The Connection between your Gut and Brain
There is mounting evidence that changes in the gut microbiome (changes in the diversity and quantity of species in the intestines) contributes to Alzheimer's disease.At first glance, this sounds like a logical jump. Gut bacteria are secluded in the intestines. The brain is separated from the rest of the body by the blood-brain barrier. So what could bacteria in the gut have to do with the brain? It suggests an interaction between two (seemingly) heavily guarded parties. Here, I’ll try to convince you of the current evidence that has led researchers to connect the two(1,2).
But first, a background on Alzheimer's Disease
Alzheimer's is characterized by inflammation and the formation of amyloid-beta and tau deposits in the brain. These deposits are misfolded, aggregated proteins. In a sort of chicken or the egg scenario , it's unclear whether these deposits are the cause of problems or whether they are the result of the brain trying to cope with something else. For example, studies that have looked at the removal of amyloid-beta haven’t had the most promising results(3). If amyloid-beta is causing dysfunction, why is removal ineffective? This question remains an issue(1, 2).
What we do know about Alzheimer's is it is associated with several risk factors. A risk factor is something that seems to increase the likelihood of a particular disease. It is not the same as saying that it directly causes the disease. Instead, think of a risk factor as something associated or correlated with a disease that may or may not be causational (no guarantees). It is generally a good practice to avoid risk factors if you are trying to stay healthy.
For Alzheimer's, diet affects your risk. Japan, which experienced dietary changes due to globalization, is seeing increases in Alzheimer's rates. Sleep and dysfunction of the circadian rhythm also contribute. Our levels of activity (the lack thereof) also put us at risk. Even things as random as too much noise too frequently seem to have an affect (1,2).
What we do know about Alzheimer's is it is associated with several risk factors. A risk factor is something that seems to increase the likelihood of a particular disease. It is not the same as saying that it directly causes the disease. Instead, think of a risk factor as something associated or correlated with a disease that may or may not be causational (no guarantees). It is generally a good practice to avoid risk factors if you are trying to stay healthy.
For Alzheimer's, diet affects your risk. Japan, which experienced dietary changes due to globalization, is seeing increases in Alzheimer's rates. Sleep and dysfunction of the circadian rhythm also contribute. Our levels of activity (the lack thereof) also put us at risk. Even things as random as too much noise too frequently seem to have an affect (1,2).
The Microbiome Connection
One fairly strong risk factor that is just starting to be explored might be in the gut. People with Alzheimer's have very different microbiomes (different proportions of species) than healthy people. In the normal gut, there are about 1,000 species of microbes. The gut is composed of a mix of both helpful (lactobacillus, and bifidobacterium) and pathogenic bacteria. As we age, the composition of our microbiome changes (1, 2).
This is a big deal because the composition of microbiomes has connections with a lot of common pathologies including diabetes, obesity, heart disease, and of course, Alzheimer's. We are just now working out why the Alzheimer's connection exists (1, 2).
One possible reason is that when the microbiome changes, it changes both the chemicals secreted in the gut and the response of the immune system. A change in microbiome composition can cause gut bacteria to move into the lymphoid system. That, in turn, increases the permeability of the intestine and the blood brain barrier. This means that the gut and the brain are not impenetrably separated. Bacteria in the gut and their secretions can reach the brain. And in the case of Alzheimer's, they do (1, 2).
Once we accept that bacteria are invading other areas of the body, we need to think about what they secrete. They make amyloid peptides, proteins that contribute to making biofilms, cell-to-cell adhesion, and other interactions. If “amyloid” sounds familiar, it should. The bacterial amyloid is fairly similar to the problematic human beta-amyloid we see in Alzheimer's disease.
We also know Alzheimer's is characterized by inflammation. Bacteria secrete lipopolysaccharides which contribute to neuroinflammation when they are in the bloodstream. Alzheimer’s patients have lipopolysaccharides levels three times greater than healthy people(1, 2).
Sources
This is a big deal because the composition of microbiomes has connections with a lot of common pathologies including diabetes, obesity, heart disease, and of course, Alzheimer's. We are just now working out why the Alzheimer's connection exists (1, 2).
One possible reason is that when the microbiome changes, it changes both the chemicals secreted in the gut and the response of the immune system. A change in microbiome composition can cause gut bacteria to move into the lymphoid system. That, in turn, increases the permeability of the intestine and the blood brain barrier. This means that the gut and the brain are not impenetrably separated. Bacteria in the gut and their secretions can reach the brain. And in the case of Alzheimer's, they do (1, 2).
Once we accept that bacteria are invading other areas of the body, we need to think about what they secrete. They make amyloid peptides, proteins that contribute to making biofilms, cell-to-cell adhesion, and other interactions. If “amyloid” sounds familiar, it should. The bacterial amyloid is fairly similar to the problematic human beta-amyloid we see in Alzheimer's disease.
We also know Alzheimer's is characterized by inflammation. Bacteria secrete lipopolysaccharides which contribute to neuroinflammation when they are in the bloodstream. Alzheimer’s patients have lipopolysaccharides levels three times greater than healthy people(1, 2).
Summary
Here are the main facts covered to suggest a connection between microbiomes and Alzheimer's disease:- Alzheimer's patients have abnormal microbiomes.
- Microbiome changes can cause bacteria to move into the lymphoid system giving it a path to reach and influence the brain.
- Bacteria has been shown to reach the brains of Alzheimer's patients.
- Bacteria can secrete amyloid similar to the amyloid-beta we find in Alzheimer's Disease.
- Bacteria can secrete lipopolysaccharides, which cause neuroinflammation. Neuroinflammation is one characteristic of Alzheimer's. Alzheimer's patients have high levels of lipopolysaccharides .
Sources
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