Gut Feelings: How Your Diet Shapes Your Brain

A healthy brain is crucial for a long, enjoyable life, and growing evidence suggests that the gut plays a significant role in cognitive function. Beyond that, your gut microbiome influences diverse aspects of health, including mood, nutrition, and numerous chronic diseases.

Listen to this discussion with USC Dornsife researchers to learn about how our diet, gut, and microbiome interact to impact the mind and body throughout life.

Moderated by Dana G. Smith '09, reporter, New York Times

With:

• Scott Kanoski, professor of biological sciences, USC Dornsife
• Lindsey Schier, assistant professor of biological sciences, USC Dornsife

Learn more about the Dornsife Dialogues and sign up for the next live event here.

Transcript

00:00:00:19 - 00:00:27:12
Unknown
Welcome back to the Dornsife dialogs as we kick off the new academic year. Those of you who tune in frequently might be thinking something seems different here, and you would be right. I am on the JHA and I am serving as the interim dean of USC Dornsife. While Dornsife might be in a time of transition, we continue to push full speed ahead on our research teaching and signature programing for our extended Dornsife community.

00:00:27:15 - 00:00:50:18
Unknown
Our event today, as always, will offer research insights that may change the way you think, and today in particular, might help you think even better for years. We've been told that the keys to brain health are the Sunday crossword puzzle and fish oil. But the latest science suggests that the secret to a sharp mind could actually be your gut.

00:00:50:21 - 00:01:11:07
Unknown
That's right. The same guy. You might be indulging right now if you're part of our lunch hour livestream as a direct line to your brain. They're in constant conversation through researchers call the gut brain axis. I know, I know. It's easy to think this is the latest clickbait. One day we hear that a nightly glass of wine is how you live to 100.

00:01:11:09 - 00:01:39:28
Unknown
The next we hear that heart failure is just a sip away. But this brain gut connection is now well-established. And their chatter has a huge impact on our overall health. Our expert panel will help us understand this link, revealing how your stomach so called second brain influences everything from your mood to your memory. We will also hear about which foods can supercharge your brain health and why your gut feelings matter more than you think.

00:01:40:01 - 00:02:04:29
Unknown
So let's get started. Our moderator is Dana Smith. Dana is a reporter for The New York Times. Known for her insightful articles on mental health, neuroscience and wellness. Her work has also been featured in Scientific American, The Atlantic, The Guardian, and NPR. Dana earned her Ph.D. in experimental psychology from the University of Cambridge, and she's one of our own.

00:02:05:04 - 00:02:27:09
Unknown
A proud USC Dornsife alum with a bachelor's degree in psychology. I'll hand it over to Dana, who will introduce our panelists. And I'd like to thank everyone once again for tuning. Welcome, everyone. Thank you so much for joining us this afternoon. I think we're going to have a really exciting conversation about how the gut influences the brain. With us today, we have Dr. Scott Karnofsky.

00:02:27:16 - 00:02:58:02
Unknown
Dr. Karnofsky is a professor in the Department of Biological Sciences at USC who studies the neurobiology of obesity onset treatment and pathophysiology. His NIH funded research focuses on how gut to brain signaling affects memory and cognition by the microbiome and the vagus nerve. Additional areas of this research program include understanding how gut and brain derived peptides influence appetite control and unraveling the mechanisms via which early life diet influences brain and cognition.

00:02:58:05 - 00:03:35:05
Unknown
Dr. Kanjorski has held leadership positions in premier scientific societies, including the Society for the Study of Ingested Behavior and the Obesity Society. He is presently the co-director of the U.S. Obesity and Diabetes Research Institute. Also with us today is Dr. Lindsay Shear. Dr. Shear is an assistant professor of biological sciences at USC and a neuroscientist by training. Her NIH funded research program broadly focuses on understand how the chemicals in the foods and fluids that we consume, such as nutrients and toxins, are sensed at critical processing sites in the body, including for the taste system and in the gut.

00:03:35:08 - 00:03:56:25
Unknown
And how this information is signal to the brain to influence our dietary behaviors, what we eat and how much we eat. A second aim of Dr. Sherry's research is to determine how the diet itself impacts these gut brain sensory systems across the lifespan, especially during vulnerable, vulnerable periods of development to produce lasting effects on food choice and in turn, health.

00:03:56:28 - 00:04:20:05
Unknown
Dr.. Can I ask you, Dr. Shear, thank you so much for joining us today. So I guess just to get us started, you know, the gut and the brain seem like really separate organs. How are they connected? What's the evidence that one can actually influence the other? Yes. Thank you for the introduction. And yeah, I guess just kind of take a step back.

00:04:20:05 - 00:04:54:11
Unknown
Survival really depends in large part on our ability to extract nutrients from the environment for energy, but also for the health and maintenance of all the cells in our body. And we have to do that while also avoiding potential toxins in our environment. So many animals, including humans, have evolved really intricate and strong pathways of communication between the organs that are at the front lines of this stomach or intestines and the brain to coordinate all of the events that will make this possible.

00:04:54:13 - 00:05:16:15
Unknown
The biggest nerve is really the major nerve that connects all of these our vital organs, but includes the heart, the lungs. And relevant to this discussion, the gastrointestinal tract, the brain, the vagus nerve is primarily a sensory nerve, meaning that it's sensing what's going on in these organs, how much food is coming in, what types of foods are coming in.

00:05:16:18 - 00:05:53:26
Unknown
And it's providing that rapid information back to the brain. So the brain can then in turn process this and send information back sort of what how to respond to that. For instance, slow digestion, increase digestion rates and so on. So there are other signals that connect the gut brain to, for example, there are hormones that are released from the cells that line the gut, and those can also engage with the vagus nerve and they can travel through the bloodstream to interact with other organs that are off more distant sites, and that includes the brain.

00:05:53:29 - 00:06:17:02
Unknown
And so this whole thing sort of forms a very intricate network of communication that enables the brain to keep tabs on what's happening in the body, the body's physiology, physiology, and then adapt and respond in ways that promote health and well-being.

