Neurodegeneration — 7

THE GUT MICROBIOME

We can see the relationship between the gut microbiome and Alzheimer’s disease getting clearer. In a 2023 study from Washington University in St. Louis comparing 49 individuals with preclinical high risk of the disease to 115 participants without such high-risk biomarkers, the gut microbiome offered intriguing insights. Not only did the microbiome ingredients differentiate the two groups, but in examining brain PET scans, reinforcing correlations were found in the Aβ plaques and Tau, along with cerebrospinal fluid p-tau-181 level and the ratio of Aβ42/Aβ40. So, what was causing what?

While that study reinforced a correlation, gut microbiome transplantation from people with Alzheimer’s and aged-matched healthy controls to young healthy rats is even more revealing. In that animal model, as assessed by a team of scientists at University College Cork, Ireland, there was cognitive impairment proportional to the severity of the dementia, and abnormal behavior tied to changes in the hippocampus metabolome. The researchers also found diminished ability to grow new neurons in the lab from the blood of the participants with Alzheimer’s. Multiple other studies in mouse experimental models of Alzheimer’s have confirmed gut microbiome–induced microglial activation, underlying the gut’s role of promoting Aβ plaque and hyperphosphorylated Tau. In particular, the metabolites from the gut microbiome, which include short-chain fatty acids, activate immune cells to produce cytokines that disrupt the blood-brain barrier and induce neuroinflammation. Immune cells from the gut have even been found to migrate to the brain. We must conclude that the gut-brain axis plays a pivotal role in the development of Alzheimer’s disease. That also provides an opportunity to intervene with the rapidly evolving landscape of prebiotics and probiotics in the future, manipulating the gut microbiome’s composition to reduce brain inflammation.