabolism and metabolic interventions on brain health. Dr. Shebani Sethi is a double board-certified physician in Obesity Medicine and Psychiatry. She is the Founding Director of Stanford University’s Metabolic Psychiatry program and Silicon Valley Metabolic Psychiatry, a new center in the San Francisco Bay Area focused on optimizing brain health by integrating low carb nutrition, comprehensive psychiatric care, and treatment of obesity with associated metabolic disease. This episode is brought to you by BIOptimizers. Head to bioptimizers.com/hyman and use code HYMAN10 to save 10%. Full-length episodes can be found here: The Hidden Connection Between Gut Health & Mental Health That Therapy and Drugs Cannot Fix A Harvard Psychiatrist Rethinks Mental Health As A Metabolic Disease How Does Ultra-Processed Food Affect Our Mental Health?
Chapter 1: What is the gut-brain connection?
You're more likely to have a heart attack, for example, if you have depression, and you're more likely to develop depression after you have a heart attack.
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That's why I've been busy building several passion projects to help you. If you're looking for data about your biology, check out Function Health for real-time lab insights. And if you're in need of deepening your knowledge around your health journey, check out my membership community, the Hyman Hive.
And if you're looking for curated and trusted supplements and health products for your health journey, visit my website at drhyman.com for a summary of my favorite and thoroughly tested products. We have a mental health crisis. Globally, 300 million people are suffering from anxiety. 280 million people are suffering from depression.
Now, from treating thousands of patients over the last 30 years, I've learned that depression is mostly not in your head. It's in your body. When I treat patients' gut issues, and this is something I just discovered almost by accident, their mental health would magically get better. But it wasn't magic. It was science. I just didn't understand at the time. It's not magic.
Gut dysfunction is not the only cause of our mental health crisis. There's a lot of things that are driving it, but it's a major factor that's often unaddressed. Now, when your gut is unhealthy, when it's inflamed, your brain is unhealthy and also inflamed. When we fix... the gut, then brain health, mood, memory, focus, and mental health all improve. Now, why is this important?
Inflammation is a huge driver of most of our mental health issues from depression, anxiety, autism, ADD, even things like Alzheimer's, schizophrenia, bipolar disease, all linked to inflammation of the brain. And where is this inflammation coming from? Obviously our diet, but also from our microbiome. And I learned this early in my medical practice.
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Chapter 2: How do magnesium levels affect mental health?
Maybe you're so nervous you had to run to the bathroom, right? This is the gut-brain connection at work. There was a study that looked at more than 1.2 million hospitalizations for irritable bowel and 4,000 hospitals.
And people with IBS or irritable bowel syndrome had three times higher risk of anxiety, two times greater risk of depression, and then two times greater risk of suicide ideation, meaning they were thinking of suicide versus the general population. Now we used to think that anxiety caused IBS. But now we know it's the other way around and a little bidirectional. So think about that.
It's not really the stress or anxiety or mental health issues that's causing irritable bowel. It's the change in the microbiome and the irritation, inflammation to the gut lining and the enteric nervous system that feeds back to the brain. It creates an irritable brain. So irritable bowel leads to an irritable brain. So before we dive any deeper, let's define the features of this gut-brain axis.
The gut, which basically we talked about, is the GI tract. It starts at your mouth and it goes to your anus. It includes esophagus, stomach, small intestine, large intestine, all the way down to the bottom. The vagus nerve is the longest nerve that comes from your brain called the cranial nerve.
It travels through the brainstem to the gut and it connects the gut to the central nervous system and it goes through the entire higher GI tract. Think about it. You've got huge amounts of gut. If you, if you laid out your small intestine flat, it would be the surface area of a tennis court. And then there's your large intestine and then your esophagus. So all that is really important.
The vagus nerve connects to other things like your heart and lungs and so forth. But this vagus nerve is a really important part of your nervous system called the parasympathetic nervous system. This is the relaxation nervous system. It also is called the autonomic nervous system or automatic nervous system.
So it's not usually under our willful control, although we can regulate it through various practices. The yogis have been doing this for centuries. It regulates involuntary sensory and motor functions. You say, I'm going to move my arms. You move your arm, but you'll go, oh, I want to digest my food. Can you please digest the food in there? Can you please regulate my heart rate?
Can you control my blood pressure? You don't really think about it. These things happen automatically. A lot of this happens through this automatic system. There's a lot of signaling that happens through this nervous system. For example, it helps control appetite. And how does it do that? Through a peptide hormone called GLP-1, right? You might've heard about this. This is...
Ozempic, Rigobi, and so forth. Manjaro, these are drugs now, quote drugs, but they're not really drugs. They're just mimicking your body's own GLP-1 at a much higher concentration. This is also known as the satiety hormone. I mean, it makes you feel full, which is why people don't eat because they take this shot and they don't feel full.
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Chapter 3: Why is gut health crucial for mental health?
In autism, they're using these mitochondrial cocktails and supplements to help.
So, and that's where when I read your book, I was a little embarrassed. Because if you want the roadmap to, if you want the self-help version of how can I fix my mitochondria, I feel like your book, Ultramind Solution, is that roadmap. It involves improving your diet. Exercise plays a role. Stress reduction plays a role. Toxins can play a role. Hormonal dysregulation can play a role.
And these can be wildly different in different people. And I think that's, you know, it's a point that you made in your book. It's a point that you make commonly. And so it's not that there is a one size fits all solution for people. So one person could have an autoimmune thyroid disorder and have, you know, a horribly low thyroid hormone.