00:06:17:05 - 00:06:40:05
Unknown
Great. I mean, it seems most intuitive that the gut in the brain would communicate, you know, how hungry or how full we are. So what are those messages and how are they contributing to our weight? Thanks, Dana, for the invitation, the opportunity to join the conversation. But Lindsay mentioned the vagus nerve, which is a primary conduit of communication between the gut and the brain.

00:06:40:05 - 00:07:06:06
Unknown
And one of the signals that is communicated through the vagus nerve that tells us that we're full is when the stomach distend. So when our stomach expands and we're eating food, this signal is sent to the brain through the vagus nerve. And this contributes to us becoming full and eventually terminating a meal. What Lindsay also mentioned is that we have a variety of hormones that are secreted from specialized cells in our intestines and in our stomach.

00:07:06:08 - 00:07:32:15
Unknown
Most of these hormones contribute to us becoming full, leading to a process called satiation or meal termination that we may talk about a few of these throughout the conversation, but they include colleagues, kind in glucagon like peptide one. Both of these will slow the rates of partially digested food transit through our intestines. And this leads us to become full and want to stop consuming food.

00:07:32:15 - 00:07:54:09
Unknown
Although many of you are probably potentially eating during this conversation and might be at the early stage of that meal and are not yet getting those satiation signals. And there's also one of my favorite hormones called ghrelin, which is secreted from specialized cells in the stomach. And this hormone is is unique in that it actually contributes to us feeling hungry to want to initiate a meal.

00:07:54:11 - 00:08:18:20
Unknown
And its release is quite complicated. But one of the components that leads to grow and release is based on meal anticipation. So if many of you are about to start a meal, you may have ghrelin being released from these cells and getting into circulation and eventually talking to the brain and telling you that it's time to eat. And I'll just I was just going to add to that.

00:08:18:22 - 00:08:40:18
Unknown
You know, you focus so much on the signals that stop the meal, but most of us really enjoy eating, and that's because our brain is really hard wired to derive pleasure from food. And so on a conscious level, we think about this in terms of how food tastes. Is it really sweet or salty? The sort of enjoyable enjoy a bowl, palatable sensations.

00:08:40:25 - 00:09:03:21
Unknown
But there's a lot going on subconsciously too. And that includes from the gut. And so as certain foods are being processed there, they engage many of these same sensors and other signals along the gut that transmit signals to the brain's reward areas. These are the areas that tell us to keep eating. And so maybe if you're early in your lunch, that's those are the signals you're getting now.

00:09:03:24 - 00:09:25:24
Unknown
And fats and sugars are really especially good at engaging these reward pathways. And not only are these signals happening in real time, but they can also which can promote overeating in a meal and maybe encourage you to make room for dessert. But they also happen over the long term and shape the way we eat over over the over a lifetime.

00:09:25:26 - 00:09:56:15
Unknown
So the brain is sort of tracking this type of positive feedback. It remembers when you eat something nutritious, foods that engage this reward pathway and uses that to guide your appetite or your decision about what to eat in the future. So we gradually find these rewarding foods more and more appealing, and we'll seek them out even. And so I think this is partly what makes it very difficult for us to steer away from foods that might be unhealthy when you're consumed in excess.

00:09:56:17 - 00:10:22:23
Unknown
Dr. Aronofsky You mentioned the glucagon like peptide one or glucagon like peptides. And we're hearing a lot about GLP one agonists these days, like Ozempic and Munjal for weight loss. How do these drugs work to reduce those feelings of hunger? Great, Great question, Dana. So GLP one is a hormone that we have indigenously produced in our body and it's produced from the distal intestine.

00:10:22:23 - 00:10:43:00
Unknown
So we have specialized cells that secrete GLP one during a meal and that contributes to the slowing of the transit of nutrients through the GI tract and leading us to become full indigenously. It has a very short half life, which means it doesn't last very long in circulation. So it contributes to feeling full while eating, but it doesn't stay in.

00:10:43:00 - 00:11:11:13
Unknown
The circulation was degraded within a few minutes after its release. So just giving someone GLP one would not be an effective pharmacotherapy for appetite control and weight loss because it's it's very short acting. However, pharmaceutical companies have developed modified versions of GLP one agonist that have a much longer half life. So the first generation ten plus years ago would have about a 2 to 3 hour half life in.

00:11:11:13 - 00:11:35:02
Unknown
These compounds were given twice a day for diabetes control and in some cases for weight loss. A next generation had a longer half life of about 12, 13 hours. So these were given once a day. And as many of you may know, the current generation of GLP one agonist and coagulant just have a half life that's quite long and and are injected in many cases once per week.

00:11:35:04 - 00:11:58:27
Unknown
And what this is doing is it's essentially making the indigenous GLP one system on full speed all the time. So these these drugs are lasting a very long time and this is mimicking what GLP one is doing from the intestines to slow the rate of partially digested nutrients through the GI tract. Another interesting thing about the GOP one system is scope.

00:11:58:27 - 00:12:26:20
Unknown
One is produced in another place in our body, and that's in the brainstem. So there's a set of neurons in our brainstem that make GLP one and they communicate throughout the brain and they do very similar things to the intestinal JLP one in that they contribute to us becoming for meal termination, but also can reduce reward processing because the receptors for G.O.P. one are expressed in our brains means the limbic reward system.

00:12:26:22 - 00:12:50:20
Unknown
And with the GOP one agonists that are used for diabetes control and weight loss, they're acting on the receptors in the periphery, but they're also getting in to the brain. So very much of what is happening, how these drugs are effective involves getting into the brain from the blood and acting on top one receptors in the brain to contribute to feeling full and potentially to make things less rewarding.

00:12:50:23 - 00:13:20:01
Unknown
And because of that, there's some interest in whether or not these drugs may have some efficacy for treatment of substance abuse disorders. But the research on that front is in its infancy at this point. What about other mental health conditions? You know, is there a link between the brain and, you know, depression or anxiety, for instance? You know, is the gut influencing other aspects of our mental health?

