Your gut’s feelings
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Learn more at ibm.com slash WatsonX. IBM, let's create. If you spend a little time on health and wellness TikTok, you can find lots of people talking about gut health. So some are doctors, some are scientists, some are patients, and they'll say stuff like, you need good gut bacteria. Sometimes they emphasize how gut bacteria can help with gut conditions like irritable bowel syndrome. But

But some TikTokers are making a much bigger claim. Good and bad bacteria living inside your gut can affect your mental health. There are TikToks about how gut health affects mood disorders like anxiety and depression. People giving testimonials about how changing their gut health changed their life. I have never felt better. I have had zero anxiety attacks. My depression has been so much better and my stress has been lowered.

And while some of the suggestions for how to improve gut health just involve eating or drinking more fermented things, "Kimchi, kombucha, someone said sauerkraut." other people are recommending dietary supplements and regimens of expensive pills. "And I will post them here because I cannot pronounce them at all." It's all part of a growing gut health industry that's already worth billions of dollars.

So, I'm Bird Pinkerton, and this week on Unexplainable, I've been trying to figure out if there's anything to these claims. And it turns out there is some really interesting science here, but there are also lots and lots of mysteries left to solve. Big questions like, what is a gut feeling? And what, precisely, is the link between the gut and mood or mental health?

So we're going to take a tour of some of the research into those questions. But first, a quick definition of a term that's going to come up a lot. The gut microbiome. So that's all the microorganisms living in our gut. Dr. Katerina Johnson is a biologist and gut microbiome researcher at the University of Oxford.

And she helped me understand that mammals like mice, chimps, dolphins, but also humans like you and me, we have millions of microorganisms living in our stomachs and intestines. Bacteria, but also fungi, parasites.

And they help us break down food, they attack the bacteria that make us sick, and they also interact with other parts of our bodies. They interact with our immune system, our nervous system, our hormones. So in many ways, our gut microbiome is almost like the center of our physiology. So that is the gut microbiome.

And our tour into the research about the connection between it and mood begins in the early 2010s, when some researchers got curious about the microbiome and stress or anxiety. They had noticed that a lot of people with gut conditions like irritable bowel syndrome had stress or anxiety. And they wondered, was that just because gut problems are really unpleasant? Or was there something more at play here? Was the gut somehow influencing emotions?

So they designed an experiment to find out, this experiment that Katarina ended up reading about as part of her PhD research years later. It was an experiment that relied on the quirks of lab mice.

Some mouse strains tend to have different temperaments from other mouse strains. In this experiment, the researchers chose two strains specifically for their temperamental quirks. So in particular, they chose one mouse strain that tends to be quite timid and tends to show kind of anxiety-like behaviors.

And another mouse strain that tends to be much more bold and exploratory. And if you're wondering how researchers measure mouse personalities? Obviously, you can't get inside the mind of a mouse, but there is a range of different tests that have been developed over the years in kind of like psychology and biology to try to understand, you know, kind of how a

animal is feeling. They can put the mice in a box with two rooms, one dark, one full of light. And the bolder mice are the ones that explore more or explore more in the brighter room, while the anxious and timid mice stay safely in the darkness. That's just kind of like one example. So the experimenters had these mice with mousy, not-so-mousy personality traits

And basically, they wanted to know. If you take the gut bacteria from this kind of like bald mouse and all the gut bacteria from this shy mouse, and you swap kind of the contents of that gut. Could you also change how anxious or stressy a mouse was? Would changing the contents of the gut affect these personality traits at all?

So they use something called a fecal microbiota transplant, which we've been doing some version of for centuries, possibly as early as the fourth century in China. But at the most basic level, a fecal microbiota transplant involves taking poop from one gut and putting it into another. And if all goes well, the microorganisms from the donor gut will then spread in the recipient's gut.

So the researchers did a version of this process, and the end result was that they had bold mice with timid mouse gut microbes and timid mice with bold mouse gut microbes.

Once the swap was complete, they ran their little mouse personality tests again. And they found that if you change the gut microbiome, it affected the temperament of the animals. So the aggressive mouse becomes shyer because it was colonized by the gut bacteria of the shy mouse and vice versa.

Now, this wasn't like a remake of Freaky Friday, but where Jamie Lee Curtis and Lindsay Lohan trade guts instead of bodies. Because the personalities were not totally swapped.