And that person will suffer from both metabolic and mental symptoms. And fixing that problem is replacing thyroid hormone or somehow addressing the autoimmune disorder and correcting that. Another person could have an autoimmune disorder related to intrinsic factor and they could have malabsorption of vitamin B12.
Regardless of what they're eating, that person too could have both metabolic and mental symptoms or disorders as a result of vitamin B12 deficiency. The treatment for that might be vitamin B12 injections because they can't absorb B12. Very different treatments.
But you're addressing the same root problem or the same root cause, which is, in my mind, metabolic dysfunction or mitochondrial dysfunction. But lots of different things can cause mitochondrial dysfunction. And so that's the way I'm thinking about it. In my mind, mitochondria are front and center.
But there are hundreds of different inputs that can influence how well mitochondria function and how they're doing. And then the consequences of mitochondrial dysfunction are widespread, and they can have numerous effects on the brain, resulting in very different symptoms.
Some people might have ADHD, other people might have depression, others might have seizures, and others might have schizophrenia. And that probably depends on a variety of factors. What are the different, you know, components or environmental factors that are contributing to your disorder?
Or genetics or other things we may not even understand. Yes. Right? Yeah, it's so true. And I just remember being in my clinic, you know, looking at the patients I saw and seeing not really treating their psychiatric problems, but they would come in with autoimmune disease or digestive problems or arthritis or whatever, migraine. And I would just do what I did.
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Chapter 4: What role does inflammation play in mental disorders?
And really make sure you're getting good nutrition, you're exercising maybe more than you normally even do, getting good rest, trying to decrease stress levels, those types of things, in order to allow your body to reset, in order to allow your body to recover from that assault on it.
One of the best doorways to the mitochondria is... Exercise, right? It stimulates the growth of new mitochondria, improves the function of mitochondria. It's quite important. And it also cuts down inflammation and activates your antioxidant enzymes. It has so many benefits. And we know it's better that they quill into many drugs for depression if you just exercise regularly, vigorously, right?
And we know that diet also plays a role. And one of the challenges, and I wonder how do you address this with your colleagues? Because this is something I've found even at Cleveland Clinic, working with some of the researchers, they're like, Well, we can't do everything at once. We can't do diet and exercise and supplements and sleep.
And I'm like, we can only do one thing at once because we don't know what's going to work. And I'm like, wait a minute. If you want to grow a nice garden, you don't just go, I'm going to give the water the plant water only, but no soil or sunlight. And then I'm going to give it sunlight, but no soil or water. It doesn't respect the laws of nature.
So how do you kind of battle that within the medical paradigm? Because it's really tough. We're looking for the single drug, for the single disease, or the single outcome, which is a model based on infection, which can work. But even then it's flawed because it depends on the biological terrain and why some people get sick and don't, or why some people die and don't. We see that with COVID.
Not everybody gets sick
sick or hospitalized or dies people who are chronically ill or overweight or age and do because their systems don't work as well so uh how do you address this i think it's a really i don't want to get you in trouble no no no it's a i i i kind of chuckled as you were saying your garden uh analogy because i've used that exact analogy with people as well i've uh um uh and uh
I think most athletes and coaches know this as well, that if you want to become an Olympic champion, it's not only about exercise. It's about exercise and diet and sleep and get rid of any toxins. That means no drinking, no drugging, no anything, because you are trying to get your body in prime condition.
And, and it requires a multifaceted approach and they, those things are all interconnected and they're all going to relate to whether you can grow your muscles, whether you can get faster, improve your, you know, cardiac health, all of those things. And so I completely agree with you. And I think it's, it's a huge challenge in our field. To me, the lowest hanging fruit is,
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Chapter 5: How does diet influence mental health?
They are, unfortunately.
They're looking in all the wrong places for the nutrients. They're eating more and more food. And I think a study from Kevin Hall and others showed that if you let people eat as much as they want and you give them ultra-processed food versus whole foods, they'll eat about 500 calories more a day of ultra-processed food because they'll keep eating and they're hungry and they keep driving.
And you talk a lot about it in your work, about the biology of what these do to your brain in terms of dopamine and the addiction reward pathways in the brain that make you... literally become addicted to these compounds and how that affects you.
Right. So the rates of obesity and binge eating and addictive like eating are rising alongside the increasing dominance of ultra processed foods in the modern food environment. And there are several mechanisms as to how this works, some which act directly on the brain and some that indirectly act through hormonal signaling. So our body is very complicated and the brain is connected to the body.
And we used to learn in medical school that you have this blood brain barrier that you get across it. But that's not like the Berlin Wall. But in reality, it's it does leak. Right. And there are things that do cross.
And it's more like a coffee filter. You know, it's a sip.
Yeah, so ultra-processed food and sugar decrease our dopamine receptors and make us eat more compulsively. Much like addictive drugs, the highly processed foods, they trigger dopamine reward pathways and they invoke addictive-like behaviors, which have been well documented and include intense cravings, includes feelings of withdrawal when cutting down on ultra-processed food.
continuing to eat these things despite knowing the adverse consequences to it, and repeated attempts to try to quit. I'm describing addiction here, basically, and the consumption of larger quantities over time than intended.
People go, it's like emotional eating. It's not really biological, true addiction. What you're saying is this is really a true biological addiction, just like heroin or cocaine or alcohol, that you get withdrawal, you get cravings, you get increased need for more and more of the substance to receive the same pleasure.
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