00:13:20:04 - 00:13:45:08
Unknown
Yeah, I think, you know, we know from from human fMRI studies that the activity of the gut and the hormones that are produced there, the signals that are coming up through the vagus nerve and other nerves are really processed in nearly every major part of the brain. So really meaning that these events can impact many different things, how you're feeling, your mood, the decisions that you're going to make, moment to moment.

00:13:45:11 - 00:14:15:08
Unknown
And so I think there's high potential and emerging evidence that what's going on in the gut can influence other aspects of brain function and anxiety and depression are really complex conditions. So they probably have very complex etiologies or causes and so it can kill the vagus nerve being the major nerve that connects all of our internal organs to the brain.

00:14:15:11 - 00:14:50:04
Unknown
The FDA has approved vagal nerve stimulation, which involves a small implantable device onto the left vagus nerve that can trigger electrical pulses in this nerve and send that triggered that electrical stimulation to the brain. And this is been approved for treatment of depression in certain individuals. And these devices are actually first developed to treat epilepsy and it was noticed from those patients reports and from their clinical researchers looking at them that they were noticing parallel improvements in their overall mood.

00:14:50:06 - 00:15:21:09
Unknown
And so later, studies in humans with major depressive disorder confirmed that that this this type of stimulation of the vagus nerve reduced those depressive symptoms in many of these individuals. And I think we're still trying to understand how this works. As I mentioned, it's the biggest nervous connected to very various parts of the brain. But at least on one level, it seems that vagal nerve stimulation can increase serotonin levels in the brain.

00:15:21:09 - 00:15:45:24
Unknown
And so serotonin is one of the brain's feel good chemicals, if you will. And it's oftentimes found to be low in individuals that have depression. And so stimulation of this nerve can maybe rescue production of this really important neurotransmitter. So that's just one theory. And as I said before, it's pretty complex. And there's likely other factors at play.

00:15:45:26 - 00:16:16:13
Unknown
And we know just sort of also in terms of anxiety, that that activity in this nerve is linked to anxiety. And this maybe is a little bit more complex, you know, from animal studies, for example, that stimulating the vagus nerve can reduce anxiety like behaviors or feel fearful responses. But there's also evidence that if you remove signaling through this pathway that you can eliminate anxiety responses in these animal studies.

00:16:16:15 - 00:16:47:03
Unknown
So this is really probably more a matter of intensity. So certain level of activity along this pathway is is good, maybe provides vigilance in environment, but too much can be very stressful potentially and not enough in sort of dramatically reduced anxiety. So I think this will be really important to kind of consider as this maybe becomes a potential treatment for anxiety disorders in humans.

00:16:47:03 - 00:17:15:13
Unknown
I don't think the science is quite there yet, but there's I think there's a lot of promising pre-clinical data out there that supports these two things can be linked. That's fascinating. What about cognitive health? You know, is there evidence that our gut is also influencing like our memory or cognition or even a risk for dementia? Yes, actually, there is.

00:17:15:13 - 00:17:36:14
Unknown
It's very new emerging evidence, but there's a brain region called the hippocampus, which is very famous brain region in neuroscience. It's important for specific types of learning and memory processes. So one example is if you think about our lunch yesterday, thinking about where we were, who we were with, what we were doing, the hippocampus is important for remembering those kind of episodes.

00:17:36:14 - 00:18:01:25
Unknown
It's also critical for navigating through space, for knowing where something is located, for remembering where you park your car, for example. And there's been recent evidence largely from preclinical animal models suggesting that there's a connection between the gut and the hippocampus through the vagus nerve. So the vagus nerve doesn't communicate directly to the hippocampus, but through sort of a multi synaptic pathway.

00:18:01:27 - 00:18:34:14
Unknown
It does seem to be promoting memory function and hippocampal function in preclinical animals. The evidence for this comes in many ways, but in one instance, if you've damaged the vagus nerve, animals start to have problems remembering hippocampal dependent types of learning and memory processes. There's also some evidence that is consistent with this in humans. So the hippocampus is not just important for memory, but it's also one of the first brain regions to be impaired when it comes to Alzheimer's and other types of dementia.

00:18:34:16 - 00:18:58:05
Unknown
And in some cases humans used to get forgotten these, so they would get the vagus nerve at the level of the gut removed to help with ulcerative colitis. And in populations that had this, it's been shown that if you had the got to for colitis there's an increased risk of of dementia. So there is some evidence out there in humans but it's it's very new and it's just emerging at this time.

00:18:58:07 - 00:19:23:10
Unknown
On the flip side of that, Lindsey was mentioning vagal nerve stimulation. So as she mentioned, this has been approved already for depression and epilepsy. There's also an FDA approved vagus nerve stimulation device for for weight loss and for obesity. And there's some interest in whether VNS, the acronym for VAGAL nerve stimulation, can be efficacious in dementia And other syndromes where there's cognitive impairment.

00:19:23:13 - 00:19:51:11
Unknown
And the preclinical evidence from largely from rodent models is consistent with that. So if you have a bagel nerve stimulation in a rat or a mouse, this can promote plasticity in the hippocampus, which is a way that neurons form memories. And there's also evidence in transgenic models of Alzheimer's that a tangled nerve stimulation device may have efficacy for attenuating the negative pathology associated with Alzheimer's in these animals.

00:19:51:19 - 00:20:29:22
Unknown
So this is a very new and emerging area of research, but there is some promise that we may be able to influence memory impairments and dementia through through the gut. And just one more example I was talking about GLP one previously. GLP one also has receptors in this hippocampus brain region and there are some clinical trials being conducted currently to try to look at whether there's any efficacy of the GOP on analogs that are currently used for diabetes and obesity in conditions like mild cognitive impairments and even the early stage of Alzheimer's.

