Connecting the Gut Microbiome to Alzheimer’s Disease

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Transcript

Nathaniel Chin: Welcome to Dementia Matters, a podcast created by the Wisconsin Alzheimer's Disease Research Center. It's our goal to humanize Alzheimer's research so that our community, our patients, our participants at anyone else interested, can get a better understanding of the work that's happening to fight back against this disease. My name is Nathaniel Chin and I'm a geriatric and memory clinic physician at the University of Wisconsin. I'm also the family member of someone living with dementia. I'll be serving as your host for this podcast and asking the questions I believe on the minds of many in our community. Thanks for joining us.

So welcome to Dementia Matters. I have with me here today, Nick Vogt, a MD PhD student at the University of Wisconsin School of Medicine and Public Health. Nick is currently a research investigator with Dr. Barbara Bendlin at our University of Wisconsin Alzheimer's Disease Research Center. He is looking at the gut microbiome as relates to aging and Alzheimer's disease and in fact had a very recent publication and scientific report. I'd like to welcome Nick to the podcast.

Nick Vogt: Thanks for having me.

Chin: Clearly you're interested in human health, but it also seems like your research is going to focus on human health. So then how did you get into Alzheimer's research?

Vogt: Yeah, so I've always been fascinated with the brain and trying to figure out how it works and what I've realized is that I'm also particularly interested in when the brain doesn't work. And Alzheimer's disease is a perfect example of that where individuals lived their entire lives and just as they're about to retire, just as a route to, you know, be able to visit with their grandkids and things like that and spend a lot of time doing that, they're hit with this horrible disease which robs them of their memory and everything like that and really is heartbreaking. And so that's how I've kind of become interested in it.

Chin: And so you've chosen though an interesting focus, at least right now within the Alzheimer's world because as you just said, it's the brain, it's the aging brain, but you're focusing on the gut. So why is that?

Vogt: So for all the billions and trillions of human cells that we have on our bodies, there are also an equal number of bacteria that live in and on us. And so those collections of bacteria are often referred to as the microbiome. And you have microbiomes all over your body, in your skin, in your mouth, and most notably actually in your gut where the majority of those bugs live. And these bugs are really important in these bacteria are really important for a lot of the things that our body does. So when you eat food, the bacteria involved in helping you extract some of that energy for things that you normally couldn't break down. They also make vitamins and they also protect against other bad bacteria overgrowing in those areas. Um, and they're also really involved in educating the immune system too. So helping your body sort of know what's good and what's bad. In the last decade or so, people are realizing that changes in these bacteria in your gut are actually related to a lot of diseases. Some of these diseases make sense, things like obesity, diabetes, insulin resistance. But what people are also starting to realize is that there's this relationship between the gut and the brain and we're seeing changes in the gut bacteria in a variety of neurological conditions, things like multiple sclerosis and Parkinson's disease too. And so we come at this from that perspective and ask the question of are there going to be changes in the gut bacteria in people with Alzheimer's disease?

Chin: Wow. Okay. So I think when you say to the public, bugs and bacteria in our gut, I think that's going to catch a lot of people off guard. So you're telling me that certain bugs are not bad for a certain bacteria are not bad.

Vogt: Exactly. Yeah. There's this really rich interaction between the bacteria in your gut and our bodies and we are really dependent on a lot of these bacteria living in our gut and we've co-evolved with them such that they're really beneficial for us.

Chin: Okay. So then you just had a very prominent publication in scientific report just this year. What did that publication show?

Vogt: Right. So there'd been a lot of indication in some animal studies that if you manipulate the gut bacteria, so if you remove the gut bacteria from animals that are more prone to develop Alzheimer's disease, what you see is that the absence of that gut bacteria actually changes how their brains look in terms of the Alzheimer's disease pathology in their brain, the bad proteins that build up in their brain. And so there some indication that the bacteria in your gut might be related to Alzheimer's disease, but there hadn't been a lot of indication in the human literature. And so that was our primary objective, is we collected fecal samples from 25 participants with Alzheimer's disease and 25 participants who did not have Alzheimer's disease. And we are asking the question of are there differences in the gut bacteria between these two groups?

Chin: Okay. So you looked at people's stool, and you look at people with Alzheimer's, without Alzheimer's, who would be what we consider cognitively normal.

Vogt: Exactly.

Chin: And then you looked for differences.

Vogt: Yeah. And so we take the fecal samples and we can actually extract the bacterial DNA. And that's kind of getting into a little of the details a little bit, but we're using next generation sequencing technology to get a really clear snapshot of what bacteria are in the gut, how many of those bacteria there are, and how are they all related to each other. So we can get this really rich picture of the composition of the gut bacteria in individuals.

Chin: And who would have thought you would find so much information from stool.

Vogt: Exactly.

Chin: But you did. And so what did you find?

Vogt: So broadly, we found that the individuals who have Alzheimer's disease have decreased bacterial diversity in their guts compared to people who do not have Alzheimer's disease. We can also look at how these bacterial communities relate to each other and there's compositional differences between the two groups as well. We can also look at and ask the question of are there any differences in the relative abundance of certain bacteria, so certain species, or certain genera of bacteria in the gut. When we find that from, you know, the species level all the way up to the phylum level, there are broad scale changes in the abundances of certain bacteria in the gut, some of which are elevated and Alzheimer's disease and some of them are decreased decreasing Alzheimer's disease.

