You’ve Been Pooping All Wrong (And It’s Affecting Your Brain) | Dr. Trischa Pasricha

What is the one biggest myth as it relates to bowel movements?

That people should have one bowel movement a day. Like truly, that is the biggest myth. Our colon certainly is primed to have a bowel movement at least once in the morning, but that doesn't mean that's the only way to live and that's the best way to live. Americans think that having a bowel movement every third day or up to 3 times a day could be normal. So you're not weird if you're going after every meal.

Well, hey everybody, we're going to get right back to the podcast, but I want to share something with you that is very personal. You know, for decades I've been a practicing neurologist. I've been asking a single question: what makes a good brain go bad? More importantly, obviously, what can we do about it? And that question has led me to write my new book, which is called Brain Defenders. It's now available for pre-order, and in this book I'm going to take a hard look at where we are today and offer up some challenges as to where we are today in terms of what we're being told. You know, despite all the attention on targeting proteins, misfolded proteins like beta amyloid for Alzheimer's, we still don't really have any meaningful treatments for diseases like Alzheimer's and Parkinson's disease per se, and we certainly can treat symptoms, but as it relates to treating the underlying issue, We're falling short. Many of these approaches manage the symptoms at best, but without really addressing what's driving the underlying process. And this science is evolving, but what's really exciting is the emerging research on what I've called the microglia. These are the brain's immune cells, and when they're balanced, they are protecting, they are repairing. Well, when they're dysregulated— and we can talk about why that happens, and we do talk about it in the book— They can drive inflammation and lead to brain degeneration, often long before symptoms appear. And here's the empowering part: these microglial cells are deeply influenced by your day-to-day lifestyle choices—your nutrition, your sleep, your environment. And in the new book, Brain Defenders, I share both the science and provide a practical roadmap that'll help you calm inflammation, support supportive microglia, and really. Ultimately take control of your brain's destiny. And if you preorder your copy today at braindefenders.com, you can receive some special bonuses like a sneak peek at chapter 1, the full glossary for the book, and curated offers from my favorite brain health products, many of which I've discussed here on the podcast. This is a new way of thinking about brain health, and I truly believe that this book Hopefully, it's going to change everything. I can't wait for you to read it, and I think you're going to be as excited as I am about the information you're about to receive. That said, let's get right back to our podcast. Well, hello everybody. Welcome back to The Empowered Neurologist. I'm Dr. David Perlmutter, the host of this program. Today's episode explores a topic that every single one of us experiences, hopefully daily, And yet no one wants to talk about it openly. It's personal but universal. And as it turns out, what I'm talking about is deeply connected to the brain. My guest is Dr. Tricia Pasricha. She's a gastroenterologist and author of a fascinating new book. Here's the title: You've Been Pooping All Wrong. Now, the title is going to make you smile, but the science behind it is actually very serious and incredibly important. Dr. Patricia, let me tell you about her. She trained at Johns Hopkins. She comes from a family steeped in gastroenterology and represents a new wave of physician scientists, as it were, that are working on the cutting edge of what we call neurogastroenterology. And that's the study of how the brain and the gut communicate. In her book, she dismantles some long-held myths about digestion, things like constipation and Really what we think we know about our bowels and our bowel movements. But more importantly, she illustrates something that is profound, and that is the gut is not operating in isolation. It is exquisitely responsive to things like stress, our emotional state, our beliefs, and even deception. It's really some fascinating information that she's uncovered. In fact, at one point in the book, she describes research that shows that Students undergoing a stressful oral examination nearly experienced double their intestinal permeability. That's how powerful this gut-brain connection, or brain-gut connection, however you want to call it, really is. It is bidirectional. This conversation is about more than digestion. It's about basically removing stigma, removing shame, and replacing myth and science, and understanding how the nervous system And the immune system shape what happens basically where the sun doesn't shine. I think you'll find this discussion both eye-opening and finally liberating. Let's get started with this podcast. Well, Dr. Pasricha, welcome to our program.

Thank you so much for having me. Glad to be here.

As I said in the introduction, uh, and as I think your book makes so clear, uh, it's time. It is absolutely time. We got to talk about this very important bodily function that we need to poop. Every day and why it matters and why it's so heavily stigmatized. But I think you're going to make that very clear to us that it's time that it's not stigmatized anymore. So that probably answers the first question, I guess, which is why did you write this book?

Yeah, I wrote this book after I completed my training in GI Probably 5, 10 years ago. And probably the most profound thing I was struck by when I started seeing patients on my own was how many people would do that thing where they like linger at the door at the end of the visit and they'd be like, you know what, I have just like one more question. I'd be like, oh, what is it? And it'd be like, is this normal about me? And they'd like say— they'd ask something about their food. They're like, how many times am I supposed to go a day? Or is it normal if I have this color? Like, and, and I was like, oh, this is so interesting. And, and I was like, was this just, you know— but I saw that pattern over and over and over again that so many people just didn't seem to have a good understanding of like what the absolute basics of pooping looked like. Like they'd come in for some other reason, but then we'd kind of reveal that there was this big—

This is so important. Wow. Yeah.

Yeah.

I think we've all had that experience. Yeah. People just don't want to talk about it. And

they don't.

Gosh, you made it clear in your book. It's so important. This function is so critically important. So then you decided to

Yeah, well, you know, it's important, one, because there's this statistic that about 1 in 3 people, this came from the UK, 1 in 3 people will avoid talking to their doctor about their bowel symptoms because they're so embarrassed. And, you know, it's more than just like a question of our propriety. That's really a big problem when we're talking about early onset colorectal cancer, where we're not catching these younger people in these cases early enough. It's a big issue when we're talking about, you know, the fact that we're not catching people chronic GI conditions. And like you mentioned earlier, it's actually, you know, a lot of what I talk about in this book and I talk to my patients about, it's not just limited to the gut. A lot of times we think about fiber and exercise and everything as being like just a gut health issue. It's really for your whole body. And I think the gut is this window and this gateway to your overall health. And if you put off those symptoms, you're so embarrassed to talk about those symptoms. I mean, even the title of the book, which is You've Been Pooping All Wrong. The word poop, like, nobody, no 2 people agree on what the right word is for this, right? Like, like, when I write that word, often people will be like, you know what, is that, should we be saying that? Should we not say bowel movement? Probably in medical training for you, in my medical training, bowel movement was what we called this, right? And like, when you say that to a patient—

Defecation.