00:20:29:24 - 00:20:50:24
Unknown
So we've talked a lot about the vagus nerve about peptides, but you know, we can't talk about the gut without mentioning the gut microbiome. So can you tell us a little bit about kind of what that is and how that's also influencing our brains? Yeah, so so the gut microbiome is it's essentially a colony or an ecosystem of microorganisms.

00:20:50:26 - 00:21:24:00
Unknown
Those would be viruses and fungi, but mainly bacteria that inhabit our intestines. And so our our understanding of this colony is really in its infancy. And I would say it's really within the last two decades, thanks to many technology, ethical advances in the field that we've been able to learn about what these microbes are and what they do in the gut and the intestine is is sort of home to the largest colony, I guess, in the human body.

00:21:24:00 - 00:21:51:14
Unknown
And it's host trillions of microbes. And in fact, this is sort of a statistic that really impresses me, that there's we have far more microbial genes in our bodies than we do of actual human genes. So they really are a major part of us and they play really important roles in our health too. So they locally, they help us digest the foods that we can't digest very well, such as fiber.

00:21:51:16 - 00:22:18:13
Unknown
But they also can help to maintain the integrity of the intestinal surfaces. So that helps prevent, you know, sort of toxins and other things from getting in. And emerging data suggests that they can influence lots of things about the host's physiology, metabolism and other aspects of immunity. So this is, as I mentioned, a new field, and we're learning more and more about what these things are doing.

00:22:18:13 - 00:22:47:01
Unknown
But it's very clear they they have a large influence on our overall physiology and health. Another hot topic that we hear about a lot on the well desk, The New York Times is inflammation. And I'm curious, you know, what is what exactly is inflammation mean when it comes to our guts and how is that influencing our health, you know, both in our stomachs and also in our brains.

00:22:47:04 - 00:23:17:25
Unknown
The microbiome is, as Lindsey mentioned, a very new field of research. So we're really just learning about this now. Prior to 2012, there was essentially no microbiome research. We do know that with regards to inflammation, there are populations of bacteria that have been identified that are anti-inflammatory and there are other populations of bacteria that are pro-inflammatory. So there's this balance going on between bacterial populations that can have different impacts on inflammation.

00:23:17:27 - 00:23:45:22
Unknown
And in when we consume foods that promote weight gain, that are high in sugar and and saturated fatty acids, this can lead to increased inflammation. And in fact, individuals with obesity have chronic low grade inflammation. And the mechanisms through which dietary factors and metabolic factors are influencing inflammation through the microbiome are just starting to to be understood now as being such a new area of research.

00:23:45:24 - 00:24:23:20
Unknown
Lipopolysaccharide is is one endotoxin that has been studied now for many years now, and that is an endotoxin that is a pro-inflammatory very signal that increases inflammation, that leads to a leaky gut. So our gut has tight junction cells that keep things in and keep other things out. And LPs is a drive from bacteria in our gut and diets high in sugar and saturated fatty acids can lead to increased levels of LPs, which can start to chew away at the gut barrier, get into circulation and lead to an overall pro-inflammatory state.

00:24:23:22 - 00:24:41:09
Unknown
Right. So, you know, what does it look like to have a gut healthy diet then, You know, what are the things that we know are good for our guts and good for our gut microbiome? And what are the things, you know, like you mentioned, maybe high sugar foods that maybe are causing inflammation and causing us to have got problems.

00:24:41:11 - 00:25:09:17
Unknown
We know more about what's bad than what's good. We know that high sugar diets can lead to altered microbiome that may be functionally connected to metabolic dysfunction, functional and even cognitive impairment. When it comes to what's good to eat, fiber is certainly something that thrives in the microbiome. So the bacteria in the microbiome use fibers, the substrate to create short chain fatty acids, which are actually beneficial for us.

00:25:09:17 - 00:25:39:06
Unknown
So they're a source of energy in the colon, but also get it into circulation and have beneficial effects on our brain and anti-inflammatory effects as well. So a high fiber diet or a prebiotic would be beneficial in terms of feeding our gut bacteria and allowing them to produce good things like short chain fatty acids such as butyrate. Yeah, is there is such a thing as a, you know, brain healthy diet, like should we just be eating tons and tons of fiber?

00:25:39:06 - 00:26:02:19
Unknown
Will that make us smarter or happier? Like what's a way to kind of optimize your diet for your brain health? We know that foods that are high in antioxidants and flavonoids can have beneficial effects on the brain. And certainly fiber's good to consume. But but again, we really know more about what not to eat than than what's beneficial for the brain.

00:26:02:20 - 00:26:28:16
Unknown
And there's a lot of evidence showing that foods that are high in saturated fatty acids and sugars can negatively impact the brain, in particular this brain region called the hippocampus that I mentioned earlier. So this brain region is somewhat of a canary in the coal mine in that it's very the neurons in the brain are very metabolically active, and it seems to be one of the first regions to be impacted by diet and metabolic factors.

00:26:28:18 - 00:26:55:28
Unknown
And high sugar diet, for example, can have a negative impact on the hippocampus, particularly when consumed at least from preclinical animal model data during early life periods of development. What about supplements? You know, there's a lot of prebiotics and probiotics in the market these days. Is that doing anything to influence our gut health and our gut microbiome? Like is that something that you all would recommend or are we not quite there yet?

00:26:56:01 - 00:27:28:15
Unknown
So probiotics are really the products that contain live culture or life microbes such as bacteria. You've probably seen these in yogurts, fermented foods, things like that. And the idea is that you're consuming certain microbes that could alter or influence your gut health in a positive way. And probiotics, which Scott already mentioned, are somewhat different. These are items that are such as fiber that can really help to feed and thus grow, ideally the good bacteria in the gut.

00:27:28:17 - 00:27:59:13
Unknown
The question, yeah, do these, do these things work? I think there's a lot of research going on right now on this topic, but I think the jury is still out and there's really a lot of factors to to consider here on the individual level. So we need to learn a lot more about what types of bacteria are beneficial and under what conditions in terms of other health or gut conditions, how much of these items would really need to be consumed and how they interact with other dietary or environmental factors.

