CEimpact Podcast

Understanding the Gut-Brain Connection Part I

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The gut and brain are in constant conversation, influencing everything from mood and motivation to digestion and hormonal health. In this episode, we unpack the fundamentals of the gut-brain axis, including the role of the microbiome, common medications that impact gut health, and how those changes can ripple into mental well-being. Tune in to build your foundational knowledge and start recognizing how pharmacy practice intersects with the gut-brain connection.

HOST
Joshua Davis Kinsey, PharmD
VP, Education
CEimpact

GUEST
Lara Zakaria, PharmD, MS, CNS, CDN, IFMCP
Owner, Founder
Foodie Farmacist LLC

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CPE INFORMATION
Learning Objectives
Upon successful completion of this knowledge-based activity, participants should be able to:
1. Explain the physiological connection between the gut and brain, including the role of the microbiome in mental and neurological health.
2. Describe how some drugs can influence the composition and function of the gut microbiome.

0.05 CEU/0.5 Hr
UAN: 0107-0000-25-153-H01-P
Initial release date: 4/28/2025
Expiration date: 4/28/2026
Additional CPE details can be found here.

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Speaker 1:

Hey, ce Impact subscribers, Welcome to the Game Changers Clinical Conversations podcast. I'm your host, josh Kinsey, and as always, I'm super excited about our conversation today. The gut and the brain are in constant communication, influencing everything from mood and cognition to neurological health, mood and cognition to neurological health. In this episode, we'll explore the science behind the gut-brain connection, the role of microbiome and how pharmacists can help patients optimize both digestive and mental well-being. And to do that, we have a fantastic guest expert with us today, laura Zacharia. How are you?

Speaker 2:

I'm great. Thank you so much for having me.

Speaker 1:

Yeah, thanks for being here. We appreciate you taking time out of your busy schedule to join us today. So, laura, if you don't mind, give our listeners a little bit about. Tell them about yourself.

Speaker 2:

Thank you so much and thanks again for having me and this opportunity to talk about what I think is a pretty important topic. So my background is in pharmacy. I come from several years doing retail pharmacy. I've done everything from corporate retail to independent pharmacy, pharmacy management and I transitioned over to doing functional medicine consultations and I do nutrition counseling. I actually also have a background as a certified nutrition specialist. So basically I'm board certified in nutrition and that really evolved out of my experiences listening and talking to my patients over the years in the community setting.

Speaker 2:

Pharmacists who are in that setting have such a powerful impact because we are not only accessible but we are typically the most approachable healthcare practitioner that our patients have, and in my experience, a lot of those patients are frustrated because they're experiencing symptoms that seem disconnected. They might even intuitively know that there's a relationship or a connection between them, but they seldom have the opportunity to really have an expert help them put together those connections Exactly, and so I'm motivated by helping other clinicians, other pharmacists, learn about the nutrition side of things, learn about functional medicine and whole person care in a way that they can then make it accessible for their patients, and I think that's a huge community impact that we can have together.

Speaker 1:

Yeah, for sure. And you know some would jump on the bandwagon and be like, oh, this is a trend, this is the new trend, like the holistic approach and supplements and whatever nutrition. But I mean it shouldn't be a trend, it should have been a thing all along.

Speaker 2:

Yeah absolutely, and I'm here to ensure that it's not a passing trend that we make it approachable, sustainable and something that really has an impact on our healthcare outcomes.

Speaker 1:

Yeah, that's great, that's great. Well, one of the things that we love to do with our podcast is show how we can impact the community and how we can impact more than just the one patient and whatnot. So, yeah, this is great. Well, thanks again, it's great to have you and we're super excited for you to to share all of your knowledge with us today, and all of 30 minutes You're going to, you're going to impart all your wisdom.

Speaker 2:

We're going to pack it in, that's right.

Speaker 1:

Well, on that note, let's jump right into our first thing we touched on in the title of the episode as well, as gut brain, so we're talking about that connection. So let's let's touch on that first remind our listeners how the gut and the brain communicate, like how do they talk to each other and why is that a thing you know, like what's going on?

Speaker 2:

Absolutely so. One of the most established connections actually in the literature is the gut brain connection. There is multiple points of innervation between the brain and the gut and largely it's related to the ANS autonomic nervous system.

