Could the key to understanding Alzheimer’s disease be hiding in your gut? In this fascinating conversation, Dr. Barbara Bendlin, PhD — Professor of Geriatrics and Gerontology at the University of Wisconsin–Madison and a member of the Wisconsin Alzheimer’s Institute — breaks down more than a decade of groundbreaking research on the gut-brain connection.
Transcript:
Jeffrey Snyder, Broadcast Retirement Network
Well, Professor Bendlin, it’s so great to see you. Thanks for joining us in the program this morning.
Barbara Bendlin, PhD, University of Wisconsin–Madison
Thanks for having me, Jeff.
Jeffrey Snyder, Broadcast Retirement Network
And I’m really excited because you and Professor Ray really collaborated on this. And I think, as I was telling you, kind of in the virtual green room, when I think of Alzheimer’s and other cognitive-related diseases, I think about the head, I think about the brain, but based on the research that the two of you did together, as well as the team, the gut, your stomach actually may play a part as well.
Barbara Bendlin, PhD, University of Wisconsin–Madison
Yeah, we’ve been studying the gut microbiome specifically, so the bacteria and other microorganisms in your gut for about 10 years now. And yes, we think that there might be some changes in the gut that can affect the brain.
Jeffrey Snyder, Broadcast Retirement Network
And I know you’ve been doing this for quite some time, and obviously with science, I guess you put forward a hypothesis and then you test it and test it and refine it. So you had to have an inkling that I would assume that this is, that led you to looking at this further. So it wasn’t just connected to the brain.
Can you take us through?
Barbara Bendlin, PhD, University of Wisconsin–Madison
That’s right, yeah, that’s right. So I did this research with a friend and colleague of mine, Dr. Federico Ray, and he’s a bacteriologist. So he was already studying the role of bacteria in health, and particularly in type 2 diabetes and obesity.
And actually some of the factors that we know are risks for dementia. So that got us to thinking if gut bacteria play a role in those conditions, maybe it could also play a role in brain conditions.
Jeffrey Snyder, Broadcast Retirement Network
And it makes sense. I think the more that scientists like yourself, the more research you do, I think the human body, I mean, it has to be interrelated, right? Your brain, your heart, everything is so well connected and it just makes a lot of sense.
And this is really, I think, shaping not only your science, but also research on drugs and other treatments for diseases like Alzheimer’s.
Barbara Bendlin, PhD, University of Wisconsin–Madison
Yeah, I think so too. If we look at pathways that maybe we hadn’t expected previously, that could open up new opportunities for different kinds of treatments that we hadn’t considered previously.
Jeffrey Snyder, Broadcast Retirement Network
So when we’re talking about bacterium, and forgive me, I’m a lay person. I did take biology in 10th grade, but it’s been a while, clearly. But when we talk about the bacterium in the gut, does that come directly from the food that we eat?
Or is that, how does that, what impacts that?
Barbara Bendlin, PhD, University of Wisconsin–Madison
Yes, so the bacteria, humans co-evolved with these bacteria. So we get most of them actually from our mothers when we’re born. So, and if you’re born vaginally, then you actually, yeah, you get a lot of the original microbes from your mother.
And then you accumulate them through exposures in childhood, but probably across the lifetime. And then the food that you eat feeds the bacteria. So everybody has a lot of microbes that live in and on their body.
We think that there’s probably a one-to-one count between microbial cells and human cells. And then the food that we eat, the bacteria are also eating those foods as well.
Jeffrey Snyder, Broadcast Retirement Network
Oh, well, that’s good. They can kind of co-exist. What do they call that?
A symbiotic?
Barbara Bendlin, PhD, University of Wisconsin–Madison
Yeah, absolutely.
Jeffrey Snyder, Broadcast Retirement Network
Symbiotic relationship? I see, I did learn something. If I could ask you, so how does this shape, you know, I’m kind of, I go from point A to point Z.
So I apologize. If you want to talk about points B through Y, we can certainly do that. I want to do that.