00:27:59:13 - 00:28:24:20
Unknown
So I guess I would say that the short answer would be I think we're just not there yet and we don't really know enough about this to to know, you know, the long term consequences of these things. Yeah, if I could just expand on that. It's important to note that these supplements are not regulated by the FDA. So, you know, take take what it says on the label.

00:28:24:22 - 00:28:48:22
Unknown
There may be some research backing that claim up, but this hasn't been through a rigorous years and some cases of testing and clinical trials, and it's not regulated by the FDA. So it's important to keep that in mind. It's not saying that the science behind the claim for these supplements doesn't exist. It's just saying that as as Lindsay was alluding to, we're just not quite there yet.

00:28:48:24 - 00:29:18:25
Unknown
Another product product that I started seeing on the market. Our tests for gut health are tests for your gut microbiome. What can these tests tell us? You know, is this something that you should be getting at a doctor's office that can really tell you a lot about your gut health and even your brain health or yeah, like what is a microbiome test telling us these data is, yes, these tests are basically what they do is they analyze the types and the numbers of the microbes that you have in your gut through a stool sample.

00:29:18:28 - 00:29:40:13
Unknown
But really, to the best of my knowledge, none of these tests have been FDA approved yet either. And we really don't know how accurate they are. As I mentioned before, in the context of probiotics, there's so many factors to consider and so much individual variability that I think this is going to take a lot more research to kind of nail down.

00:29:40:13 - 00:30:06:17
Unknown
And so they're not really used currently to diagnose any health conditions at all. I think that's a sort of still in our future yet. And if I could add a little bit to that, one of the things that makes this so complex is we can say that this population of bacteria is correlated with some health outcome, but it's not just single populations.

00:30:06:17 - 00:30:35:07
Unknown
What's important in many cases is the ratios of of other bacteria to different bacterial populations. And we just don't know enough yet. These correlations may be indicative of causation, but again, it's not just looking at a single population of bacteria in isolation because they do bacteria, a microbiome interact with each other, and we don't fully understand the nature of those interactions because this is such a new field of research.

00:30:35:10 - 00:31:04:10
Unknown
I think we can have a conversation about the gut and about testing for things in your gut without mentioning fecal microbiota transfers. So what exactly is a fecal transplant? Why would someone undertake this and please, you know, enlighten us, Dana. People are eating. Yeah. So it's sort of a kind of disgusting thing to think about. But but it's important.

00:31:04:13 - 00:31:38:07
Unknown
It's been used in veterinary medicine for decades, essentially mechanism unknown. But it has started to be used more in humans based on this syndrome called C diff colitis. It's C difficile colitis, which is irritation, severe irritation in the lower gut that typically comes after antibiotic treatment. So antibiotics kill all kinds of bacteria indiscriminately and that includes, in some cases good bacteria that help keep C diff, which is bad bacteria in check.

00:31:38:09 - 00:32:04:27
Unknown
And the pharmaceutical treatments for C diff really aren't very effective. And this is a very severe syndrome that can even lead to death in some cases. What is effective and this is again a relatively new development is fecal transfer, which is typically done through a colonoscopy type approach. And this has about a 90% effective rate for C diff and it doesn't have to be to keep recurring.

00:32:04:27 - 00:32:28:17
Unknown
It's it's sort of a one and done in most cases not at all. But it's typically one fecal transfer in from a donor who has healthy bacteria, including the population that keep C diff in check is enough to to cure sea life in many cases. There's also emerging interest for fecal transfer in treating other autoimmune syndromes such as Crohn's disease and irritable bowel syndrome.

00:32:28:19 - 00:33:03:16
Unknown
We're not quite there yet in terms of medical application, but there is certainly promise for having fecal transfer as an effective medical treatment for particularly syndromes that involve the lower gut. I'm sorry to to stay on the topic of fecal transplant, but I just think they're so fascinating. And I understand that you're both, you know, researching this in your lab, you know, beyond kind of the application for CDF, what are some other reasons that people might be or researchers like yourself might be exploring fecal matter transplants?

00:33:03:18 - 00:33:40:05
Unknown
In our research, fecal matter transplants can be useful to identifying whether bacterial populations have causal effects on a particular outcome. So in my laboratory, we study how dietary factors during early life development influence cognition. Later in life. And I mentioned earlier that a high sugar diet can lead to changes in the gut microbiome. And in one case we were able to identify a population of bacteria that was elevated by excessive sugar consumption and that was negatively correlated with memory function.

00:33:40:08 - 00:34:06:24
Unknown
So what we were able to do was then take other animals who had never consumed sugar and enriched this type of bacteria, and we were essentially able to replicate the memory impairments associated with excessive sugar consumption during early life development. So in that case, this approach is using, as it is used as a research mechanism to try to identify what changes in the microbiome are indeed leading to memory impairments.

00:34:06:26 - 00:34:31:19
Unknown
The flip side of that can also be used. So in some cases bacteria are missing or absent after a certain diet manipulation. And that absence may be important for something like learning and memory function. And in that case, rather than enriching that population to produce a bad outcome, this would be sort of enriching that population to reverse it being eliminated from the unhealthy diet.

00:34:31:25 - 00:35:06:15
Unknown
And then you can look at whether that enrichment has a functional impact on behavior or metabolic function. I'm really fascinated by this. Is it possible to alter your microbiome as dramatically just through diet changes, or would it really have to be an fmt to kind of completely wipe everything out and start over? You can change the microbiome certainly from dietary changes, but we just don't know enough about it yet.

00:35:06:15 - 00:35:30:02
Unknown
As we've mentioned, like Lyndsey was talking about probiotics, there's no evidence that the bacteria and use populations in these probiotics actually a colony permanently with with the gut microbiome. So you can think of it as yes, your diet can change your microbiome, but it's not as if a single meal is going to have a long term change on the bacterial population.