Defecation, yes, a defecatory disorder. When you say that to someone—

Defecatory disorder, I've never heard that term before.

The textbook way of saying these things, like we just, we dance around the concept. But imagine telling a teenage kid who comes to your clinic, like, well, I'm concerned you may have a defecatory disorder, rather than saying like, you've been pooping all wrong. One is gonna make them really stressed and concerned. And the other one is gonna kind of clear the room and make it a safe space for them to share what's been going on. And so we need to figure out what the right word is. And we should be comfortable with whatever word we decide on. But yeah, I mean, I think I had a different background than a lot of people. Like, I'm the daughter of a gastroenterologist myself, so I grew up using every possible word there is to use for this, and we just talked about it all the time. So I was really surprised when I realized not everybody grew up like me. And like, there are a lot of people who go to the bathroom, they don't look, they just flush and they move about their day, and they don't really like think about it afterwards. Or what's more disturbing is they fall into that 40% of Americans whose Bowel habits disrupt their daily lives. That's a huge percentage for something that we just really don't talk about out loud.

You mentioned something sort of in passing a moment ago, and I hadn't really thought that I would talk to you about this, but you mentioned colorectal cancer in younger people.

Yeah.

And you know, I didn't really put this in the notes to talk to you about, but it is important. The JAMA study that came out in late 2025 that really made it very clear that this is a Very big problem and increasing very, very rapidly over the past decade. Why don't you unpack that for me, just for our viewers, just for a moment?

Yeah. I mean, this rise in cases, specifically young early onset cases, has been troubling all doctors, but really gastroenterologists. Colorectal cancer is leading the way right now as of 2026 in terms of early onset colorectal cancers and mortality for younger people when it comes to different kinds of cancers. And what's Yeah. The good news, in a way good news, is that for older people, the complications, the death rates, those are actually declining. The rates are getting a little bit better as you're older, but they're not so much when you're getting young, for that younger group. And one of the reasons I think that we have this problem is something is changing in our environment. And there are these risk factors that we can talk about that I think about very specifically for colorectal cancer that I just think were not on our radar as being risk factors for cancer like 20, 30 years ago. Risk factors today. But the second half of this is suppose the cancer's there, it's brewing, we're late to catch it in younger people. We're catching them a little bit too late. The earlier we catch these cases, of course, the better the prognosis is because we can intervene sooner. And part of the issue here is that people dismiss, especially when you're younger, you kind of dismiss your bowel habits. Maybe it's because you're embarrassed. That's a third of people. Will defer talking to their doctor. A third of people, this was a study that came from the Colorectal Cancer Alliance, a third of people will defer their whole colonoscopy because they're so embarrassed by the procedure. And if we can break that stigma and also just raise people's awareness about, look, a change in your bowel habits, that's diarrhea, new constipation, maybe it's how thin your stool have suddenly become, that's not no big deal. It might be, and the most likely scenario is that it You know, and what we hope will be is that it is no big deal, but it's not always the case, and it's worth running by your doctor. And even more importantly, it's worth knowing what your own normal looks like. If you're not somebody who's in the habit of looking and getting a sense of what are the things that influence your bowel habits and really knowing your own body, you're not gonna be so attuned to when there's a change.

I think this is a bit of a paradigm shift that maybe your, hopefully your book will help move along for primary care doctors dealing with younger people, people in their 20s, 30s, and 40s, uh, that if that information is not forthcoming, that there's been a change in bowel movements, that they should query that. They should ask moving forward, recognizing, you know, this incredible explosion of colorectal cancers, pancreatic cancers, other GI-related cancers in younger people. So, you know, we have our recommendations as to when we should start colonoscopy, either, uh, virtual colonoscopy or true colonoscopy.

Yeah.

And even, uh, looking at stool for genetic Yeah. Do you think it's time that we revise those recommendations as it relates to the age at which they should begin?

I mean, that is the big conversation right now. It actually was somewhat recently, within the last couple years, that we moved it from 50 as the starting age to now it is 45. So we've shifted it a little bit because of this rising number of cases in younger people. And I think that that gets a good chunk of people, but you're absolutely right that it misses people who are even younger than that. I would say the kind of disturbing bit of evidence for me is even for those people who are that 45 to 49 year range who are now eligible, have been eligible for colorectal cancer screening for several years, only about 20% of them are actually getting their colonoscopies. And so we may, you know, at some point we may even lower that age further, but I still actually think we're not meeting that gap even when we do. And for the younger people who are like, say they're less than 45 and they're worried about it, there actually are, you know, certain groups of people who should be getting screened anyway and sometimes don't know it, right? So people who have a family history, oftentimes we know, I see this in my clinic all the time. Someone will say, yeah, my dad had some kind of cancer. I don't remember what it was, or I don't know what age he was. Maybe, you know, they're not in touch with that person, or they certainly don't know like what their aunts had, what their uncles have. And 2 second-degree relatives, that's aunt, uncle, grandparents, That'll buy you a colon cancer screening at a younger age, but you have to know the age, you have to know the diagnosis. And again, I think this does come back to the fact that we just in general don't talk about our medical problems with our family members, much less our GI problems. But it's really important that you know that because there actually is a big chunk of people that we, a quarter of cases that were younger, could have been caught earlier if they had just gotten age-appropriate screening according to their own family risk.

So age-appropriate screening, would that include stool for blood at a young— in the 30s and 40s? Is that something that, you know, primary doctors should be doing?

Yeah, that— so that stool test, or the blood test, is more recent. That data just came out within the last year or so, and it's on the market. And I think everybody says whatever test that you're going to be able to get is the best test in that moment, meaning that for some people, We always, we like to say the gold standard is colonoscopy. And we say that because the colonoscopy, as you know, can truly prevent cancer because we're removing those polyps before they become a cancer. But these other tests, like the stool kits, like Cologuard, and the blood tests, they are very good at detecting cancer. We're obviously not removing polyps and things that we detect, but some people just can't get the colonoscopy so easily. And it's like, you know, it can be hard that you have to take half a day off. You might get sedated. Like, it's a big deal. I definitely think that if there's someone who, for whatever number of reasons, is not gonna get the colonoscopy, but should be screened, let's take an easier path. And often that stool kit is the easy path. The blood test is so easy. Let's do it. And then let's just make sure.

