In a new field of research, scientists are studying whether microorganisms in the gut may influence brain health and Alzheimer’s. Researchers have found that not only do people with Alzheimer’s have altered gut microbiomes, but bacteria in their gut is also linked to the hallmark pathologies of the disease. Being Patient spoke with Barbara Bendlin, PhD, an associate professor of medicine at the University of Wisconsin-Madison, about her research on the gut microbiome and Alzheimer’s.
- The majority of the human body’s microbes including bacteria, fungi and viruses are in the gut.
- Some scientists have proposed the infectious theory of Alzheimer’s, suggesting that beta-amyloid may be an antimicrobial peptide, protecting the brain from invading microorganisms.
- Researchers conducted a small pilot study by giving participants with Alzheimer’s fecal capsules to examine whether increasing the diversity of their gut microbiome may influence brain health. But the scientists terminated the study as SARS-CoV-2 can be present in fecal material.
Being Patient: What is the gut microbiome?
Barbara Bendlin: Microbes are everywhere in our environment. They include bacteria, fungi, viruses. The majority of [microbes] that are in our body are in our gut. We’re learning more and more about how they are really important for a number of different health conditions. They play a critical role in our health. More recently, we’re also learning that they’re tied to the brain.
For example, the majority of serotonin — a neurotransmitter that makes us feel happy — is actually produced in the gut. There’s a long nerve called the vagus nerve that connects the guts and the brain. So there’s a lot of signaling that happens between the brain and the gut. The area of research that we’re working on right now is looking at the link between the gut and neurodegenerative diseases, and specifically Alzheimer’s disease.
One of the things that we’ve done for a long time is looking at the brain as its own organ, as its own compartment … This idea that the brain is its own thing that’s not interacting with the rest of the body — we can’t do that anymore. We have to think about the brain in the context of the rest of the body.
Being Patient: What’s the link between microbes in the gut and neurodegeneration?
Barbara Bendlin: This is a very, very new field in terms of looking at gut microbiome and neurodegenerative diseases. When I became interested in the topic about five years ago, to talk about the gut microbiome in the context of neurodegenerative diseases like Alzheimer’s disease would be considered pretty fringy.
Some people are still fairly skeptical. And it’s good: We need to be skeptical because the studies just aren’t there yet. But there are more and more investigators who are getting interested in this idea, and [perhaps] one of the first neurodegenerative diseases to be studied in this context is Parkinson’s disease. There is a theory that Parkinson’s disease, which we know to be a brain disease, could potentially start in the gut. That’s because some of the abnormal protein accumulations that you see in Parkinson’s can also be found in the gut. It’s thought that maybe it spreads from the gut to the brain. That’s just one theory.
Being Patient: Are there ways to alter the gut microbiome to improve health?
Barbara Bendlin: One thing that people are studying is actually fecal microbiota transplant, which would be a more radical change of the gut. For example, you might see an alteration of the composition of the gut. A good example is the infection C. difficile where you see this microbe taking over the gut, reducing the diversity and overpowering the gut. The typical treatment for that is antibiotics. But fecal microbiota transplant can actually be used clinically to treat an antibiotic resistance C. difficile infection.
Being Patient: Does fecal microbiota transplant literally involve taking poop pills?
Barbara Bendlin: Yes. And there are different ways that you can do a transplant. You can do it through a colonoscopy or a nasogastric tube. But there are also companies that produce stool capsules, and that could serve as stool transplants to change the diversity of the gut … There’s a lot of studies that are testing this in a number of other conditions, including neurological conditions.
We here in Wisconsin actually ran a feasibility study (fecal microbiota transplant or stool transplant study) to see if this could be used in Alzheimer’s disease. By the way, I should tell everybody tuning in right now, this is not something that we recommend [you doing it on your own] because there could be a lot of other things in stool that you don’t want to introduce. So we used a product that was sourced and was screened.
Now, the idea here is not that you would treat Alzheimer’s disease with stool capsules. The idea is: Could you change the diversity of the gut and see if that impacts the brain, then figure out why that is? So how do we get a handle on how the gut is linked to the brain? And could that be the target of new therapies?
Being Patient: Has the pandemic affected your research?
Barbara Bendlin: A lot of our research studies are still ongoing. With regard to the fecal microbiota transplant study, [it has] ended and that is because the virus that causes COVID is actually present in stool sample. You can screen stool samples for that virus, but we could not rule out 100 percent that the virus may not be present if donor samples were collected recently.
Being Patient: Why may increased diversity in the gut microbiome be beneficial?
Barbara Bendlin: If you think of a healthy ecosystem, there’s lots of different kinds of plants and animals, as opposed to monoculture where you just have one kind of plant. That doesn’t tend to be a healthy ecosystem, and the same is likely true in the human gut.
[In a prior study], after we had compared participants who had Alzheimer’s dementia to people without Alzheimer’s dementia, we found that there were differences in the composition of the gut, but also that individuals with Alzheimer’s disease had less [diversity] of microbes.
Being Patient: Is there any link between the gut microbiome and beta-amyloid?
Barbara Bendlin: There have been studies done in mice. These mice are kept germ free, but in this case, they were Alzheimer’s mice so they overproduced amyloid. What happens is if you keep a mouse that overproduces amyloid, [and] if you keep them germ free, they make less amyloid plaques … If you put them in standard housing with all kinds of microbes, then those same mice will have more amyloid plaque.
That’s a very crude but clear link between microbes and the amyloid plaque formation. In our study, [this link] was more correlative. We were looking at human participants. We did find that there were relationships between gut bacteria and amyloid in the brain.
Being Patient: Why would there be a link between gut bacteria and beta-amyloid?
Barbara Bendlin: One idea is called the infectious hypothesis of Alzheimer’s disease. The idea is that potentially microbes or microbial products could get in the brain, and then amyloid would come in as an antimicrobial peptide. Some people have studied this, and there seems to be a little bit of evidence for it. For example, if you take an animal and you put microbes in its brain, amyloid could come in to almost protect the brain by surrounding that microbe … but we don’t have good evidence yet that microbes get into the brain. There needs to be more studies.
Being Patient: We need to know a lot more, don’t we?
Barbara Bendlin: We do need to know a lot more about Alzheimer’s more generally. We need to come up with a way to treat Alzheimer’s disease as quickly as possible.
With regard to the microbial work that’s been going on, there has been an increased interest. The National Institutes of Health [and] the Infectious Diseases Society of America are putting money towards this. There are smaller private foundations that have been funding this kind of work. I think that it’s actually coming out of the fringe and becoming more common for people to to look at this.
Overall, in the field of Alzheimer’s disease and other related dementias, the doors have really been opened. People are coming at this from all possible angles, and that’s what we really need to beat this disease.
The interview has been edited for length and clarity.
Contact Nicholas Chan at firstname.lastname@example.org