00:35:30:02 - 00:35:51:19
Unknown
To think about it more of a long term change in diet rather than acute drastic effects from from single meals. Yeah, and I think related to that, we just don't know enough about how much and how long these need to be, how often how much, how long these need to be consumed in order to sort of take hold.

00:35:51:19 - 00:36:30:19
Unknown
So I think that that's a big empirical question out there will be important to kind of further the our understanding about how how diet can potentially reshape the microbiome. We've got some great questions that are coming in from the audience. And just to stick on the topic of probiotics and probiotics, real quick, Dr. Sharon, here's what's the difference between a probiotic and a prebiotic, you know, other than just what it says on the label at the pharmacy, What's actually different in terms of how our gut microbiomes respond or even the types of foods that might contain these?

00:36:30:21 - 00:36:53:02
Unknown
Yeah, so that they're sort of used they're both the goal I guess for both of them would be to kind of influence the, the good microbes that are in the gut to sort of further enhance the good microbes that are in the gut. And but they do this in different ways. So probiotics are foods that actually contain bacteria.

00:36:53:02 - 00:37:29:27
Unknown
For example, other live microbes that as you consume them, the idea is that they will then get into your gut. So these are found in things like yogurts, fermented foods with the hope that they would then sort of colonize and take up residence there and, you know, provide the benefit there. But as we were just mentioning, it's hard you know, it's hard to know yet how well these work because we just don't know enough about sort of the dosing and how much you need and how these interact with other aspects of your diet.

00:37:30:00 - 00:38:00:19
Unknown
And I think Scott made a really important point that a lot of influences on health are based on kind of the ratio of these different types of bacteria in the gut. So Prebiotics, on the other hand, are are items in your food or things in your food that are sort of potentially could benefit or feed the good bacteria in your gut and in that way grow the good bacteria in your gut.

00:38:00:21 - 00:38:40:03
Unknown
So oftentimes these are things like fibers that are very difficult for us to digest, but which the good bacteria can feed on and utilize and will help them sort of stick around and colonize in the gut. So there is this the same endpoint, the same goal, but they do this through different mechanisms. And if I could add a little bit to that, one of the challenges with understanding the connections between pre and probiotics and and gut microbiome is that the fecal content is really not a window into the microbiome that's in our intestines.

00:38:40:05 - 00:39:14:21
Unknown
So the bacterial populations in the intestines are really quite different from what is used for what is basically used for sampling in these test, which is from fecal matter. In preclinical animal models, you can get the microbiome essentially from the intestines and if you sequence it from the fecal microbiome, they're really quite different. And what many people will think is what's more important to health and disease outcomes is, is the bacterial population that are in the intestines and not necessarily what's coming out in the fecal content.

00:39:14:24 - 00:39:36:04
Unknown
We've got a couple more questions about how diet in particular is influencing our health. One, that human is whether the time that we eat makes any difference. And I know that, you know, circadian rhythms have a huge impact on our health. So I'm curious if there's any influence between, you know, meal timing either early in the day, late in the day, you know, some people are doing intermittent fasting where they only eat for a small window, you know.

00:39:36:04 - 00:40:04:03
Unknown
Yeah, there's any research on how the timing of a meal, not just its contents, influences our gut in our brain health. There's really a lot of research on intermittent fasting time or restricted eating and effects on body weight. So can this type of eating be effective as of a weight loss mechanism? And there are some evidence that that these approaches can be beneficial, but the effects are really quite small.

00:40:04:05 - 00:40:31:01
Unknown
So it's not like taking it GLP one analog like Ozempic or Mount Gyro changing when you eat and intermittent fasting is not going to have as large of effects on weight control as at least the pharmaceutical treatments that are available today. But there is there is some research suggesting that there are some beneficial effects of of different eating schedules on on weight control.

00:40:31:04 - 00:40:58:27
Unknown
But again, these effects are relatively small relative to things like GAAP one treatment or bariatric surgery. And then of course, what we have is about the impact of alcohol on our gut and our brain health. And we actually did a story at well, my one of my colleagues did about, you know, alcohol's effect on the gut microbiome. So I'm curious what you all think about that and how it's influencing us.

00:40:58:29 - 00:41:23:16
Unknown
I don't actually know much about that. I mean, I do know that it can influence the the colonies of bacteria in the gut, but I don't know too much about how sort of the broader implications that for for gut health perhaps a related question because it's diving into our reward system and why we like foods that may be bad for us.

00:41:23:19 - 00:41:42:06
Unknown
You know Doctor sure. You talked about how those high sugar, high fat foods really activate that reward system in the brain. Why don't healthy foods to beat that same system? Why aren't we getting that same, you know, response in for a salad or quinoa that we do for, you know, a cookie or a piece of cake? Right. That's that's a good question.

00:41:42:06 - 00:42:14:09
Unknown
It seems like it would be adaptive for for the brain to kind of translate healthier foods into the rewarding ones. But I think, you know, I think about it sort of in terms of an evolutionary perspective, when we were sort of we weren't in an environment where there were so many energy dense foods, high sugar, high fat foods we were searching around for foods and just sources of expedient sources of energy that we could get from our environment.

00:42:14:09 - 00:42:38:18
Unknown
And so being able to find those in the environment, extract those very efficiently from the foods that you're eating. And in order to get enough energy to feed the cells in your body and brain, and then also be able to remember where those types of energy dense foods are, I think that's sort of the environment that these systems grew up in or evolved in.

00:42:38:20 - 00:43:09:16
Unknown
And it's only very recently that we're now in an environment where those things are generally pretty easy for most of us to get. We could processed foods to make them kind of higher in sugar and in fat content. And so so looking at it more recently, it is seems maladaptive, but I think from the long view, it was probably a very adaptive way to be able to look, to locate and prioritize things and find the foods that would that would give us enough energy both immediately.

