Most replayed moment: Fix Your Gut: Improve Your Mind | Dr Will Bulsiewicz

Summary

Podcast Summary: ZOE Science & Nutrition
Episode: Most Replayed Moment: Fix Your Gut: Improve Your Mind | Dr. Will Bulsiewicz
Host: Jonathan Wolf | Guest: Dr. Will Bulsiewicz
Date: April 28, 2026

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Episode Overview

This episode dives into the vital connection between gut health and mental health, exploring cutting-edge science linking digestive wellbeing to mood, neurological disease, and overall vitality. Host Jonathan Wolf and gastroenterologist Dr. Will Bulsiewicz break down how the gut and brain communicate, how issues in one can manifest in the other, and what practical steps listeners can take to heal their gut for improved mental and physical health.

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Key Discussion Points and Insights

1. The Gut-Brain Connection

• Ancient Wisdom Meets Modern Science: Everyday phrases like "gut instinct" hint at the deep link between our digestive system and our mental state. Modern research is validating this intuition with hard science.

  • (A: 00:01)

• Irritable Bowel Syndrome (IBS) and Mood Disorders:

  • About 50% of IBS sufferers are also diagnosable with major depression or generalized anxiety disorder.
  • “At a minimum, 50% are suffering in a way where...they're in a depressed mood relative to other people.” (Dr. Bulsiewicz, 01:30)

• Which Comes First: The Gut or the Brain?

  • Longitudinal studies reveal gut symptoms typically precede mood disorders, not the other way around.
  • Similar patterns are seen in Parkinson’s disease, where gut issues, particularly constipation, are an early sign before neurological symptoms manifest.
  • “They become constipated first and then subsequently develop Parkinson's disease.” (Dr. Bulsiewicz, 02:56)

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2. Mechanisms of Communication: How the Gut Talks to the Brain

• Multiple Communication Pathways:

  • Chemicals (bioactives produced by gut microbes)
  • Immune system (70% of which resides in the gut)
  • Hormones and neurotransmitters (many made in the gut: ~95% of serotonin, 50% of dopamine)
    • Note: While serotonin itself doesn’t cross into the brain, its precursor 5-HTP does, impacting brain chemistry.

• The Vagus Nerve:

  • “Perhaps the biggest and most important is a pair of nerves, probably my favorite nerves in the entire body...the vagus nerves.” (Dr. Bulsiewicz, 05:03)
  • The gut houses 500 million nerves—five times more than the spinal cord—making up the enteric nervous system, sometimes called the "second brain," or as Dr. Bulsiewicz suggests, the "first brain" due to its evolutionary primacy.
    • “From an evolutionary perspective...We developed our enteric nervous system before we developed our central nervous system.” (Dr. Bulsiewicz, 06:30)
  • These nerves are constantly collecting information about digestion, immunity, and even the gut microbiome, sending consolidated updates up to the brain.

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3. The Role of the Gut Microbiome

• Microbes as Mood Influencers:

  • Short-chain fatty acids (SCFAs) like butyrate, acetate, and propionate, produced when fiber is fermented by good gut microbes, have widespread anti-inflammatory effects and soothe gut nerve sensitivity.
    • “The most anti-inflammatory chemical that exists are the short chain fatty acids, butyrate, acetate and propionate.” (Dr. Bulsiewicz, 09:48)

• Overlap in Disease Mechanisms:

  • Major depression, Parkinson's, and even Alzheimer's show similar gut microbiome changes: loss of microbial diversity, reduced anti-inflammatory microbes (like bifidobacteria and lactobacilli), and an increase in inflammatory species.
    • “Similar changes in terms of loss of diversity and more inflammatory microbes and less of the protective ones.” (Dr. Bulsiewicz, 09:10)

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4. Actionable Advice: Improving Gut and Mind

• Diet Recommendations:

  • Short-Term: In severe gut sensitivity, a low-FODMAP or low-fiber diet can temporarily ease symptoms. (FODMAP = Fermentable Oligo-, Di-, Mono-saccharides And Polyols—specific carbs that feed gut microbes and produce gas.)

    • “The key with this, which is something you actually experienced...you were told, okay, go low fiber.” (Dr. Bulsiewicz, 12:05)
    • “The result is that you feel better in terms of your irritable bowel syndrome. The data are clear... will generally experience an improvement in their gut symptoms.” (Dr. Bulsiewicz, 12:24)

  • Long-Term: Restriction should be temporary—gently work to reintroduce FODMAPs, fiber, and a diverse range of plant foods for optimal gut health.