So is in younger populations, is there a, uh, insurance approval for Cologuard in people in their 30s and 40s, or do they have to have an indication like family history?

Exactly. It's, there are certain criteria you'd have to meet if you're under 45. So once you hit 45. You get you get the screening that you want, but under that, if you have a family history, it should be covered. If you have things like inflammatory bowel disease, like these people need to be screened earlier. There are different groups of people, especially if you have a known like genetic condition, for example, you'll get screened earlier. But but someone with average risk and no symptoms, it wouldn't be covered by insurance. But if you have symptoms, and that would be things like rectal bleeding, abdominal pain, a new change in your pattern of bowel habits, all of those things. Could be, would be, should be covered by insurance.

And so we are seeing, uh, more and more people opting for total body MRI. Uh, I don't know, you know, how effective that is as a screen for colorectal cancer, but I bet it picks some of them up. And the other thing is people are getting, you know, very obviously now getting their genome sequenced and are finding things out, whether they've known about, you know, their uncles and aunts or parents, whatever. Now they're seeing if they have genetic markers or risk factors rather, uh, for, uh, risk here for, for colorectal cancer. And I wonder, um, you know, if when they interpret those results either from the company that did them or more appropriately with the ordering healthcare provider.

Yeah.

You know, if they can get into that and then nudge that individual to getting screened.

Yeah. I mean, I think you're, you're right. I, I don't know that there's been, well, I don't know that there's been good data about how well an MRI can pick up the polyps. Like the virtual colonoscopy is a special type of radiology protocol that's pretty good. But I will say that sometimes, you know, to your point, sometimes having that extra, knowing about that extra risk factor, getting that nudge is what motivates people to change. I mean, that's just human behavior and human biology. If somebody's coming in, no family history, average risk, but then I find a polyp, for example, and I say, look, You know, we have this early sign, it's not cancer yet, but it's on that path that, you know, there's like a 10% conversion rate to cancer for these polyps. There's few things more powerful for a lot of people to say like, wow, I, I should change my behavior. I should change some of the risk factors that I do have control over. We don't have control over everything. We can't make that risk zero. But, you know, it is empowering to know that we can make those changes. And sometimes just knowing that is the trigger that I think we all can, you know, benefit from. Yeah.

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Yeah, I completely agree with you. I mean, sometimes people ask me like, what would you do if you were in my shoes? What would you tell your mother to do, your sister to do? It's always colonoscopy unless there is some risk factor, like maybe there's some reason you can't tolerate anesthesia and that's like a specific situation. Yeah. But you're right that, you know, the stool kits, the way you like put your stool in a box, you mail it to a company, they send it back, those are actually, you know, they're great for detecting cancer. They're less good at detecting polyps. And I think the point that I, A lot of people don't understand is that the bigger public health point of colonoscopies is not to detect the cancer. We do that and we're glad when we do that, but it's really to prevent the cancers by getting those polyps and you can't do, and removing them, and you can't do that with any other test.

Yeah. And I would say full reliance upon Cologuard is also, I think, somewhat inappropriate. I think what we see with Cologuard is, you know, a fair number of false positives that are very worrisome to people when, you know, that test comes back positive and they indicate, yes, you need to follow this up with a with a colonoscopy. And, you know, during that period of time where they're told that and the colonoscopy, these people are really concerned. So there are a fair number of false positives. Not saying that people shouldn't get it. I mean, it's, it's a, it's an at-home, do-it-yourself kind of thing, and you get information that, you know, in general, I think is worthwhile. Um, you grew up the, the daughter of a gastroenterologist. How did that influence you?

Well, it's, it's certainly the reason I became a gastroenterologist. You know, my dad was a, and still is, He's a neurogastroenterologist, so he does what I do, which is we study the gut-brain connection. And that's a term that, you know, kind of came on the market like in the 1990s. It's a relatively new subspecialty as far as subspecialties go. But it was, I mean, I think the 1990s was really the birth of that field in some ways. And it was an incredibly exciting time for him because he was a researcher and he talked about his research every day with me and my siblings. And I've just never seen, I still haven't met anyone as passionate about their work as he is. And so, he really And he infected us with that excitement about GI. And of course, there was no stigma around talking about poop or talking about our guts. And I had— I came to find out later that not everyone talked about poop at the dinner table, but he would check in with us and just be like, hey, did you poop this morning? A lot of dads would ask, how was your day at school? Did you do your homework? He would just check in to make sure we had had a good bowel movement that day. And then if we didn't, he'd be like, hmm, what's going on there? And obviously no child wants to talk about poop.

My father, when I was a little kid, would tell us about a new neurological syndrome at dinner every night. And I remember him saying, you know, you shouldn't drink wine when you get older because you'll get Marcia Fava-Bignami syndrome. What in the heck is that? Well, actually, it's— that's how— so I share your experience. We'll leave it at that.

Started early for you.

Yeah. So I have to admit, many years ago, after I wrote a book called Grain Brain, I wrote a book called Brain Maker. And it focused on the influence of the microbiome mostly, but things going on in the in the gut as it related to the brain. And I have to tell you, it was a very popular book. But amongst my colleagues, there was a lot of pushback that I was talking about. You know how medications, especially antibiotics, quality of our water, stress, lack of sleep, etc., affected the microbiome and how that could. translate into an issue related to the brain. And that connection was, it was just very, very, I think, challenging for many mainstream neurologists and, and other types of physicians to make. So here your dad becomes a neurogastroenterologist early on. Uh, and how was that early on? Was he— what did people— was this in a research kind of environment?

Yeah, yeah. I bet he, I bet he had some similar experiences to you. And I think we We feel some of that today. I mean, if you think about it, I mean, 50 years ago, nobody was talking about the microbiome at all. And now today, it's hard to imagine almost any disease without putting a little bit of that lens of how the microbiome plays a role. But in neuro-GI, the way this field, the way we've thought about the gut-brain connection for really more than 100 years, like dating back to 1890s, we thought about that connection as being how the brain in our head influences the brain in our gut. I don't wanna offend the neurologist here, but like, we talk about this as the brain in our gut, not the second brain, as some people say, but it's on equal footing, I would say.