Speaker 2:

So, one of the most famous, that probably has caught most of the trends that we hear about on social media or might be hearing a lot about, is the vagus nerve. Vagal nerve and the way that that connects from the brain to the gut, and that's just one example of the various mechanisms that the brain and the gut are talking to each other, and it's important to also remember this is what's called a bi-directional relationship. This is a two-way highway. This is not some one-way back country road, right?

Speaker 1:

So these are long-time, they, these are all each other.

Speaker 2:

They call each other up. They are on the phone constantly. There are those people. So back in the day, when I used to work at CBS, my best friend worked at another CBS and we would be constantly on the phone with each other, sometimes because we had to call each other to say, hey, did you have XYZ in stock, and sometimes because we just wanted to talk hey how's your day going?

Speaker 2:

what's going on? How's it going right? We were the gut brain connection, right, that bestie that you are calling to make sure that they are on the same page as you. So when we talk about like kind of um, colloquial terms, like uh, I had a gut feeling about this, that is a legitimate brain interpreting what the gut is feeling and sending messages back to the gut. That is part of that two-way connection.

Speaker 1:

I've really never even thought about that before and how that actually like the fear of your stomach dropping and whatever, and that's actually talking.

Speaker 2:

That's actually your stomach in that moment let's use that the butterfly effect. Or when your gut just drops, when something feels really intense, that is actually your brain perceiving a situation and sending the message back to the gut.

Speaker 2:

And if you think about it from a survival mechanism we know sympathetic, parasympathetic, fight or flight, rest and digest. When you think about it in those terms, it makes sense, because the last thing I need when I'm running away from a saber-toothed tiger is to be slowed down because my stomach's like um, excuse me, I need a snack.

Speaker 1:

I'm well hungry. I need to go to the bathroom right now, can we?

Speaker 2:

just take a little pizza, like we don't need those messages, right? Because we're in the middle of trying to make sure that we don't get eaten by that saber tooth tiger. So that back and forth communication is kind of critical. And in this modern life, translate saber tooth tiger to constant stressors. Emails dinging, going off, the messages on your phone are constantly going off. Your boss is breathing down your neck, whatever that looks like for you. That is constantly telling your brain we are not in a safe environment and that's sending messages back down to the gut to then dictate what the gut is going to do with the microbiome environment, with the acidity of the stomach, with the motility of the stool and with how it's going to handle and digest the food that it's introduced Interesting.

Speaker 1:

So I'm learning just already that my brain always says eat, just go eat.

Speaker 2:

That means you're feeling safe. I guess, that literally means that your brain is basically saying it's totally safe, josh, go ahead and have that snack, because we're not running away from anything anytime soon.

Speaker 1:

Just eat that.

Speaker 2:

Eat that ice cream and you'll be fine, yeah but you know how some people, when they're under a lot of stress, they don't want to eat mmm right, some of us stress eat for sure, I'm right. I'm blessed to be one of those people that when I'm under stress, I want to eat but there are definitely there are some people that when they're stressed or certain kinds of stress will lead them to not have an appetite anymore.

Speaker 2:

Right Now the way that you respond to stress. There's a lot of reasons for that. Right, there is. You know how you manage stress, how you perceive stress, what, what access you have to resources to help you cope with that stress, the kind of food that you like. There's a lot of different factors, are different factors that are going to dictate that. But at the end of the day, what's happening is that, depending on the microbiome environment, on the hormones and what's sort of driving that conversation. And then, of course, we know hunger cues are based on things like, yes, insulin, yes, leptin, but also cortisol, serotonin, dopamine. So all of these hormones and these neurotransmitters, the way that they're talking to each other, is going to then send messages back to the brain. That's going to say stressful situation we can eat or stressful situation we can't eat. Obviously, that's very simplified, but you kind of get where I'm going with. The hormonal response is dictated by what's happening in your microbiome and in your gut environment.

Speaker 1:

So so much going on there, but I think the real take home is that they are in constant communication together, the gut and the brain, and they're doing it via multiple different pathways, basically so yeah, so you mentioned microbiome and I think that's a great jump point off to that. So let's, let's jump into microbiome. What, what, what is it, what? What is the role you know? Like? Let's just let's really break it down, okay.