    • “Where we want to be is to include fiber, to include FODMAPs, to include a lot of variety of different plant-based foods in our diet because that's what makes our gut microbes thrive.” (Dr. Bulsiewicz, 13:10)

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Notable Quotes & Moments

• On the Prevalence of Mood Disorders in IBS:

  • “Up to 50%, at a minimum, 50% are suffering in a way where...if you were to measure their mood...they're in a depressed mood relative to other people.” (Dr. Bulsiewicz, 01:30)

• On Gut Issues Preceding Neurological Disease:

  • “They become constipated first and then subsequently develop Parkinson’s disease.” (Dr. Bulsiewicz, 02:56)
  • “100% of my patients that have Parkinson’s disease are constipated.” (Dr. Bulsiewicz, 02:57)

• On the “First Brain”:

  • “We developed our enteric nervous system before we developed our central nervous system...this actually came first.” (Dr. Bulsiewicz, 06:30)

• On Gut Microbiome Repair:

  • “Where we want to be is to include fiber, to include FODMAPs, to include a lot of variety of different plant-based foods in our diet because that’s what makes our gut microbes thrive.” (Dr. Bulsiewicz, 13:10)

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Timestamps for Key Segments

• 00:47–02:47 — Gut symptoms, mood disorders, Parkinson’s and the order of onset
• 03:59–06:18 — How the gut communicates with the brain: chemicals, nerves, immune system, neurotransmitters
• 06:19–08:18 — The enteric nervous system’s evolutionary and biological importance
• 08:18–10:47 — Microbiome, short-chain fatty acids, and parallels between gut and brain disease
• 11:06–13:26 — Fiber, FODMAPs, restrictive diets vs. reintroducing diversity for lasting gut health

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Conclusion

The episode underscores that our gut is at the root of not just digestive health, but also emotional and neurological wellbeing. For lasting improvement, nurture your gut microbiome with variety and fiber, but be gentle if your gut is hypersensitive—gradual change is key. The interplay between gut and brain is complex, but with practical dietary shifts, you can promote better health on both fronts.

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This summary captures the core science and actionable tips from Dr. Will Bulsiewicz and Jonathan Wolf, offering clear takeaways for anyone seeking to “fix their gut and improve their mind.”

Transcript

[A]

Hello, and welcome to Zoe Recap, where each week we find the best bits from one of our podcast episodes to help you improve your health. We've all heard phrases like gut instinct or trust your gut, and these sayings hint towards a sort of mind in your midriff. And it turns out there's actually some truth to it. Emerging science reveals that the brain and the gut are closely connected, constantly exchanging signals through an intricate network of nerves. So the question is, if they're so tightly intertwined, can treating one help heal the other? I'm joined by gastroenterologist Dr. Will Bolsewicz to unravel the mystery of this connection and find out how we can use it to our advantage.

[B]

There is tremendous overlap between digestive health and mood, and we see this represented in a powerful way in this particular condition, irritable bowel syndrome, because, yes, the criteria are not based upon your mood. The criteria are based upon your gut, based upon your gut symptoms. But the issue is that a huge percentage of these people simultaneously are dealing with mood issues. So it's roughly 50% of people that have irritable bowel syndrome that actually can be diagnosed with major depression or generalized anxiety disorder or both.

[C]

50% of people with IBS can be diagnosed with serious depression or anxiety or depression.

[B]

Up to 50%, at a minimum, 50% are suffering in a way where if you were to measure their mood, compare that to normal people, at a minimum, they're in a depressed mood relative to other people. But it is a very large percentage of people that are potentially able to be diagnosed with one of these two conditions or both, which are mood disorders. So there's this overlap between irritable bowel syndrome and these disorders of our mood. And the question that has come up is like sort of a chicken or egg thing, right? What causes what? And in the past, like, in the very beginning, Jonathan, when they first started studying this, they thought that actually it started in the brain and that these people had mood issues, they were depressed, and because they were depressed, they were feeling it in their gut. But then we actually lined up studies where we took a group of people that don't have any of these symptoms, and we track them. You know, you take 5,000 people, track them, and see what comes first. And it's actually quite fascinating, and it teaches us quite a bit where they discovered that actually, most of the time, it starts with gut symptoms. By the way, this is the exact same thing that happens in Parkinson's disease, where there's now research that Parkinson's disease starts with constipation and changes in the gut and then subsequently manifests with a neurologic health condition.

[C]

That's amazing. So I just want to make sure again that I've heard that right. You're saying Parkinson's, which is this terrible sort of neurological disease, actually starts with gut issues.