But at any rate— You mean the brain-gut connection, not the gut-brain connection?

Yeah, well, I go back and, yeah, yeah, yeah. But we thought, and we know this to be true through several decades of physiological studies, that when we're stressed, when we're feeling anxiety, when we're even depression, those things can have these changes in our motility, especially acute stress. Those studies were done throughout the 1950s, 1960s, Where, you know, we had this experience that we've all pretty— are probably familiar with in real life, like where maybe you're caught telling a lie and you get this sinking feeling in the pit of your stomach. Or like, I was a theater kid, and like if I blew my lines on stage, like I would suddenly feel so queasy. Like I could even think about that time right now and I'll feel that same feeling. Well, what is that feeling? You know, I mean—

You're doing great, by the way. Keep going.

Appreciate it.

You haven't messed up your lines yet.

Oh, you know, I gotta get back to Broadway one day. But somehow people had figured out that just thinking, having these thoughts that felt stressful, evoked fear, evoked anxiety, could cause both the stomach to slow down, and this is something that I studied, the stomach to slow down and not contract at the regular rhythm that it should, but simultaneously, it caused the colon to speed up and rev up. And that's also why a lot of people, like, right before their turn at karaoke, like, have to go to the bathroom. It's like a classic problem. But it wasn't until this field really grew and coalesced into neurogastroenterology that people started to look at the other side of that connection. And I think that's also around the time that the microbiome really entered the chat too, is like, how is the gut, how are the trillions of bacteria living in the gut influencing the brain? And what I remember learning from him, and I saw this too when I entered my own residency training, and that was like 2016, people were still thinking about a lot of chronic GI conditions, like IBS, for example. I think this is still true today for a lot of people, as being largely all in someone's head. Like, you know, the problem in IBS, the problem in a lot of these GI conditions, like functional dyspepsia, which is a vague term for chronic unexplained abdominal pain, is stress, is anxiety. And they were using that lens that we had used for, you know, several decades, more than 100 years, And it, they weren't applying a lot of the knowledge that we now have over several years of research that in disorders like IBS, the problem often starts in the gut and the problem starts in the gut and actually can lead. And they've shown this in experimental models. It can lead to the anxiety, can lead to the depression and things in the brain, in the brain, in our heads. But the tests that we do, like colonoscopies, we were just talking about, Those are very superficial tests. Like we're taking a look at the surface, we're looking at the mucosa, which is the lining of the colon. And when we get biopsies, we're just getting like a little bit of that lining off and we're looking, is there inflammation right then and there? What we're not doing is getting to the deeper layers of the muscle where the enteric nerve system lives. That's the brain of the gut. It has a network of millions of neurons that are living, but it's buried in the muscle layer. Standard biopsies, standard clinical tests are not gonna get any of those abnormalities, or we're not doing the right kinds of stains that we do in research settings. So it's very simple for a lot of people to say, like, well, look at all these people with long-term GI symptoms, all their tests are normal, it's probably all due to their stress, it's probably all due to their depression. And so for a long time, he was going against the grain, so to speak, and him and not just him— Write a book about that. Yeah, yeah. And saying, like, you know, there are all of these abnormalities If only we did the right tests for them. And the field has changed, like, you know, where neurogi started in the '90s and when I joined it, there's thousands of us now, which is really wonderful. It was really like the few, the proud back then. But even then, I encounter residents, I encounter medical students who will say, oh, the hallmark of IBS, and IBS is the quintessential example, so I keep coming back to it, but the hallmark of IBS is there's nothing wrong with them. There's actually nothing wrong, you know? Yeah. And that's absolutely not the case. We know that the nerves in the enteric nervous system will be triggered at a lower threshold, that there'll be a higher concentration of TRPV1 receptors in the colon, which is a receptor that signals pain to the brain. And there's all of these, and of course, there's microbiome changes. There's just like a myriad of changes, and yet, Somehow the story that gets told still can be one of everything is normal, this is a brain problem and not really a gut problem.

It's all in your head.

Yeah, and it's a hard thing to hear, especially because a lot of our conditions are predominantly affecting women, and there's this whole, of course, cultural piece to saying that and, you know, even veering off into hysteria, which goes part and parcel with a lot of these disorders for a long time.

You mentioned a study where students had to have an— I think it was an oral examination or an exam that wasn't an examination of their mouth. It was an oral exam. They had to respond and how they were noted immediately to demonstrate increased bowel permeability. And the reason I want to bring it up is because the whole notion of bowel permeability, what is the colloquial term, is leaky bowel. I think it's still not fully appreciated by mainstream gastroenterology. And yet I think you're, you know, very facile with that term and appreciate what it means. So let's first about— let's first talk about what does this mean, gut permeability? How is it measured and why it matters? And then I guess we should leave alone why the mainstream doesn't really pay attention to it.

Well, I can answer all of the above. Like, I think that the reason, you know, you'll meet 2 kinds of gastroenterologists, one which the neurogastroenterologist will be like, of course, increased intestinal permeability is real and we've been studying this and there's these studies that I'll tell you about. But you'll also meet a lot of gastroenterologists who are so wary of the misinformation around the term leaky gut on social media that they're like, leaky gut's not real, this is not a real thing. And then I think unfortunately they may not be familiar with the data around increased intestinal permeability and those links. And so they'll sort of just like, you know, shut the door to all of the information. And I will say it's true, I've seen a lot of, of misinformation about what leaky gut is, you know, how it manifests, um, online.

Yeah, I agree with that.