Speaker 2:

I'm going to first tell you what it's not because, I remember being taught you know, whoever y'all out there, you're probably going to be from different generations of pharmacy. So for my older pharmacists that have been doing this for a minute, you might remember being told that the microbiome is just a few different kinds of organisms that live in the gut and that when we take an antibiotic it's going to kill some of them and that's going to increase the risk of candida for some of our patients and we're just going to go ahead and prescribe some lactobacillus or prescribe some probiotic and that's just going to clear it up.

Speaker 1:

I was going to say it's the good bacteria.

Speaker 2:

It's the good bacteria, right, and there's some stuff in there we don't really know what it does. That's what I remember so distinctly hearing. We don't know what it does. This was before you know. This was like at the I'm dating myself now, but like early 2000s, where we were saying, like, okay, just like these wide spectrum antibiotics were hitting the market, we were using them more and more frequently. We're starting to see more antibiotic resistance and, as a result of that, we were trying to figure out is there more to the situation than just some diarrhea and some yeast infections, right? Like? Is that it? Like, do we just give a Diflucan and call it a day?

Speaker 1:

Right.

Speaker 2:

And what we've learned since in the last few decades is that, yes, it is true it's the good bacteria, but it's actually so much more complicated than that. There's actually trillions of little bugs and, yes, there's bacteria, but there's also viruses and there's candida species and there are commensal parasites as well, so it's truly a just mishmash of all these different types of species. Now, yeah we focus a lot on the bacteria, because the bacteria seem to be at the interface of the conversation between the environment, the food that we put inside our gut and what gets communicated then to our DNA and what dictates some of our metabolomics.

Speaker 2:

In other words, when the bacteria in our gut perceive something in the gut or get messages from the brain, they release certain neurotransmitters and certain byproducts that then pick up the phone and they call different parts of our body. So this is why you're hearing a lot more about the microbiome, because in the last couple of decades we've started to realize that the microbiome might actually be yet another almost endocrine system that's communicating, it is dictating transcription in our DNA, it's dictating how our DNA might express, it's sending messages to different organs. It's also communicating to our brain and telling our brain then how to respond to those triggers and those signals. So it's kind of like those old fashioned phone operators.

Speaker 1:

Oh my gosh. Yeah, I was just actually envisioning that, where it's like taking that and putting in and yeah, exactly.

Speaker 2:

And when it's in balance. So when we say good bacteria, the good bacteria has to be in the right balance.

Speaker 2:

There has to be the right species. The species have to be in the right part of the digestive tract, so meaning it also has to be in the right neighborhood. I call it so. When you don't have enough of them, you're missing certain neighborhoods or you just have an overgrowth of things that aren't supposed to be there. That's when we have what we call dysbiosis, or bacterial imbalances, or an over, potentially an overgrowth of bacteria that then causes some of these. That's where we have the problem Exactly.

Speaker 1:

The problem ensues from that.

Speaker 2:

Exactly, exactly.

Speaker 1:

Okay, so that's super helpful as, again, to kind of lay the foundation. And you've talked about how microbiome is involved in a lot of that and it's involved in mood and cognition and neurological and hormonal and all that kind of stuff. So let's talk about medications and or foods, even if we wanted to go down that path that we're introducing, the system that's also affecting I won't even say disrupting, because maybe it's affecting in a good way, absolutely.

Speaker 2:

In fact, let's start with a positive right. Let's start with SSRIs. Standard of care when it comes to depression is the use of antidepressants or SSRIs. What's the mechanism there? Spot check right. They're going to inhibit the breakdown of serotonin. This is operating on the premise that there's an issue with the production and or breakdown of serotonin and that by preventing that breakdown, we're gonna increase the amount of serotonin. More serotonin is going to engage with the serotonin receptor and that's going to enhance mood. Now, real quick, what's one of the side effects like the first thing that you could think of of serotonin, of SSRI rather?

Speaker 1:

Oh goodness, first thing, well, I always think of weight gain, but I don't know if that's it's not for all of them, so I don't know Right, absolutely Weight gain.

Speaker 2:

Exactly GI upset.

Speaker 1:

Oh yeah.

Speaker 2:

Diarrhea. Right, because a large majority of our serotonin receptors actually reside in our gut, because our bacteria actually is part of what's responsible for turning on and making more serotonin, and so to a certain extent we can actually use SSRIs, as it's used sometimes for IBS constipation, because of that improvement in the motility as a result of increasing the concentration of serotonin in the gut. But when you really go upstream, there's something going on in the way that the microbiome is communicating with the innervation signaling from the brain. That's then changing the concentration of the serotonin or changing the way the receptor is engaging with that serotonin, and that's all changing the concentration of the serotonin or changing the way the receptor is engaging with that serotonin. And that's all on that microbiome level right.