[B]

Yes. And gastroenterologists, Any gastroenterologist who listens to the show right now is going to raise their hand and be like, yes, I agree. 100% of my patients that have Parkinson's disease are constipated. They're all constipated. And so is it that they develop Parkinson's disease and then they become constipated? No, the answer is the opposite. They become constipated first and then subsequently develop Parkinson's disease. Two things with this. Number one, if you are listening to this and you suffer with constipation, I don't want you to hear that you're going to develop Parkinson's disease. The odds of that are very small. There are some people that this happens, but the vast majority of people who suffer with constipation, they don't move on to have Parkinson's disease. The point is, in this brain gut connection that exists, there can be the manifestation of disease in the gut and the manifestation of disease in the brain or in our mood. And they can be happening in a fashion that is actually they're connected to one another.

[C]

And how do we understand this connection today?

[B]

There's multiple ways that your gut is talking to your brain right now, as you and I sit here and speak to one another, your gut is talking to your brain. And some of the ways are with the production of chemicals which are what we call bioactive. So that means they can actually impact the physiology in your body. These chemicals, by the way, are often produced by your gut microbes. 70% of your immune system exists in your gut. And the immune system is able to activate things that can affect the entirety of your body and create inflammation. Also your hormones and your neurotransmitters that are produced in your gut. So it's interesting. When I finished medical school in 2006, I had learned about serotonin and things like this. And I didn't realize that there's over 30 neurotransmitters. I didn't realize there's that many. I thought they were X6. There's over 30 neurotransmitters. They are produced in the gut. 90 to 95% of serotonin is produced in the gut, and 50% of dopamine is produced in the gut. And so now these things can have influence in the gut, but also throughout the body, and particularly with serotonin. I just want to be totally clear because there's going to be someone who's a scientist who's going to want to make sure that I'm clear on this. The serotonin that's produced in your gut does not actually cross into the brain, but there's a precursor to serotonin called 5 hydroxytryptophan. And this 5 HTP actually has the ability to cross into the brain and signal and change how your brain works. And then the last but not least, perhaps the biggest and most important, is a pair of nerves which are probably my favorite nerves in the entire body, Jonathan, called the vagus nerves. All right, now, the vagus nerves start in our brain, pass through our skull, and descends down to our gut. And they're collecting information from your gut. There are in your gut 500 million nerves feeling and sensing by the microsecond. And all that information that gets collected by 500 million nerves. By the way, I should add that 500 million is a ridiculous number. So, I mean, I know that sounds like a lot. I mean, it sounds ridiculous, but like this, just to, like, compare this to your spinal cord, this is five times what you will find in your spinal cord.

[A]

Hang on.

[C]

So I've got five times more nerves in my gut, which, as far as I'm concerned, I can't have any control over, versus my spinal cord, which ends up controlling my legs and other things. I know I'm moving around all the time.

[B]

That's right. So, yeah, so you have five times more nerves in your gut. This is why we call it the enteric nervous system. Or some people will call it the second brain. I actually would challenge that. I would call it the first brain. Serious. Well, okay, so here's why. From an evolutionary perspective, for you and I to be here, it required us to evolve and mature our brain. But the problem is that a tree can't grow until it puts down roots. The roots must come before the tree grows up. The brain cannot be strong without nutrients. We developed our enteric nervous system before we developed our central nervous system, which is our brain. So from an evolutionary perspective, this actually came first. And these 500 million nerves that we have are constantly feeling and sensing everything that's happening. That includes the immune system. You have 1.3 trillion cells in your gut that are literally right next door to these nerves. Like, they're right there. And then Feeling and sensing the 38 trillion microbes that are like across a paper thin wall that may or may not have holes in it, which is what we call the gut barrier. And there's the 38 trillion cells, they're right there too. And so these nerves get to feel inflammatory cytokines, things that your immune cells create, that's inflammation and also come into contact with the chemicals that are being produced by your gut microbes. And they collect this information. Jonathan, consolidate it all into two nerves that run from your gut all the way up through your chest, past your heart, through your lungs, through your neck and to your brain. That's the vagus nerve, this is one of the 12 cranial nerves. And then that information your brain can action based upon this, you think that

[C]

there might be this central explanation around the gut microbiome. How does that play into all this complexity of the nerves and the two way gut brain axis you were talking about?