So I can see, I can see why, you know, someone might be like, oh, that's not real. But the truth is that increased intestinal permeability is very real. It has— plays an important role in our symptoms, a lot of the same symptoms that we ascribe to leaky gut, although not all. And, you know, the study that you're talking about is a great example of how psychological stress can induce these changes almost instantaneously in our guts. And so there was a group of students who had to like defend their college thesis in front of this panel of judges, and they measured their intestinal permeability in the moments leading up to having to give that oral exam and then afterwards. And they found, of course, that their levels of stress went up, their anxiety went up, their cortisol went up, and then so too did their intestinal permeability. After the exam was over, suddenly that intestinal permeability, those, those cells and those junctions closed again, and they felt a lot better and a lot of relief. Um, the problem is that I think we sometimes have people who come in and they say, I feel really bloated, I feel really ill, or like lots of different foods give me all kinds of problems. Um, and they'll, they'll see online like, you know, I think I'm checking all the boxes for leaky gut, and it's possible that intestinal permeability is playing a role in those symptoms. It certainly could be playing a role in pain. We've seen that in studies. And for me, the bigger question is, let's not stop there at saying intestinal permeability is our diagnosis per se. Let's ask ourselves if that's what's going on. And I'll be honest, and I'm sure you know this, we don't have a good way of testing for intestinal permeability in a standard clinic. We have a lot, like 4 different ways we can do this in the laboratory, and that's been used in studies. But for me, the more important question is, Let's assume you're having these increased rates of intestinal permeability. Let's ask ourselves why. Like, what are the main things that we know that have been well-studied that can cause it? And let's take them out. Let's just eliminate them from the picture and see if you feel better. And for me, those things are stress, which of course is easier to talk about eliminating than actually eliminating, but certainly psychological stress and physical stress can do that. Ultra-processed foods have been studied to increase intestinal permeability. Alcohol. Poor sleep, all of the things that are actually like quite boring, you've heard from your doctor a million times, all of those things do modulate your permeability. And one thing I sometimes tell patients, because I'm a, you know, where I practice, I'm a tertiary center, so I'm often like the 3rd or 4th opinion for people who have been dealing with long-term symptoms that they can't explain, whether that's pain or bloating or difficulty with their bowels. Sometimes I say, let's just do a full, And what I am trying to do is get at strengthening and fortifying their gut lining, where I say, for 2 months, we're not going to drink any alcohol. We're going to, to the extent possible, we're going to eat whole foods. To the extent possible, we're going to avoid NSAIDs. And however much possible, I want you to exercise and reduce your stress. And sometimes, 2 months of doing all those things at once, we rarely do try to optimize all those things at once. People say— Yeah, my gut symptoms got 30, 40% better. I'm not gonna tell you like I always get people 100% better, but anecdotally, a lot of people get a lot better when they do that. And then for me, I say, okay, there was something in what you were doing before we did this experiment that was probably triggering at least a good portion of these symptoms, causing that intestinal permeability, which we know can lead to local and sometimes systemic inflammation. Let's see how we can make this sustainable and, and make this a long-term pattern.

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Let's get your genes working for you, and let's get back to the podcast. You just said something I think that was really important, and I don't want it to be missed, and that is that how this gut permeability relates to systemic inflammation. Yeah. And, you know, when we recognize that across the spectrum of chronic degenerative conditions that the World Health Organization now characterizes as the number one cause of death in adults on the planet, Yes. That, you know, inflammation is playing a central role. So I think it's fair to say then that these are important dots to be connected between gut permeability and the mechanism that underlies the most common cause of death on the planet. So I think this raises our understanding of the importance of identifying gut permeability and then dealing with it. You know, we've been looking at research for an awful long time that has has evaluated the levels of antibodies created against lipopolysaccharide, or LPS, which shouldn't really be present. We don't— lipopolysaccharide is, for the viewers, it's the covering over gram-negative organisms in the gut. And when it leaches its way through a permeable gut lining, which it shouldn't, then it can be measured, and antibodies that our bodies produce against that can be measured as well. So When we see elevated levels of these antibodies and of LPS itself, it's an indication of permeability. These elevated levels are seen to correlate with Parkinson's and Alzheimer's disease and certainly with multiple sclerosis. So, you know, this notion of hyperpermeable or increased gut permeability, call it leaky bowel if you must, but it's really fundamentally so important. So you're right in— You know, the epicenter right now of a much broader story of being related to chronic degenerative conditions through this permeability issue. And when you contextualize it like this, it really kind of makes you want to have these conversations with, you know, kind of more mainstream, toeing the line gastroenterologists who don't really appreciate how fundamentally important this is because. And I think I'm— this is your interview, I'm speaking too much, but the point I want to make is that, okay, then ask yourself, well, what are all the issues that relate then to this increased permeability? And diet is certainly on the top of the list. You mentioned sleep, you mentioned stress, you mentioned other environmental issues that are important. But, you know, like Anne said, taking nonsteroidal anti-inflammatory drugs and H2-blocking drugs as well, acid-blocking drugs, changing the pH of the gut is not necessarily a good thing. as it relates to the diversity and functionality of our microbes. So that said, you know, when we look at data recognizing a dramatic increased risk of dementia and stroke in individuals who chronically take either NSAIDs or these H2-blocking drugs, we have to pay attention to what's going on in the gut. That gets us to a preventive mode. But how incredible that, you know, smart people like you are now making this information So available to everybody. So let's get back to the remove and replete and replenish, you know, the, the, the, what's been called the 4R program as it relates to the gut. And, and if you can maybe reveal how one could assess gut permeability in a clinical setting.