Speaker 2:

So one mechanism to enhance this to think about is if you've got somebody who's not doing well on an SSRI, who is potentially still experiencing symptoms of depression and in fact I believe there's a statistic that approximately 40% of patients don't feel 100% better on their SSRI and their depression symptoms continue. So that's a large number of patients that we would never ignore that statistic right. So what else can we do to enhance that? And to me, the obvious next step is to address things that are going to impact the microbiome.

Speaker 2:

And then we're going to introduce the idea that inflammation is one of those drivers of both the disruption in the microbiome as well as the disruption in the communication and the signaling between the gut and the brain that's impacting the outcome of that SSRI intervention.

Speaker 1:

Wow, wow, yeah, and all that's just an SSRI.

Speaker 2:

And that's just an SSRI, and that's just the SSRI. So how many?

Speaker 1:

other medications affect this? No, but what are some of the other common ones that we should look out for as far like? What are we seeing commonly that we know there's evidence that they do affect microbiome or they are affected by microbiome?

Speaker 2:

Absolutely the number one thing is going to be anything that changes the gut environment. So already you know we can think of a bunch of different things right. Top top contenders for me would be PPIs and NSAIDs. Right, but literally anything that is going to alter or have an impact, have an increased risk of bleed as a side effect, anything that has an increased risk of diarrhea or constipation as a side effect is going to impact not only the motility of the gut environment but the pH balance in different parts of the GI, or it's going to have a direct impact on the microflora like antibiotics.

Speaker 1:

I'm also thinking GLP I mean right.

Speaker 2:

Josh, you nailing it Exactly, Exactly. One of the side effects of GLP ones, and why actually it's part of its mechanism, is the change in motility of the GI tract right.

Speaker 2:

So we should be constantly thinking about once we have got somebody on a GLP one, for whatever reason they're on it, we need to be thinking about their gut motility, the environment of the gut and again, what are the alterations? Because we're impacting directly the communication channel to the brain by changing the way the hormones responsible for satiety and hunger are operating. So that's an even more significant impact on their mental health. So, whether they're at risk for it or they come back and they tell you hey, I've lost weight, but I don't seem to have the same. Like you know, my mood is different or I'm not feeling as motivated.

Speaker 2:

We should be diving a little bit deeper and talking to them about their bowel movements, what their gut health looks like. Has their diet changed? Like? That's a really important point actually, because I find, because we're removing the natural hunger cues now we've sort of altered the way somebody thinks about food and the way that they're motivated by food choices. I find a lot of folks, because they're not as driven by that decision, they sort of eat whatever is convenient and they stop thinking about eating in terms of health or even paying attention to the nutrient density. They're just sort of eating because it's convenient, because it's there, because they have to.

Speaker 2:

I've had one patient describe it to me as like, yeah, my husband kind of is worried about me, so he puts down a plate in front of me and I sort of eat it because I don't want him to worry. And that is because the GLP is doing its job. It's really communicating to that person that hey, you don't really need this, you're good, and she's experiencing the weight loss that she's after. But now I'm worried that she's not feeding her microbiome environment with fiber adequately. That tends to be the first thing that falls off of the plate, right, because she feels full. She does. She really doesn't want to eat a whole big salad.

Speaker 2:

She doesn't really have the space for it right so she ends up eating more processed food and as a result of that, she's really not getting as much nutrient density. She's probably not getting a good variety of different colors and anti-inflammatory foods in her diet anymore. She's not getting a lot of protein because again she's feeling satiated and full, and then all of that is going to contribute to some nutrient depletions and it's going to alter her microbiome environment and because her GI has slowed down, that might also impact not only her microbiome her motility.

Speaker 2:

She might experience constipation as a result, and that's going to have its own domino effect of issues.

Speaker 1:

Yeah, you were going to say cascade effect. Yep, exactly, exactly. Well said, yeah. So you also mentioned. You mentioned PPIs, which I think are super common, also over the counter. So I mean, those are something people can grab. You don't have to see them on a prescription screen. That could be something someone's taking that you don't realize. Same with NSAIDs. I mean, very few NSAIDs are prescribed these days, you know, unless they're super high doses, which we'd be worried about as well. But yeah, so anything else that pharmacists can really keep an eye out for as far as if I see a patient on this, I need to trigger the whole idea of you know, let's talk about deeper things, let's see if the communication is there, anything else you?