But what does this mean in terms of treatment? So kind of uncovering this and doing this work over the last 10 years, does this lead you to perhaps treating the gut first as opposed to some of the plaque that I’ve read about? The tall, if you will, the amyloid?
Barbara Bendlin, PhD, University of Wisconsin–Madison
Yeah, yeah. So I can tell you there’s a couple of pathologies in the brain that define Alzheimer’s disease. One of them is amyloid plaques and the other is a tau pathology.
And there are actually drugs that, you know, research has discovered that companies have made that you can actually now get clinically in some cases. So there’s been a lot of advancement actually in Alzheimer’s disease treatment. So that’s very promising.
I just want to say that, you know, to start that some of the new drugs could be very promising in Alzheimer’s disease. And then what we found is that bacteria in the gut make a small molecule or a metabolite, we call it, called imidazole propionate. And that particular molecule we found out is not particularly good for the brain.
So we found that in people who have a higher level of what we call for short, IMP, when they have a higher level of that in the blood, they have worse cognitive function and they also seem to have more signs of pathology in the brain. So we haven’t developed a treatment to target IMP yet, but we think that that could be a next step, that if you could lower this molecule, that you could then see benefits for the brain.
Jeffrey Snyder, Broadcast Retirement Network
I’ve been reading, and thanks for that, professor. I’ve been reading a lot about, I think, FDA approved drug tests to detect Alzheimer’s disease. Would this be, you know, identifying, since you identified this IMP, you and Professor Ray, would that be another way to confirm?
Barbara Bendlin, PhD, University of Wisconsin–Madison
Oh, that’s a good question. Yeah, so this wouldn’t be a way to confirm that you have a brain disease. So the tests that I think you’re talking about are blood tests that are rather specific to the pathology in the brain.
So for example, there’s a blood test for something called phosphorylated tau 217, P-tau 217, and those particular tests are very, very closely related to the amount of amyloid you have in the brain. And it’s something that we call being sensitive and specific for the pathology. I would say that IMP, which we measured, is more an indicator maybe of a risk for developing pathology.
That’s what we think, at least from these initial studies, because we found, like I said, that higher IMP was associated to more pathology. I hope that makes sense, but it’s kind of the difference between, you know, something that’s directly related to the pathology and something that we found was associated but wouldn’t be like your best marker for brain disease.
Jeffrey Snyder, Broadcast Retirement Network
But it’s part of the big, I guess, and yes, I thank you, that was a very clear explanation. So it’s that even I could understand, but I think it creates the landscape by which the clinician could evaluate somebody, right? I mean, that’s what we’re talking about.
Barbara Bendlin, PhD, University of Wisconsin–Madison
They can look at- That is the hope. That’s actually, yeah, that’s a great point. What we hope with kind of this initial research is that in the future, maybe we could measure IMP in the blood of people.
And if we then had a drug to lower it, that that could potentially be protective of the brain. But I should also mention that, you know, IMP might just be one of many, many things that can affect the brain. So it’s not necessarily the case that if we, you know, in the future, just lower IMP levels, that that would, you know, solve the whole issue.
We think that there’s, you know, a lot of other factors that are involved with development of Alzheimer’s disease pathology.
Jeffrey Snyder, Broadcast Retirement Network
But there have to be other practitioners out there. I would assume that other prestigious universities such as yours that are kind of trying to look at these other pathologies or other areas, right? And so the clinician kind of pulls it all together and says, here’s what everything looks like.
And here’s what we can do.
Barbara Bendlin, PhD, University of Wisconsin–Madison
Yeah, I think, you know, and again, that’s more a vision for the future. I would say that, you know, today for your listeners, if you went to your physician and you said, I would like to have, you know, my IMP measured, they would not do it for you. And this is just very early stages research, but what we would hope is that, you know, maybe in five years, if we had an inhibitor for this, or we had a different way to change the gut microbiome to keep people healthier, you know, at that point, it would be great to do clinical trials and make sure that, yes, this is what we need to do to keep the brain healthy.