Yeah, there's a couple of different ways that we, well, I'm sorry. Let me rephrase. In a standard clinical setting, we don't actually have a great way of assessing intestinal permeability. There's actually not a standardized test. In a research setting, there are a couple of tests that we do, and some involve us directly getting a biopsy and doing different stains and trying to look at those tight junctions. There are some markers, and by tight junctions, for anyone listening, what I mean is, you know, that gut is lined with cells throughout that usually are very closely opposed to each other. And even they have, you know, like little gates that have cells and molecules that hold them together. There are some tests, again, that are more in a research setting that can measure pieces of those gates floating in the blood, like zonulin, for example, is one. And then there's also what they did in this study, looking at the students who were having this oral exam, they had them drink this non-absorbable sugar that in theory, you know, should not be something that gets excreted. And then you can measure the kind of the before and after in the urine. None of these have made it and been fully validated in a clinical setting because we don't know quite yet how that correlates to a particular phenotype or a particular disease state. I think this is sort of a, not a because it means intestinal permeability isn't real and isn't valid. It's more like a, we've just gotten ahead of where the research has taken us yet. And I hope and imagine actually it might be part of a clinical test that we're going to do in the next 10, 20 years once we hone it down, because each of these tests is actually— they each have flaws and none of them are perfect. But all of which is to say that for me in my clinic, when someone comes in worried about leaky gut, that's not the test. Like, I worry less about the test. I kind of just say, if you have these risk factors, we can assume you have it. Like, you know, like leaky gut is actually There you go. If we, through the lens of intestinal permeability, you and I right now, we, during our 24-hour day, we're gonna have increased intestinal permeability based on all these different things. After every meal. Yeah, exactly, exactly. And if we just say, let's assume that you have it, let's, I mean, because we know that, and let's say we want to figure out how much of that could be contributing to your symptoms, let's just take the steps that would reduce it. The reason I feel comfortable saying that is because the steps that would, in theory, reduce your intestinal permeability are also things that are just good for you in general. Like, it's not like I'm telling someone to do something that I feel like is like outside the science or a waste of their time or money. Yeah. And so, I find that people have good success with that. And you're right too that, you know, while there is this physiological fluctuation in our permeability throughout different things that happen during our day, meals, Certainly stress and like marathon runners are like really well described to have high amounts of intestinal permeability, not always a good thing. A lot of different diseases can be linked back to what may or may not be entering us through our guts and through the integrity of our mucosal barrier. And in fact, this is something I study in Parkinson's disease, but of course, probably in terms of, you mentioned LPS, I think the most well-understood, in my opinion, understood model of how intestinal permeability can cause, uh, in disease is liver disease. Like, your liver— everything that comes through your body through your gut is going to first pass through your liver. You know, it doesn't immediately enter your systemic circulation. It actually, you know, goes through your portal veins and it hits your liver. Your liver, over time, if it is continually exposed to toxins, it does a great job You know, most of the time it does really well, but over time, if it keeps— you keep having these hits, like you drink a lot of alcohol, that's the classic one, it will develop so much inflammation that it just cannot handle the load anymore. And then you start to see this breakdown where more of those toxins then get past the liver and they enter the systemic bloodstream, and then the scar tissue starts to form and your liver less and less can do its job appropriately. So we know in several other disease states That you can link back the problem ultimately to intestinal permeability, and then further, the triggers of that intestinal permeability, which often can be alcohol, it can be ultra-processed foods, it can be all these things in our environment.

Yeah, I, you know, you get to be hard-pressed these days to find an upside of alcohol. I mean, people talk about, well, it makes you more social. I mean, how much more? Where's the benefit of that? I don't know. Um, getting back to the bowel permeability issue though, I think, you know, clearly things that lead to dysbiosis or changes in the diversity and functionality of our gut bacteria play a— plays a role in increasing permeability. You know, loss of species like Lactobacillus plantarum, for example. That said, where I'm going with this is, tell us what you feel the role would be for— let's start with probiotics, but I want to make sure we cover prebiotics as well.

Yeah.

How effective would

Yeah, that's a, that's a really good question. In fact, that's like a very common thing that people come to me with. Like, they'll, they'll want to try supplements and probiotics, and, you know, the data is not as good as I think we want it to be in, in GI. Like, we wish, and I hope the field gets there in the next couple of decades, like, hopefully sooner, but, um, I wish I could say that personalized microbiota-directed therapy is ready for primetime. And that means like, you know, it can be a range of things, but it can be taking a probiotic, especially when it's one that seemingly is targeted towards whatever abnormalities someone might've detected on your own individual microbiome through like a stool sample, but we're just not quite there yet. And so sometimes, this is the rare case in my world, somebody would come to me and say like, I tried this probiotic, And I feel really confident that it's helping me and I feel a lot better. And I'd be like, this is, that's great. My bad.

Placebo or otherwise.

Yeah, I think that when that happens, I'm happy for them because pain is difficult to treat, right? And actually the placebo effect, it's great for pain if it's affecting the pathways in your brain. So I don't rip it from people's hands, but I will say the most common scenario for me in a tertiary center people have tried and failed a lot of things is that either they will have tried probiotics and they'll fail, or they'll be on a probiotic and I'll say like, look, did this help? Like, how much better do you think? And they'll say, honestly, now that you're asking, I don't know that it's doing anything. And I think if you don't know, then it's helpful to just look at the data. Actually, for everyone, it's helpful to look at the data, which is that formally the American Gastroenterological Association does not recommend probiotics for most indications. Like, we do for very specific things like pouchitis, for example, and inflammatory bowel disease, but the data's not there. And one area I, you know, that's very close to my heart is like, well, what about probiotics or even something like fecal transplant for Parkinson's disease? Because like with a lot of diseases, we know that there are these different—

You got to slow down a little bit. You just mentioned fecal transplantation for Parkinson's disease, fecal microbial FMT. And I think a lot of our viewers right now are going to raise their eyes and pay close attention to what this is all about.

Yeah.

Why would there be any justification for the consideration of a fecal transplant from a not, uh, a healthy individual to one who has a Parkinson's diagnosis?

Yes. Okay. So let's take a, a big step back. So fecal transplant is this idea. So we've talked about probiotic supplements where you might take a capsule, for example, that's the most common thing that's supposed to contain live bacteria. The data's not great universally for, for most conditions. But fecal microbiota transplant is like taking this idea of changing your microbiome even further by saying, we're going to, in some form, and there's different ways to do it, but we're going to insert the microbiome of another person who maybe has the condition that you want. Maybe they're just a healthy person and you have some disease state that we think could be improved if we change your microbiome like this. The way that we do this in the hospital is like, we'll take you for a colonoscopy. And this is gonna sound so silly, but it's really as simple as like, we just spray the poop of somebody who's a healthy donor into you. And that works really well for conditions like C. difficile infection, which is this bacteria that can cause a really horrible infection. FMT, fecal microbiota transfer, works really well there because in certain conditions, metabolic disease, Parkinson's disease, we've seen these associations where there seems to be a change in the kinds of species, the proportions of those species compared to healthier people who are maybe the same age, same gender. There's often this idea that, okay, the microbiome has to play a role. And I think we all feel pretty confident that the microbiome is playing a role. We've done so many clinical trials and we, I mean, people in this field, So many clinical trials to try to treat irritable bowel syndrome with fecal transplant, to try to treat Parkinson's disease with fecal transplant, and the outcomes aren't great. People don't actually do much better. That doesn't mean that the microbiome isn't playing a big role. My whole lab is devoted to studying how the gut can influence Parkinson's disease, but I think what it's telling us is that when I describe the microbiome, I think about it as a garden, and— You know, you have these flowers and weeds that grow. And I think sometimes, like for example, in Parkinson's, we might say there's too many weeds, what we want are more flowers. So let's sprinkle a bunch of flower seeds on it. That's what the FMT could do, or maybe that's what probiotics do. And I think the problem with all of these therapies is that the weeds may just be growing in response to something else in the environment that we're not fixing. Like maybe it's because they're not getting enough sunlight. Maybe it's because the pH of the soil is wrong. So just because we sprinkle the right seeds Right. Seeds in there temporarily, maybe those seeds can't grow. They just don't thrive. They don't take in the soil. And I think that's the kind of inherent problem with the way we're approaching it now. Not to say that we shouldn't keep trying, but I just think we're not there. And I think that probably the most robustly studied thing to do is to get to the prebiotics, which you mentioned. So prebiotics are what we are feeding those gut microbes. And so usually, and this is true in anything from IBS to Parkinson's, I say, let's focus on the foods that we're eating and let's focus on how we're— the environment that we're creating for those microbes. And those things, we have the epidemiological evidence for a lot of them at least, and a lot of the mechanistic evidence. Those things we know are linked more strongly to the outcomes, and the data's just better than what we have right now for things like probiotics.

