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Gut-Brain Axis
A Twisted Tale of Genes, Microbes, and Alzheimer's
Bacteria are associated with a gene for Alzheimer's. Can we control them?
Posted May 25, 2023 Reviewed by Michelle Quirk
Key points
- Alzheimer's is associated with aging, but also has a genetic component.
- Modifiable risk factors, including diet, may contribute to 40 percent of dementia risk.
- Although the mechanisms are yet to be worked out, a diverse microbiota is associated with lowered risk.
The mystery of what goes on inside the mind of another person becomes terrifyingly impenetrable in the final stages of dementia; twilight to pitch dark at the vanishing line between life and death. ― Nicci Gerrard
According to the World Health Organization, Alzheimer's is one of our most debilitating diseases. It effectively erases who you are, insinuating itself at first with annoyance, then anger, then fright, and finally silence. It can take 20 years to play out, exhausting caregivers, family, and friends. As the population ages, we can expect a precipitous rise in the number of Alzheimer's patients. But a new study provides hope that we may be able to mitigate it with diet.
How Alzheimer's takes over the mind is still hotly debated, but we know one thing: There is a gene that increases your odds of getting the disease. It is called APOE4, and it creates a subtly defective version of a protein that normally helps chaperone fats around the body. One of the organs that uses a lot of fat is the brain, where it plays a major role in membrane structure and providing energy. But just how APOE4 might contribute to Alzheimer's is still murky.
New Study
So, a new study from the University of Nevada is an eye-opener. Jingchun Chen and colleagues found a connection between gut microbes, Alzheimer’s, and the APOE4 gene. They identified 10 gut microbial genera associated with Alzheimer’s, with six showing a protective association and four showing a risk association.
The protective bacteria included Eubacterium nodatum, Eisenbergiella, Eubacterium fissicatena, Actinobacterium adlercreutzia, Actinobacterium gordonibacter, and Prevotella. The risk-associated bacteria included Collinsella, Lachnospira, Bacteroides, and Veillonella.
Veillonella has been associated with oral infections in Alzheimer’s patients. Porphyromonas gingivalis is another oral microbe associated with Alzheimer's, and highlights the role of oral bacteria, not just gut bacteria, in dementia.
The association between these microbes and Alzheimer’s was independent of age and sex. Further analysis revealed a correlation between the APOE4 gene and four of the bacteria. One of those was Collinsella. Collinsella has been previously associated with atherosclerosis, rheumatoid arthritis, and type-2 diabetes. Studies have shown that Collinsella exhibits pro-inflammatory effects and affects lipid metabolism, which suggests a functional relationship to APOE4.
Additionally, three bacteria were found to have a protective association with APOE4. These bacteria are involved in the production of butyrate, which has anti-inflammatory properties and helps maintain gut integrity. Butyrate also affects the brain directly, improving its ability to adapt to challenges and to regenerate brain tissue.
We have known for several years now that gut microbes have an important impact on the brain. They can produce both nasty toxins and healthy short-chain fatty acids like butyrate. A diverse and well-balanced community of microbes can keep your gut lining pink and happy, welcoming nutrients while expelling pathogens. But the researchers found that a reduction in microbial diversity was associated with the development of Alzheimer's. Other studies have shown that a healthy gut is typically the most diverse gut.
When certain species of bacteria are wiped out, say by antibiotics, pathogens, or a bad diet, other bully species can take over. That can cause the gut lining to weaken, potentially allowing microbes or toxins to enter the bloodstream. Over time, that can lead to systemic inflammation, which can affect every organ in the body, including the brain. So, on the face of it, it doesn’t sound crazy that bacterial imbalances could lead to Alzheimer’s.
The study could only show associations, so it is possible that the causality goes the other way: Instead of imbalanced microbes leading to Alzheimer’s, perhaps Alzheimer’s causes certain gut bacteria to dominate. The researchers, however, speculate that some of these bacteria may be promising therapeutic targets against Alzheimer's and aging in general.
Due to the incredible complexity of biological systems, it is often difficult to establish causality. However, we know from several mouse studies that microbes can affect brain health. If microbes are causal, that is hugely important, because the makeup of your gut microbes—your microbiota—is under your control.
Every meal you consume changes your microbiota, with some species boosted and others diminished to accommodate the nutrients in your diet. By eating the right foods, you can simultaneously improve diversity and diminish pathogens. That means it is possible that we can control the onset and progression of Alzheimer's with diet and supplements.
What to Do
What kind of diet do you need to lower your odds of getting Alzheimer's? The study shows that a diversity of species is the best indicator of brain health. To improve your gut diversity, you should eat a highly varied diet. One such diet is the Mediterranean diet, which is known for its variety and emphasis on vegetables and fish.
Some dietitians recommend eating 30 different veggies each week. Many of us aren’t even aware that there even are 30 different veggies, but they can be delicious if prepared properly, and, in the Internet age, we have no excuse for not giving them a try. Concentrate on those that are high in fiber, including artichokes, onions, lentils, asparagus, and mushrooms. The fiber feeds the microbes that produce butyrate, keeping your gut and mind in the pink.
If you don’t have the time to cook, you might try a prebiotic supplement that offers a blend of natural fiber and polyphenols that can fill in the gaps. Also, fermented foods are amazing sources of probiotics, prebiotics, and postbiotics (the substances produced by beneficial microbes). These include yogurt (without added sugar), kimchi, kefir, sauerkraut, and natural pickles. The stuff in the center of the store generally do not contain live cultures. The ferments you want are in the refrigerator aisle.
Although the mechanisms are not thoroughly worked out, eating right and maintaining a diverse microbiota can’t hurt, and may prevent or postpone Alzheimer’s. A Lancet Commission on dementia considers that modifiable risk factors contribute to 40 percent of dementia risk. That’s just one more reason to take care of your oral and gut microbes.
References
Cammann, D., Lu, Y., Cummings, M.J. et al. Genetic correlations between Alzheimer’s disease and gut microbiome genera. Sci Rep 13, 5258 (2023).