00:43:09:16 - 00:43:33:11
Unknown
But then in terms of energy to be able to store for times in which there wasn't usable food sources around. So and I agree with all of that. And one thing that I think is important to think about with regards to our attraction to sweet taste is that when our genome evolved, there wasn't fruit juice, there wasn't soda, but there was fruit.

00:43:33:18 - 00:43:56:07
Unknown
And when you consume fruit, you're getting your carbohydrates. But also with fiber as well. So what we've done in modern times of we processed food and we've taken the sweet parts out and added it to different things where it's not necessarily being consumed in the context of having fiber and the vitamins and other beneficial dietary components that are in fruit.

00:43:56:09 - 00:44:24:04
Unknown
Same with lipids. So we have a knack natural attraction to high lipid foods, which makes sense from an evolutionary perspective because there's more calories in fat than in carbohydrates or protein. But again, lipids consumed when we evolved were not necessarily in the form of processed fried baked potatoes, etc. that we consume today with processed foods. I love this question that we just got in and I'm dying to know as well.

00:44:24:06 - 00:44:42:18
Unknown
It puts you to a little bit on the spot. But I'm really curious, you know, how do you think about your diet when it comes to both your gut health and your brain health? You know, there are certain foods that you try to eat pretty consistently or anything that you really shy away from. And yeah, curious how your expertise and your research has influenced your own behaviors, I guess.

00:44:42:18 - 00:45:14:17
Unknown
Yeah. Anecdotally, I mean, I, I do find kind of related to the last question. If I do consume a lot of sugar, sugary foods that I do that does sort of tend to make me feel not not so great a little. And it's I guess lowers my kind of energy or focus, things like that. I don't again, I don't know that there's any science behind that other than that's just sort of my general feeling.

00:45:14:17 - 00:45:41:03
Unknown
And I find that when I kind of reduce that actively and consciously, that that I do end up feeling better now in that way. So yeah, that's just one anecdotal piece of evidence. But some of my friends tease me when talking about our research because they're implying that there's nothing that they can eat, that everything we, we studies showing that there's a problem.

00:45:41:05 - 00:46:17:16
Unknown
That's certainly not true. But there are a lot of dietary factors that I would consume less because of our research. And I'm actually a vegan, so that sounds like a healthy diet. But that said, there's certainly junk food options for for vegan food these days. So that doesn't necessarily imply a healthy diet. But I do try to consume foods that are high in fiber, that are unprocessed and try to avoid heavily processed the term that's used today's ultra processed foods and we have a scale of is a food considered ultra processed versus unprocessed.

00:46:17:16 - 00:46:43:15
Unknown
And there's four levels to the scale. And as much as I can, I try to avoid the ultra processed foods, but occasionally I indulge, as we all do, I'm afraid, or at least as ideal. These next couple questions are a little bit less about the brain and more about how the gut influences other aspects of our health. You know, we talked about inflammation and I'm really curious and it's a great question.

00:46:43:22 - 00:47:19:02
Unknown
You know, how does our gut health influence things like autoimmunity, you know, whether that's, you know, conditions that are specific to the gut or just kind of immune system and immune reactions in general. I'm not really an expert in that area. I mean, there are certain autoimmune disorders that originate in the gut with Crohn's ulcerative colitis, also type one diabetes, where there's impairments in insulin production in the beta cells is obviously connected to, to metabolism and and gut nutrition.

00:47:19:02 - 00:47:51:02
Unknown
But that's not something I'm an expert in. I'll take one more question on to that and again, totally understand if it's not your area of expertise, but there's also a question about gut health and cancer. You know, we're seeing a huge rise right now in colon cancer, unfortunately, especially among younger adults. And I'm curious, again, if there's any research on kind of how our gut health and maybe our gut microbiome influence our risk for GI cancers.

00:47:51:04 - 00:48:25:28
Unknown
I think the links between gut health, microbiome and cancer really get at the inflammation is cancer is very much correlated with with inflammatory pro-inflammatory signaling. And we are beginning to learn about our bacterial populations that can be pro-inflammatory or anti-inflammatory. And I think the connection between cancer is not a direct one, but rather one that's mediated through modulating inflammatory signaling, taking us back to those kind of high sugar, high fat foods.

00:48:25:28 - 00:48:45:18
Unknown
You know, there's a question about craving and the gut biome. You know, is there evidence that kind of like a cyclical effect like you were talking about? Dr. Scheer where, you know, you eat a little bit of sugar and you want more is that do more the response in our brain and kind of target that reward system? Is there something specific about the gut microbes that are wanting more of it and kind of sending us that?

00:48:45:21 - 00:49:09:06
Unknown
And yeah, kind of curious how cravings work when it comes to our gut? Yes. So I think I think there is at least in in animal studies, some emerging data now that there is a link between the gut microbiome and the sort of cravings or the rewarding aspects of food that we have. And the evidence, again, these are really very recent studies.

00:49:09:06 - 00:49:32:08
Unknown
So I think there's a lot more to find out about this. But the idea is I think that the way that these certain bacteria are working can actually suppress, are craving or want for certain types of really palatable chronic foods. So that could be an interesting sort of future direction for maybe how to curb some of these appetites.

00:49:32:11 - 00:49:58:12
Unknown
But I think again, we're not quite there yet, but there's definitely a link there and potentially through alterations in gut brain signaling as one of them potentially alterations of some of these neurotransmitter systems that I was mentioning earlier on. So I think, yeah, I think there's definitely a link and you know, how exactly and what particular types of foods and what aspects of the foods are all open questions.

00:49:58:12 - 00:50:27:05
Unknown
But then in addition to the microbiome, there's also a connection between the vagus and craving. So an animal will press a lever to receive vagus nerve stimulation, or they will prefer to be in a location where they received vagus nerve stimulation. And the pathways have been mapped such that that information from the gut, that signal to the brain through the vagus nerve, then downstream is communicated to the brain reward system.