It's not like the kind of bold mouse becomes, you know, totally shy, but its temperament changes more to be more docile. And meanwhile, the timid mice were suddenly wildly bold. The shy mouse shows less kind of anxiety-like behavior, but not to the total extent of exhibiting the behavior of the other individual, but it becomes more like it. It's

Still, even without like a complete personality reversal, these shifts in timidity and boldness were pretty impressive. Because this study from 2011 was one of the first to really clearly show that behaviors could be transferred along with a gut microbiome, at least in mice.

This is exciting because then the implication of that is that our gut microbiome does contribute in some way, we don't know how much, to behavior.

There have since been follow-up studies, also on mice, drawing more connections between the gut and mood disorders and stress and personality traits. But while we do research on mice because mice and humans have a lot of similarities, like we have the same kind of organs, they develop in similar ways, mice and humans are also very different. Like mice can't talk to therapists, for example, to help with their emotions.

So the next question is, does the human gut microbiome make similar contributions to mood or emotions or stress? Katarina says she has started to see more research being done across species to see if the same kinds of effects hold up. So, for example... They've taken the gut microbiota from humans that are depressed, and they've then colonized the guts of mice with these bacteria.

And they find that the mice show symptoms characteristic of depression in both their physiology and their behavior. One of the ways that researchers measure depression in mice is pretty controversial. They'll put them in a tank full of water and see how long they swim.

which is called the forced swim test. So it's how much the animal kind of struggles, how much motivation they have to struggle before they give up. The researchers found that mice that got gut microbes from humans with depression gave up faster than mice with gut microbes from humans without depression.

And then there were other interesting results. The animals that were colonized with the gut microbiota of people who were depressed also show a more pro-inflammatory kind of profile. That means their immune system was more eager, like was reacting to more things in their environment, seeing more stuff as threats.

And humans with depression can also have more active immune systems, just like these mice. So there were kind of changes also at the physiological level that seemed to match what you might expect. All of which suggests that gut microbiomes might play some role in depression, even in humans. But this study was also done in mice. So then, like, the next obvious thing is to wonder, okay, so what about fecal microbiota transplants in humans? Would those affect people's moods too?

Katerina has looked at the research into this, such as it is. She says that fecal microbiota transplants are

pretty rare in humans. They're generally safe, but they can have side effects. And they're usually only used to treat severe intestinal issues like Clostridium difficile or C. diff. So this is an infection of nasty gut bacteria and it can be really hard to get rid of, even fatal. Still, even though Clostridium difficile patients don't have fecal microbiota transplants specifically to alter their mood,

Researchers have started to look and see if there's an effect to their mood from the transplants. There started being some interesting observations in these patients that had had the fecal transplant for Clostridium difficile, and then they found it ameliorated other conditions that they had, for example, depression, chronic fatigue.

And there have been some small papers detailing case studies for other conditions. Like, there was one where a few patients with irritable bowel syndrome had fecal transplants. And they found that the fecal transplant improved their kind of psychiatric symptoms. Including depression.

Now, it is possible that if someone gets a transplant and it helps with their IBS or their C. diff, they're less tired or less depressed because they're not struggling with severe stomach problems anymore. Obviously, these are just small trials and there's not enough evidence. It's very early days and there's still many unknowns with fecal transplants. But still, research like this was intriguing to Katarina.

So she decided she wanted to do a study of her own, and one that would not be limited to people with intense gastrointestinal issues. Her plan was to take a bunch of human gut microbiomes and look at the personalities of the people that they belonged to,

to see if she could spot any connections between the two. So she gathered more than 600 participants. She collected information about their diet, their lifestyle, their life history, gave them a series of questionnaires to figure out how social and anxious they were, how big their social network was.

And then she gathered the most important data of all. So people are sent a stool collection kit in the post. And so they take their sample and then they post it as soon as they can afterwards. And I was working with a company to actually do the kind of like sequencing. Katarina had all that poop sent to a lab, which helped her identify which microbes were in each sample, how many, how many different kinds.

Which meant that Katerina finally had a sense of which types of microorganisms each person had in their gut and how diverse their guts were, and also a sense of how social these people were and how anxious and stressed.

