Gut Microbiota and Alzheimer's Disease: Genetic Association Study

The following is a summary of a 2023 study along with several newer studies on the gut microbiome and Alzheimer's

Research has shown that an imbalance in the gut microbiota is linked to Alzheimer's disease through neuroinflammation across the microbiota-gut-brain axis. Observational studies have also found that Alzheimer's patients have less diverse gut microbiomes, which could contribute to the disease.

In this study, the researchers used a large genome-wide association study to analyze the genetic correlation between 119 gut microbiota genera and Alzheimer's disease.

They found that 10 genera had a significant correlation with Alzheimer's disease, with three of them (Eubacterium fissicatena, Collinsella, and Veillonella) being independently significant. The study also found that proinflammatory gut microbiota, such as Collinsella, might promote Alzheimer's disease development through interaction with the APOE genotype.

These findings suggest that the gut microbiota could serve as biomarkers and targets for Alzheimer's disease treatment and intervention. Further research is needed to understand the causal relationships between the gut microbiota and Alzheimer's disease.
"Genetic correlations between Alzheimer’s disease and gut microbiome genera"

That’s cool… But what can we do about this?

A new mouse study points to glutamine metabolism via the gut microbiome as a pathway that may help to modify the course of Alzheimer’s disease. In the study, Bifidobacterium breve along with environmental enrichment “alleviated amyloid-β (Aβ)-induced cognitive impairment and enhanced synaptic function in Alzheimer’s disease (AD) mice.” The researchers found that the alterations to glutamine metabolism by the gut microbiome were likely the important pathway. [ref]

Bifidobacterium breve is available in many Bifidobacteria probiotics and even as a stand-alone powder (which I haven’t used - yet).

A mouse model of Alzheimer’s also showed that magnesium l-threonate delayed Alzheimer’s symptoms by altering the gut microbiome and decreasing inflammation in the gut. One of the altered gut microbes was an increase in Bifidobacteria with magnesium l-threonate.[ref]

Magnesium l-threonate is readily available online.

What about in humans? The research is not quite as clear — other than the fact that the gut microbiome is likely involved in Alzheimer’s.

A new study using Mendelian randomization shows that Holdemanella (negative) and Parabacteroides (positive) bacteria are likely playing a causal role in the onset of Alzheimer’s. These bacteria are linked to reduced glutamine and increased alanine levels.[ref] Some studies point to increasing Parabacteroides with resistant dextrin or soluble fiber.[ref][ref] While prebiotic powders are available online, you may be better off with healthy dietary changes that include fiber (if you don’t regularly get enough fiber.) Cordyceps mushrooms and other mushrooms that contain H1 polysaccharides may also promote the abundance of Parabaceroides.[ref]

A crossover trial looked at the differences in amino acids and metabolites based on either a modified Mediterranean Keto Diet or the DASH diet (AHA diet). The study was small, but they found that the heart association diet had no effect, but the modified Mediterranean keto diet caused interesting changes in the gut microbiome and improved memory. Glutamine and valine were the two metabolites that decreased due to diet.[ref]

Another new study looked at urine metabolites, genetics, and the microbiome in people with Alzheimer’s and with a matched cohort. They found a decrease in formate and fumarate concentrations in Alzheimer’s patients that they then found correlated to decreased formate production by the gut microbiome. “Formate is a fermentation production of anaerobic bacteria in the gut and the gut microbiome metabolism can account for up to 50% of the overall formate production in the host”.

Microbial tryptophan degradation is one source of formate, and decreased tryptophan increases cognitive deficits in Alzheimer’s. The study goes on to identify genetic variants in the Alzheimer’s patients that were also associated with the formate pathway.[ref]

Animal studies show that a high tryptophan diet helps to reduce neuroinflammation in a mouse model of Alzheimer’s.[ref] Foods high in tryptophan include meat, shellfish, dairy, fish, egg yolks, pineapple, pumpkin seeds, and bananas.

My takeaways:

While there’s still a lot to learn, it seems that researchers are pinpointing several important pathways affected by the gut microbiome that likely play a causal role in Alzheimer’s.