00:50:27:09 - 00:50:58:25
Unknown
I mentioned the hippocampus as a target of the vagus nerve signaling from the gut, but the missile limbic reward system where you have dopamine produced in the midbrain communicating to reward regions in the brain, is also very much connected to the gut and the vagus nerve. This question is kind of piggybacking on the last one, you know well, where there might not be any research to back it up, but, you know, is there any sense that the things that you're craving are things that your body or your gut actually need?

00:50:58:27 - 00:51:21:28
Unknown
You know, you can I hear this was maybe a theory when women are pregnant that, you know, the things that you crave are actually what your body needs. Is there any evidence for that for I guess the rest of us feel most of the time? Yeah. I think in general it's been sort of difficult to tease out, you know, looking at individual nutrients and things like that.

00:51:21:28 - 00:51:45:05
Unknown
I think there's certain of it there's there's strong evidence for certain cases like salt. When you're depleted of salt, there's a strong you sort of develop a very strong attraction to highly salt foods and fluids in order to replenish that. But when it comes to, like the macronutrient it's that you need the carbohydrates, proteins and the fats in this section for proteins.

00:51:45:05 - 00:52:13:05
Unknown
But that's been a little bit more difficult to kind of find such a strong link. And so one theory is one strategy that the brain or the body is using is to sort of just increase intake of all nutrients or amplify or increase consumption or everything in order to be able to bring in more energy in the form of calories, but also all of these other types of micronutrients.

00:52:13:07 - 00:52:40:20
Unknown
And so protein might work a little bit differently. I think there's when you're missing certain amino acids, there does seem to be an increased like strong attraction for foods that contain the protein. So those amino acids, we've just got a couple minutes left. And one thing I want to ask is, you know, what are you excited about right now in this field?

00:52:40:20 - 00:53:26:03
Unknown
Like, what's really fascinating, you, you know, what are you really passionate in pursuing? Like what's yeah. Most what's most intriguing to you right now in terms of the gut brain connection. I'll start I'm really excited about the connection between the gut and the hippocampus, Alzheimer's and other dementias. We really have no effective cure for this and the connection between the gut and hippocampus as it relates to dementia and Alzheimer's pathology is a very recent discovery, so we don't really understand the mechanisms yet for how the vagus nerve is promoting hippocampal function and potentially ameliorating the deficits seen in dementia.

00:53:26:05 - 00:54:02:26
Unknown
So that's really what I'm excited about right now, just given how there are no effective treatments and this is an emerging biological mechanism that's poorly understood at this point in time. You know, say one thing I'm really interested in the future of and seeing how it unfolds is this idea that we think I think we've tended to think of these systems, you know, the vagus nerve signaling from the gut to the brain or our taste buds signaling about what we're consuming to the brain is really hard wired systems.

00:54:02:26 - 00:54:34:04
Unknown
I think I even call them hardwired systems earlier, but they're really actually shaped by diet. And I guess we didn't touch on that as much as in this discussion. But they are influenced by our diet. And so, for example, the types of taste receptor cells that we express are really influenced by how much sugar we consume or low calorie sweeteners we consume that, and that influences the intensity of that information signal getting to the brain.

00:54:34:06 - 00:55:00:11
Unknown
And a similar thing is happening at the level of the gut where the foods that we're processing, they're actually shaping the sensitivity of that system to the food itself. So that's sort of a future direction of my lab. And there the alluded to, they're sort of vulnerable periods for this potentially early, early in life thing. And where most of the development of these systems are happening.

00:55:00:14 - 00:55:31:26
Unknown
And so trying to understand how the food environment influences things and then know how that influences are eating behaviors throughout life, whether they can be reversed with other types of dietary interventions. So that's I'm going to sneak in one more question Dr. can ask me just because you piqued my interest. I've been reading a lot about dementia, and I'm curious to get your thoughts on, you know, the connection between the Mediterranean diet and potentially, you know, reducing the risk for dementia.

00:55:31:26 - 00:55:56:00
Unknown
Do you think that's through nutrients? Is there something going on with the vagus nerve? They're like, what's the connection between, you know, a brain healthy diet, I suppose, and risk for dementia? I think with the Mediterranean diet, one key component is that there's not a lot of processed foods in a mediterranean diet. It's not targeting necessarily a specific macronutrients, but rather it's more of a a holistic diet approach.

00:55:56:03 - 00:56:24:18
Unknown
There is some evidence, as you mentioned, that there may be beneficial effects for a mediterranean diet on on dementia risk, but those data are not necessarily cut and dry. It's it's an ongoing conversation. I think one of the recent studies looking into this, it was a little bit disappointing, but in that in this type of research, different studies of different findings depending upon their approach and the questions asked, I think it's a little too early to say that.

00:56:24:20 - 00:56:58:05
Unknown
I wouldn't recommend that necessarily based on the evidence today. But that said, a mediterranean diet can be quite healthy if consumed appropriately. Great. I think we're just about out of time. Thank you both so much. This has been an absolutely fascinating conversation and people want to find out more about your research. Where can they find you online? Do you have lab websites or profiles where they find out more about the work you're doing?

00:56:58:07 - 00:57:36:23
Unknown
Yes. So So I have a lab website. It's your lab USC dot com. So find out more about what we're doing there. And I do as well. Can I ask you, ABC.com? Great. And I know that the science is very much a team effort, so I'm always going to give the opportunity to shout out, you know, the rest of your labs for all the work they do, get to keep kind of the science going.

00:57:36:25 - 00:57:58:17
Unknown
Yeah. I mean, I don't spend a lot of time in the lab myself. Really. All of our research is from the very talented undergraduates, graduate and post-doc trainees in the lab. I'm not going to name them all because I have a rather large lab. But there really are very talented young researchers that in my lab and at USC in general.

00:57:58:19 - 00:58:16:27
Unknown
Yeah, same thing, I think. Yeah, they really move the science forward and you can find great. Well, Dr. Chlumsky, Dr. Scheer, thank you so much for sharing your wisdom with us. It's been really fascinating. I think we've all learned a lot and thank you to everyone for tuning in. We appreciate it.