Wow. So you are researching then the gastrointestinal relationship to Parkinson's. That's— it seems like quite a leap, but you know, GI symptoms in Parkinson's have been described for over 100 years. In the original essay by James Parkinson, it wasn't really mentioned, but I think, you know, more recently it has been. And I think, you know, some really interesting things were discovered over the years. For example, the pretty significant reduction in risk of developing Parkinson's in individuals who've had their vagus nerve cut, you know, years ago. Yes. So in my day, my dad used to say that, now I'm saying it. Uh, back in my day, uh, for ulcer treatment, it would be a vagotomy pyloroplasty. In other words, operating on the pylorus and cutting the vagus nerve, i.e., cutting what was thought to be the cause of the excess acid before H. pylori, you know, was identified. So there became this group of people who underwent vagotomy, had their vagus nerve cut, and when you follow them, they had a significant reduction in risk for developing Parkinson's. What did that tell us? Well, the interpretation was one that said something is going up the vagus nerve and making its way into the brain. Maybe it's the precursor for this misfolded protein or alpha-synuclein. But, you know, beyond that, the, the idea of a fecal microbial transplant as a, a way of helping a Parkinson's patient, I think, targets the fire, not just the smoke, as a treatment. In other words, We have pretty good treatments for rigidity and for tremor and for constipation in the Parkinson's patient. They're very valuable. There's no one that would say otherwise. But we're not treating the underlying issue, which is the degeneration of those dopaminergic cells in the substantia nigra, until this year. Well, calendar— not this calendar year, but in April of 2025, published in the New England Journal of Medicine was a powerful study, uh, the first of its kind, that looked at treating Parkinson's patients, a group of 130 patients, with a GLP-1 agonist, Ozempic-like drug. And they stopped the disease dead in its tracks in terms of its progression. For me, that's, that's a game changer. What did it do? It targeted metabolism And we know that there's pretty good research suggesting that metabolism is affected by the microbiome. So it really lends itself or leads in very nicely to what you're researching, that the issues related to why fecal microbial transplant might be helpful have to do perhaps with metabolism and the mitochondrial function within the brain in those cells in the substantia nigra. So, gosh, I look forward to hearing more about what you're doing there because I think this could be really very, very exciting if you can demonstrate metabolic improvement in these patients. You know, if you're a type 2 diabetic, you have a 40% increased risk of becoming a Parkinson's patient. Yeah. If you can demonstrate improvement in insulin functionality and glucose tolerance, I think that you're going to really be, you know, supplying one very big piece of this Parkinson's puzzle. We know that, you know, if people watch the episode here with Dr. Ray Dorsey, that environmental toxins, which are threatening to the mitochondrial function of these cells, playing a role. But again, you know, I think underlying all this are the metabolic issues throughout the body for which fecal microbial transplant might, you know, be really, really helpful. Um, we were— I hate, dare I say, promoting, but at least investigating FMT in autism many years ago. And then we're, I think, gratified to see a study, collaborative study, University of Arizona with Dr. Alessio Fasano from Harvard. Yeah, demonstrating significant improvement in these kids, at least in terms of their GI issues, which are rampant in autism spectrum disorder. So very interesting. Let's, let's go back to your book. So how is it that people— forgive me for— we've been— I haven't even got to any of the questions I had written down for you so far.

This has been so great.

We're now 53 minutes into our time together. But you mentioned that people can be constipated and there can be a lot of different reasons. So let's just flesh out a couple of common reasons that people can have difficulty with their bowel movements and they are infrequent.

Yeah, so I think constipation sounds like it's like one condition, one thing, and it actually could describe a lot of different problems going on. So when I'm trying to explain constipation to my patients, I describe it like trying to get toothpaste out of a toothpaste tube. So sometimes the issue is things that are causing us to not— I know, picture it. Stick with me.

I'm there.

Go ahead. So sometimes the issue is you're not Squeezing hard enough, and there's an issue with the propulsion. And maybe it's something that we need to do to augment the muscles of your colon to produce those contractions. Maybe it's related to your Valsalva maneuver that we all do. Maybe it's an issue with the softness of the toothpaste. I call that the pliability. And maybe that's again, like, are we eating enough fiber? Are we drinking enough water? Is there something that the toothpaste itself is too hard, too pebbly? It's not coming out. But a very underappreciated part of the story is the pelvic floor, and that is what I liken to saying you squeezing as hard as you can, but you've not taken the cap off the toothpaste tube. And about one in three people who have what we would call constipation—they've tried different laxatives; they failed to get better with it—the issue is the pelvic floor. And what happens in a lot of people over time is that, for example, maybe at some point in your life. You had constipation for another reason. Your gut was moving slowly, you weren't— you were eating a lot of ultra-processed foods, you didn't get enough fiber, and so you trained your body over time that you had to strain a lot harder to have a bowel movement. And over time, as you strained and strained, the muscles in your pelvic floor started to reshape a little bit, and the, the sphincters got a little bit more toned, and eventually they work against you. Even when later on in life you start to eat more fiber, like you discover legumes and beans and you go vegan, but suddenly now you have this closed door and the cap's not coming off. And so it's very common that people who have been on 2 or 3 different laxatives, once we treat the pelvic floor, then somehow, you know, like often they actually don't need that many laxatives anymore. Maybe they just need one or none. And the issue is not that the whole time. So those are the 3 things that I tell people that we need to investigate. Think about and see which one is the problem. And often, you know, it's like not just one, it may be of 2, maybe of all 3. But until you think about it a little bit more holistically, you might not understand why your friend can take MiraLAX and they do great, but you can take like 6 MiraLAX doses in a day and nothing happens for you. It's because you probably don't have the same thing going on.