Now, she just had to crunch all this data together and look for patterns. I found that sociable people have a high abundance of certain types of bacteria. So, you know, we know from kind of like animal studies that the gut microbiome can affect how likely they are to interact socially. So the fact that I find that these specific gut bacteria are also differentially abundant in humans means

in relation to their social behavior does suggest that the gut microbiome may contribute to variation in social behavior that we see in the general population as well. She also found a link between those traits and how diverse a person's gut was. So more diversity was linked to less anxiety, more sociability. But it is possible that, for example, social people end up seeing more people

swapping bacteria with them, and that is what leads to a more diverse microbiome. We almost each have like almost our own personal microbial cloud, and we were always transmitting microbes between us. Katarina's work is another piece in a growing research argument that the gut really does seem to be connected to mood and personality, not just in mice, but also in humans. But...

Knowing that the gut plays a role doesn't really answer why it plays a role or how. Like, how could microorganisms down in the intestines of all places connect to boldness in mice or socialness in humans? Why would our poop have any connection to depression? Yeah, that's like kind of the killer question. Like, how does our gut microbiome really affect our brain?

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Well, Bill, now you know why you feel so bad. You mistreated your stomach all day long. No wonder you have a... Unexplainable. From Vox. There's a growing body of evidence suggesting that the microbes in the mammalian gut are having some kind of an effect on mood and personality traits. Mice, but also humans. So the next question is, how?

And the answer might lie in something called the enteric nervous system. People often call me the father of the enteric nervous system. And I say I'm not the father of that. I swear paternity to Perry, Dana, and Timothy, my three children, and no further.

So I didn't discover the enteric nervous system. I popularized it. Dr. Michael Gershon, father of Perry, Dana, and Timothy, longtime gut researcher and popularizer of the enteric nervous system. And in case his popularizing efforts have not yet reached you...

The enteric nervous system is the idea that the mammal gut has a brain of its own, almost, like a whole separate division of the nervous system that's sometimes referred to as a second brain because it has an unusual number of nerve cells. In humans...

There are hundreds of millions of nerve cells in the gut. That's a lot less than the billions of neurons in your head brain, which means that your gut nerve cells are probably not teasing out the nuances of Russian philosophy, for example. But Michael has been trying to work out what exactly they are doing ever since his early research days. And because I'm old, that was a long time ago. It was not that long ago. It was back in the 1960s.

But at university, he had been taught that the brain had total control over the gut. Everyone thought if the brain didn't tell the gut what to do, the gut was lost. It was just thought to be a dumb organ. The gut listened and paid attention and did what was told. But Michael's research and research that came after increasingly began to show that that wasn't true. Instead, a different picture started to emerge.

And in this picture, Michael says, the gut is like a middle manager and the brain is more like a hands-off CEO. It doesn't like to get involved with the messy details of running anything so revolting as what goes on in the bowel. Instead, it delegates. Delegates to the middle manager, these millions of cells known as the enteric nervous system. So the enteric nervous system

But there is a direct line of communication between the middle manager gut and the CEO in the head.

It's called the vagus nerve, which connects the two. The gut sends tremendous amounts of information up to the brain. Michael says the gut doesn't send the brain information about every single thing that's happening to that hamburger. Just like, ideally, a middle manager isn't emailing the CEO every few seconds to be like, Hey, I'm using the printer, like, gonna go write an email.

Instead, it passes up the important stuff. And a lot of that having to do with satiety. Like, hey, CEO, we're full. Hunger. All these things. But also, research in mice suggests, somewhere in this communication between the middle manager gut and the brain, there are other messages. Having to do with influencing mood and anxiety.

So this is where all of our pieces come together. We have the gut microbiome with all its little microbes interacting with the enteric nervous system, our gut brain, in some way.

And the idea is that the gut microbiome helps create signals that are then passed up to the brainstem by the vagus nerve and then go to the emotion centers of the brain. But the next stage really is trying to understand how our gut microbiome interacts with the vagus nerve and how it really stimulates it in the gut. Katerina Johnson again.

Both she and Michael say that we don't yet know everything we would like to know about how the gut microbiome and the gut brain interact. We don't have all the facts about how, precisely, microorganisms in our gut stimulate the gut brain or generate the signals it passes along. People are looking very carefully at what it is the microbiome synthesizes. You can imagine all your gut microbes breaking down your food, battling bad bacteria in your gut,

And to do that, they're synthesizing enzymes and generating waste.

And some gut microbes also make chemicals that look identical to the neurotransmitters hanging out in our brains. Serotonin, but also dopamine, GABA, noradrenaline, histamine, acetylcholine. Only about 5% of the total body serotonin is in the brain and 95% is in the gut. Which means that there are lots of fascinating chemicals sloshing around in our intestines.