[B]

The chemicals that are produced by our gut microbes have an influence throughout our entire body and that includes on your brain. And if we think about these individual things, whether it be the serotonin levels which impact our gut rhythm, which affects whether or not we have diarrhea or constipation, or a Bristol 4 that's influenced by our gut microbes, when we think about the sensitivity of these nerves, actually there's research, Jonathan, that with fiber, fiber comes into contact with our gut microbes, produces short chain fatty acids like butyrate, acetate, propionate, and these short chain fatty acids actually have a soothing effect on the nerves that are lining our gut. So if you're asking me the question, like what's a natural way to reduce gut sensitivity? That's the answer. And simultaneously we have discussed how our mood is affected. Research is now showing, Jonathan, that the common tie between major depression and Parkinson's disease, and by the way also Alzheimer's disease, is inflammation inside the brain. So our immune system is getting activated in both of these places, both in the gut and in the brain. And if you want to reduce these things, the most anti inflammatory chemical that exists are the short chain fatty acids, butyrate, acetate and propionate. And so it's kind of interesting to take that into consideration when we think about people that have irritable bowel syndrome and if you zoom in on their gut, what you would see is the gut microbiome is damaged, there's a loss of diversity, they've lost the anti inflammatory microbes like bifidobacteria and lactobacilli they're not as well represented as they used to be. And there's an increase in the pathogenic microbes, the inflammatory ones. All right, so this is what we see in IRO bowel syndrome. Well, actually, it kind of is in parallel to the same changes that we would see in a person who has a major depression. Similar changes in terms of loss of diversity and more inflammatory microbes and less of the protective ones. So when we look at this whole picture, we start to see that the changes are occurring within the gut and the manifestation can affect gut rhythm, gut nerves sensitivity, and simultaneously can affect our mood.

[C]

So it feels like the perfect time to switch to. So what can you do about it? And I think, you know, Will, we always like to make sure we cover really actionable advice. So if we understand that the mechanisms that end up leading to ibs, you know, start back with this damage to the gut microbiome, what can you do about it?

[B]

Right. So the advice that you received was to cut fiber.

[C]

Correct.

[B]

I understand why they said that on some level, if the only thing we cared about was improving your symptoms, fiber is hard for the gut microbes to digest. So in theory, if you cut fiber, you may feel better. There's research with a dietary approach called the low fodmap diet, which is something that we've discussed before on the show. So FODMAP is an acronym. It's super nerdy. I'm going to put it out there. But you don't have to memorize this.

[C]

No test afterwards.

[B]

Yeah, so fodmap. Fodmap, Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols. Basically, what this is saying is these are carbohydrate based foods that are fermented by our gut, by our gut microbes. And in the process of fermenting them, they produce gas. And you know what gas can do? Gas can distend. Gas can activate those nerves that are very sensitive. So the low fodmap diet, the concept is if we reduce these specific fermentable things, then we may actually make it easier on our gut microbes, make it easier on those sensitive nerves, and the result is that you feel better in terms of your irritable bowel syndrome. The data are clear. People who follow this dietary pattern, if you have ibs, will generally experience an improvement in their gut symptoms. But there's a key with this, which is that, and this is something that you actually experienced, you were told, okay, go low fiber. And then Ultimately, when you followed the Zoe program, you found that actually an approach that's focused on abundance and variety is a superior choice. So when we take this sort of restrictive approach of reducing, it should be temporary. And ultimately we want to work towards from this, like start with this, reduce FODMAP intake and then we want to start to reintroduce these things, gently increasing them over time. Because ultimately where we want to be is to include fiber, to include fodmaps, to include a lot of variety of different plant based foods in our diet because that's what makes our gut microbes thrive. So it's just a matter of getting there. It's the process.

[A]

As you can imagine, hosting this podcast, running Zoe, juggling family life, it all keeps me pretty busy. So I try as best I can to stay energized and show up well in all those parts of my life by fueling my body with the right food, by exercising, and by adding a scoop of daily 30 to my meals every day. If you haven't heard of Daily 30 yet, it's the gut supplement designed by our gut health scientists here at Zoe. It's made of over 30 high quality hand picked plants including seaweed, fungi and different types of fiber. Better yet, it contains ingredients that support gut health digestion and energy, which is ideal for packed calendars and busy lives. Simply add one scoop a day to any meal for an extra boost of fiber and plant diversity. And because it tastes delicious on just about anything and adds a satisfying crunch, it quite quickly slots into your life, becoming a daily healthy habit you'll always have time for. By the way, whenever we talk about Daily 30 as a good source of fiber, we're required to say that it contains 4 grams of total fat per serving. Obviously that's all amazing healthy fats from plants, so order yours [e-mail] daily30. Thanks for listening and see you next time.