What does it mean then we treat the pelvic floor? What do you do?

Yeah, so the It's a kind of good thing. I actually frame it this way. When somebody comes to me and I— we make a diagnosis of pelvic floor, we call it pelvic floor dyssynergia. It's a fancy word to say that the muscles are either paradoxically contracting or they're not generating the right amount of pressure. I actually tell them this is kind of good news because we just treat it with pelvic floor physical therapy. We treat it with a special kind of physical therapy called biofeedback, but that's been shown in studies to be about 80% effective after about 2 to 3 months. So in the scheme of your life, you go to this physical therapy. Yes, it's a little weird. Yes, it's a little awkward, but it's 2 or 3 months of your life for the next several years of not having to take a medication. It's actually kind of like a big win, and it's actually very treatable. Even in my Parkinson's patients, we see this, and we see really good success rates with it.

You discuss in your book the short-chain fatty acids, and We've talked about short-chain fatty acids as a very important product of the, of the gut bacteria that has effects throughout the body. But you, uh, we— you also talk about it in terms of, of anorectal sensitivity.

Yeah.

And how does that relate? I— that, that's news, I think, to a lot of people. I mean, we're trying to boost our short-chain fatty acids by taking a lot of prebiotic fiber, but what is— is this a potential downside?

No, this is an upside. So I think that the beneficial short-chain fatty acids like butyrate have been studied as improving in some ways the capacity— there's 2 different aspects to this, but improving our capacity to sense and respond to stool that's sitting there in the rectum. And that's a big problem for the about 7% of Americans who deal with fecal incontinence. That's a lot of us. And they've done these studies where they found that actually just fiber supplements like psyllium can help improve that sensitivity so those episodes don't happen as often. And we think that they're being mediated by the short-chain fatty acids, which improve the sensitivity of those nerves. There's a different type of sensitivity that we sometimes talk about, which is not what we think happens with short-chain fatty acids like butyrate or others, which is that if the nerve cells that sense pain and send pain signals up to the brain become more sensitized, that would be a bit of a problem. But we don't, we actually think that The short-chain fatty acids have anti-inflammatory effects and don't do that. There are other things that can make that pain signaling worse, but the message here is eat more fiber.

So what is the one biggest myth that you see in your practice as it relates to to bowel movements?

Well, you mentioned this at the very beginning. It it is that people should have one bowel movement a day. Like truly, that is the biggest myth, and I think I know why that myth took flight initially, which is that our colon. Certainly is primed to have a bowel movement at least once in the morning. Every morning, a lot of factors come together that are optimized for a good bowel movement. And that is that your colon actually operates very, very strongly on a circadian rhythm. So unlike a lot of other organs in your body, it almost goes completely quiescent at night. There's very little activity. And in those first 1 or 2 hours upon waking, The nerve cells in the gut have this circadian entrenchment, entrainment. It wakes up and naturally produces very strong contractions that you very rarely are going to get the rest of your day. You're going to get a little bit of it when you eat a meal. You're going to get a little bit of it if you exercise. You're going to get a little bit of it if you drink coffee. And often we're doing all of those things in the morning. We're taking the dog for a walk, we're having our first cup of coffee, and now we've woken up. So it's a perfect time to have a bowel movement, but that doesn't mean that's the only way to live and that's the best way to live. Because what I often tell people, and I'm sure a lot of listeners could relate to this, once you start meeting your fiber goals, you're gonna poop more than once a day. Like, it's, you know, like, unless you are working against it, because it's just a softer, you're gonna have softer stool, which is a really healthy and good thing. So some people will say, I've started eating a lot more fiber and now I have to go to the bathroom 3 times a day. I have diarrhea. This is a problem. I would actually say that's normal. This is like very healthy, and as long as it's not bothering you, like, great. 3 times a day would be considered within the range of normal. Americans think that having a bowel movement every 3rd day or up to 3 times a day could be normal. So, so you're not weird if you're going after every meal. That's actually like your own body. It's called the gastrointestinal reflex.

You can still be weird for other reasons.

You can have lots of reasons, but it's not going to be that.

How can someone improve their bowel movements immediately?

Stop taking your smartphone to the bathroom, guys. Not good for you. It can increase your risk of hemorrhoids. I know, I know that's a hard message to hear.

Okay. Okay. Um, okay. Here's the next question. If listeners want to have one important message about the gut-brain connection, what would it be?

It would be to start treating your gut like a brain. And that means showing it the same respect you show the brain in the head and thinking really carefully about all the junk that you put inside your body because it's hitting

Dr. Petriccia, thank you for spending time with us today, and congratulations on your book. Somebody had to write this book, and you did it. So—

I appreciate you.

No, you really did. And I can only imagine, you know, what it's like to be— well, I don't have to imagine. I know what it's— when I wrote Grain Brain, I got a lot of pushback. But thank you for doing this, and I think all of our viewers are really We're going to appreciate it. Thank you. grateful for the time you spent with us today.

This was a delight. Thank you for having me.

All right. Hope to see you soon. Dr. Pasricha, thank you for breaking the long-held silence about a topic that affects really every human being, yet is so rarely discussed, with the clarity and compassion that you brought to our podcast today. You know, your work reminds us that gut-related symptoms are not all in our heads, but neither are they separate from the brain. They are fully integrated. You know, this gut-brain connection is actually very, very real. And understanding that integration may be one of the most powerful tools that we have for improving not just brain health and gut health, but overall health as well. So for everyone listening, I highly encourage you to read the book, You've Been Pooping All Wrong. Maybe you have, maybe you haven't, but it's still worth reading. This is a science-based, practical, and surprisingly liberating read. Thank you for joining us today on The Empowered Neurologist. I'm Dr. David Perlmutter, and we will be back soon. Bye for now.