And we know that at least some of those chemicals can interact with our gut brain. But at the moment, we don't really know whether it's certain microbes or certain chemicals and how it really kind of affects how we feel at a molecular level. Researchers want to know more about which chemicals or molecules might generate signals to the brain.

And they also have a lot to learn about what kinds of signals are passed along. Because take serotonin, for example. In our brain, it's connected to our happiness. So you might think like, wow, there's a lot of serotonin in my gut. My gut is just like a reservoir of unadulterated joy.

But it's not quite that simple. A lot of the serotonin in the gut is playing a very different role than the serotonin in the brain. It's kind of controlling the contractions of our gut. So you might know the process of peristalsis. So it's how our food moves through our intestine as it goes from, you know, our small intestine to our large intestine to our colon and then passes out the other end.

which means that researchers can't assume that a chemical like serotonin that does one thing in the brain always does the exact same thing in the gut. So there is a lot to untangle here. And even when or if researchers do figure out all the mysteries of the microbiome's relationship to the gut brain, there's still a lot more to learn because Katerina says that the gut microbiome might be communicating with the brain in other ways.

Like not just via the gut brain and the vagus nerve.

Some researchers, for example, are interested in how the gut microbiome is affecting the immune system, which could be a whole separate path for affecting our emotions. We don't really know the relative importance of these kind of different mechanisms. There's studies upon which all these ideas of the different mechanisms are based. And I think really now is trying to understand, are some of these mechanisms much more important than others?

Which brings us, finally, back to the beginning of the episode.

I've been taking my probiotics paired with a few other products. So that market of products is sort of growing up around this gut-brain idea. Did you know that there are probiotic strains for mental wellness? A lot of that market focuses on something called probiotics. Probiotics. Should you take them? Should you not take them? What are they? So these are foods or sometimes dietary supplement pills that introduce lots of new organisms into your guts, sometimes by the millions.

No fecal transplant required. Here are a few signs you may need a probiotic. Number one, if you've been dealing with brain fog, a probiotic can definitely help. And there are lots and lots of TikToks, videos on other sites, podcasts, whatever, explaining what probiotics can do for you.

The probiotic I'm taking has specific strains in it that help with stress, anxiety, and depression. There's going to be strains that are going to help with raise your serotonin levels so you feel like in a better mood and help with your GABA neurotransmitter so you feel more relaxed. Take minimum 30 billion up to approximately 50 billion once per day.

But right now, it's still not all that clear exactly how effective this stuff is. Katarina is doing some research on probiotics and their effect on mood. And it looks like we might have some interesting findings, so watch this space. But she says that currently, overall, researchers just don't know enough to make super specific claims. Like, yes, there are good reasons to think that our gut has some kind of influence on our mood.

A lot of the excitement around the microbiome field is well-founded. Like, it's at the center of our physiology. It can affect our immune system. It can affect our nervous system. It can affect our hormones. And hopefully, in time, maybe researchers will be able to give people extremely specific gut microbes and see specific results.

But our gut microbiomes are so complex and there are so many variations between people and so many unknowns still, that at least for now... This link between our microbiome and mental health is still in quite early days, so I think we have to be very careful. Careful about making claims that are too big or too bold or too confident.

And even if we do come up with better answers down the line, I think it's important to remember that our gut microbiomes are still only one piece of a much larger mental health puzzle. They are not the sole cause of something like depression or anxiety. So I can't just cure my anxiety with yogurt, unfortunately. As hard as I might try.

Michael Gershon's book is called The Second Brain, and you can find more of Katerina Johnson's research on her University of Oxford page, or you can watch her TED Talk, The Secret Power of Poo, for more on fecal transplants.

This episode was reported and produced by Bird Pinkerton. That's me. It was edited by Catherine Wells, Meredith Hodnot, and Brian Resnick. Music from Noam Hassenfeld. Mixing and sound design from Christian Ayala. Fact-checking from Zoe Malek. Random military dolphin trivia that brightened my day from Neil Dinesha. And travel tips that gave me Wanderlust from Manding Nguyen.

And if you have thoughts about this episode or ideas for the show, please email us. We are at unexplainable at Vox.com. And we'd also love it if you left us a review or a rating. Unexplainable is part of the Vox Media Podcast Network. And we'll be back next week.

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