Chin: Okay, and so then what you saw was that in people with Alzheimer's disease, they had less diverse bacteria, possibly less abundance of certain good bacteria.  And what does that mean then, what do we do with this information?

Vogt: That's really the big question. It's becoming clear in other studies that look at microbiome changes that this decreased diversity, sort of a common theme throughout. It's seen in obesity and diabetes and Parkinson's disease and now with our study also in Alzheimer's disease, commonly referred to as dysbiosis or this disregulation of the bacteria in your gut. So that kind of fits all into that bigger theme. Also, I should mention that in our study, we also looked at how the changes in these abundances of bacteria related to markers of disease in our participants as well. So we collect a cerebral spinal fluid, which is the fluid that bathes your brain and we can look at certain proteins that are involved in Alzheimer's disease, things like amyloid protein and tau protein, and what we find is that for bacteria that are elevated in Alzheimer's disease, we see relationship between the levels of those bacteria and the levels of Alzheimer's disease pathology in this cerebral spinal fluid, and similarly for those bacteria that are decreased in Alzheimer's disease, we see a decrease in the level of pathology in the cerebral spinal fluid.

Chin: So you have found important associations between certain bacteria and markers, biomarkers that we would check in research for people with Alzheimer's. Not saying one causes the other, but that there's something there. There's a signal present.

Vogt: Yeah. It seems like there's a relationship there. And even more intriguingly is that we also have cerebral spinal fluid on people who are in these cognitively healthy participants as well. And we see that there are the similar relationships even in these people who did not have Alzheimer's disease. So there's some sort of relationship between the levels of bacteria in your gut. And the levels of these bad proteins in the cerebral spinal fluid.

Chin: Okay. And that's why this was such a important publication and really one of the first of its kind. So what is the next step for you?

Vogt: Yeah, so there's a couple different next steps.  One of the important things that we're going to do, and we're just starting to do, is we're interested in looking at how does this relationship change over time. So we're going to collect multiple samples from people with the idea being that if we can show that there are certain changes in the microbiome that relate to changes in the brain, then that would be important to know. The other thing that we're going to do is take this work from the humans into the animal world, which is interesting. So we can. The way that we studied the microbiome and animals is by raising animals under germ-free conditions. So these animals do not have a microbiome. And what we can do then is we can then take these fecal samples that we've collected, give them to the animals to give them a microbiome and see how that changes the disease in their brain.

Chin: So are you proposing to take stool from humans and put it into the colon of a mouse?

Vogt: Exactly. Those are some of our first experiments that we're going to try.

Chin: And so then what do you think, based on what you know now, and I know it's preliminary, but what should people in the community know about their gut microbiome and the aging brain?

Vogt: Well, probably two big things. One is to stay tuned. I think this type of research is we're just scratching the surface on what we know about the microbiome and people are just starting to think about it as turning into therapies. And so that's one of the most important things is to just stay tuned because we're just getting into it. The other thing is that the best thing you can do for your microbiome is to just eat healthy and live healthy. So we don't really know if there's any things that you can take or anything like that, but just living most healthy life is probably the most important thing for your microbiome as well as for your overall general health.

Chin: And that really fits a lot of what we hear which food as medicine and so you're suggesting then as far as having a healthy, diverse microbiome, food is probably our best bet.

Vogt: Exactly, yeah. Eat lots of good things.

Chin: Now, what about people who take probiotics? What would, what do you think of probiotics?

Vogt: Yeah, so that's another active area of research and probiotics refers to specifically isolated strains of bacteria that people take for their health, and I'm not an expert in this area, but basically what we know about probiotics is a lot of them haven't really been studied extensively. And so there are some ongoing studies to see if taking probiotics may lead to health outcomes, but a lot of we just don't know at this point, so it really can't go one way or the other whether we should take them or not. The other thing that, you know, this gets back to our study is that we're finding that a healthy microbiome seems to be related to a diverse microbiome and probiotics are really selected strains, either one or two strains and so that really might not add to your diversity or add to your healthy gut and that's just something to keep in mind as well.

Chin: I think that is an important thing because we think of probiotics as this vast plethora of different bacteria, good bacteria, but what you're saying is that a lot of them really just have one or two of the main species.

Vogt: Exactly.

Chin: So your study in essence though is arguing it's more about this diversity and less about having a lot of the specific one.

Vogt: Exactly.

Chin: Okay. Well, I think that's helpful for our listeners. Is there anything else you want us to know before we conclude?

Vogt: Um, this is an exciting area of research and, and really just starting to really get into it and I think it's going to be something to look at it in the future.

Chin: Thanks again, Nick.

Vogt: Thank you.

Outro: Dementia Matters is brought to you by the Wisconsin Alzheimer's Disease Research Center. The Wisconsin Alzheimer's Disease Research Center combines academic, clinical, and research expertise from the University of Wisconsin School of Medicine and public health, and the Geriatric Research Education and Clinical Center of the William S. Middleton Memorial Veterans Hospital in Madison, Wisconsin. It receives funding from private university, state, and national sources, including a grant from the National Institutes of health for Alzheimer's Disease Centers. This episode was produced by Rebecca Wasieleski and recorded and edited by Alex Wehrli. Our musical jingle is "Cases to Rest," by Blue Dot Sessions. Check out our website at adrc.wisc.edu. You can also follow us on Twitter and Facebook. If you have any questions or comments, email us at dementiamatters@medicine.wisc.edu. Thanks for listening.