So again, these are, you know, early steps. We saw some really interesting findings in people. We did some animal studies, we did some cell studies, and all of those did point towards IMP not being great for the brain.
But, you know, once you develop, say a drug that could treat this, then you need to go through iterations of clinical trials before you’re going to find it in your doctor’s office.
Jeffrey Snyder, Broadcast Retirement Network
So you’ve been working with Professor Ray for the last 10 years on this science. What comes next? Is it, what comes next for the two of you in terms of how do you build upon, you know, I’m really interested in this from a science perspective, what do you need to do in order to continue to refine your conclusions related to IMP, but also maybe find other factors?
Barbara Bendlin, PhD, University of Wisconsin–Madison
Yeah, so we have a larger program of research on gut microbiome. We are really excited about the idea of an inhibitor, and there are other scientists working on that problem. So we would actually like to test an inhibitor in an animal model first, and then maybe that’s something that could eventually come to humans.
But we think that there’s other small molecules that are made by the gut that either might have a good effect on the brain. So that’s an important area of research as well, because we’re not just looking for bad actors, we’re looking for things that could be good in the gut, you know, and are those things that we might wanna increase in people. You know, we’re testing probiotics in some of our research participants, and also considering, you know, different ways that we can potentially change the gut to improve health.
Jeffrey Snyder, Broadcast Retirement Network
And I know you’re at the University of Wisconsin-Madison. Do you get participants from the pool of people around the Madison campus, or can someone who’s watching this possibly apply to assist in the research? I mean, you know, in terms of your testing, how does that work?
Barbara Bendlin, PhD, University of Wisconsin–Madison
So, you know, I’m glad you asked about participants. They’re so important in this work. So in our initial studies, we had close to 2,000 participants who were in the Wisconsin area, who’ve been just so devoted to research and helping us solve the Alzheimer’s problem.
But there are, you know, other ways for any listener to get involved in research. You can look for studies that are close to you. You can also go to a website called clinicaltrials.gov. So if you’re interested in clinical trials, in fact, our probiotic clinical trial is listed there as well. And the Alzheimer’s Association also has a clinical trials match program. So really, no matter where you live, you can get involved in research.
Jeffrey Snyder, Broadcast Retirement Network
Yeah, really important. I would imagine that Wisconsinites, just like North Carolinians, they all have maybe little subtle differences among us as human beings. Might be interesting.
Can I ask you one? This is out of left field, I apologize. Not related directly to the study, but I’m wondering with all the data sets, how does artificial intelligence, or does that play a role in evaluating or screening some of the data?
I’m just wondering how scientists like yourself may leverage the large language model technologies to kind of help with this future research?
Barbara Bendlin, PhD, University of Wisconsin–Madison
That’s such a nice question, Jeff. So we are actually really excited about how AI can help us. One of our projects actually is using AI to essentially prioritize molecules that could be used.
So for example, we have a project where we are looking at various molecules that are safe for human use, and then using AI to see if they work in that pathway that we think leads from the gut to the brain. And so AI could be a really useful tool there because instead of doing all these experiments by hand and testing a lot of things that either A, don’t work, or B, it aren’t safe for humans, is there a way to apply AI to make the whole process go faster? And I’m actually really excited about the potential for AI to speed up drug discovery.
Jeffrey Snyder, Broadcast Retirement Network
Yeah, and I’m sure family members who may have- Absolutely. Family members who may have loved ones who are affected probably do as well. I think that’s how we’re going to get to, you know, I’m not a doomsayer.
I think that, you know, everything has got to get a roll. So Dr. Professor Ben, we’re going to have to leave it there. Really appreciate you coming on the show.
Give our best to Professor Ray. And look, we look forward to having you back on the program very soon.
Barbara Bendlin, PhD, University of Wisconsin–Madison
Thanks so much, Jeff. It’s been fun.