Speaker 2:

can think of. Yes, one of the most commonly prescribed medications is oral contraceptives. Oral contraceptives alter the GI environment. They also can lead to certain nutrient depletions. I'm going to mention that as well. Right, Particularly B vitamins, but there's also some studies that suggest that things like zinc and magnesium can also be depleted in women who are taking oral contraceptives for an extended period of time.

Speaker 2:

So, definitely something to monitor.

Speaker 2:

But alterations in the microbiome as a result of any HRT, whether that comes from an oral contraceptive or traditional hormone replacement therapy estrogen in particular could alter the microbiome environment because we require the microbiome to actually detoxify and remove those estrogens, otherwise we get an interhepatic recirculation effect.

Speaker 2:

So first it goes through the liver, the liver goes through its phase one, phase two detoxification, then it moves it into the gut, where in the gut we require beta glucuronidation to or beta glucuronidase, the enzyme to perform beta glucuronidation, which is part of that detoxification effect and then puts it in the stool, packages it and sends it out.

Speaker 2:

Right, if you experience constipation or you increase the amount of estrogen net or the stress on removing that estrogen or there are other complications that are impacting the ability of the liver to then do its job to detoxify, that's going to add added burden, added stress. That is going to then essentially speed up that conveyor belt through beta glucuronidase and that is going to also impact the up that conveyor belt through beta-glucuronidase and that is going to also impact the environment in the gut. In fact, we can measure beta-glucuronidase in stool and we can see the impact of the increase of that beta-glucuronidase. That's usually a good signal that there is added detoxification pressure, that there's an altered microbiome environment and likely that there is potentially a recirculation of that estrogen and some estrogen dominance occurring in that case.

Speaker 1:

Interesting. Wow, and again, what else is over the counter now? Birth control pills, right?

Speaker 2:

Those happen to be progestin only. So there's less of an impact, right, so great call out right Less of an impact, that doesn't mean that they're not going to cause their own set of side effects. So still worth the counseling point for sure, but we don't have the estrogen. The estrogen detoxification point is not related there. That said definitely. I mean, it goes back to your point earlier about so many of these things are now over the counter. It only restresses to me the importance of that pharmacist consultation opportunity to pop in and say, hey, what else are you taking?

Speaker 2:

So they're coming in. They're telling you they're filling their SSRI medication. They're telling you they're not feeling well, they're not sure if they should start it. They're hesitant because of X, Y, Z reason. We we have to start asking them what else are you taking over the counter? How often do you take an nsaid? Do you ever take a ppi? Do you have issues with constipation? Are you, are you taking xyz in order to deal with ibs symptoms? Uh, are you on an oral contraceptive right? All of these questions are relevant because not only do they directly impact the microbiome, directly impact motility, directly impact gut health and could potentially alter the way they're experiencing inflammation in their gut, which then potentially has the direct effect on their neurotransmitters, on their hormone function and on their brain chemistry and their brain health.

Speaker 1:

Wow, wow, yeah, that's so much. I mean, again, we've only tipped the iceberg of the common ones. We're not even talking about the ones that are maybe not super common but are still affecting the microbiome and the gut in a specific way. So, yeah, Well, let's jump into some of the opportunities for our pharmacists. So tell us what we could be doing to be better clinicians in this space. What should we be doing? Should we be asking certain questions? You're the expert. I'll let you tell us what we should be doing, because there's so much information here and I feel like we could go in a lot of different directions, but I want to give the listeners you know. Here are a few things you can do and I'll let you go.

Speaker 2:

Yeah, I think I'm going to put it into three categories for us.

Speaker 1:

And Laura, that's a great place for us to stop for today's episode. You've given us some great information to look forward to in part two of the Gut-Brain Connection episode, so, listeners, please be sure to tune in next week for part two. We will learn the specifics about those buckets that Laura mentioned and you'll be able to take some actionable items back to your practice sites. If you're a CE Plan subscriber, be sure to claim your CE credit for this week's episode of Game Changers by logging in at ceimpactcom. And, as always, have a great week and keep learning. I can't wait to dig into another game-changing topic with you all again next week.