【Doctor commentary】The role of gut microbiota in dementia

Alzheimer’s disease is caused by the degeneration of nerve cells, and its progression is very slow. Changes are believed to occur more than 30 years before the onset of symptoms. In the early stages, aggregation of amyloid-beta and phosphorylation of tau lead to neurofibrillary changes. Subsequently, activation of microglia, immune cells in the brain, and chronic inflammation result in neuronal damage and brain atrophy. Since a definitive treatment has not yet been established, prevention is emphasized. The gut-brain connection is thought to be relevant to dementia prevention.

The brain and the gut are closely interconnected through the vagus nerve, emphasizing the importance of the “gut-brain axis.” Administering a strain of lactobacillus called Lactobacillus rhamnosus to model mice has been shown to improve social behavior through the vagus nerve pathway. Metabolites produced by gut bacteria are also implicated in brain function, and characteristics of the gut microbiota have been linked to brain dysfunction.

Building on this knowledge, there is potential that the Bifidobacterium longum strain A1 could prevent the onset of Alzheimer’s disease. When this strain is orally administered to mice with amyloid-beta injected into their brain ventricles, cognitive function improves.

Notably, gene expression analysis in the hippocampus revealed that the administration of Bifidobacterium longum strain A1 suppressed the upregulation of inflammation-related genes. Therefore, it’s conceivable that this strain could mitigate amyloid-beta-induced cognitive impairment.

Furthermore, a randomized, placebo-controlled, double-blind parallel-group trial was conducted with elderly individuals suspected of having mild cognitive impairment (MCI) as subjects. The results confirmed that the intake of Bifidobacterium longum strain A1 improved cognitive function in those diagnosed with MCI.

Currently, various mechanisms are being considered for the action of Bifidobacterium longum strain A1 on the central nervous system, including effects via soluble factors, influence on peripheral macrophages through the blood-brain barrier, and actions through the vagus nerve.

It’s believed that these mechanisms, either individually or in combination, contribute to the cognitive improvement effects of Bifidobacterium longum strain A1.

With aging, the gut microbiota changes, especially in individuals over 60, where Bifidobacterium tends to decrease while bacteria like Escherichia coli increase, leading to “aging of the gut microbiota.”

This phenomenon is known to have causal relationships with various age-related conditions. Leaky Gut, in particular, is a significant factor in many age-related diseases, including implications for cognitive impairment.

Regular intake of probiotics or prebiotic materials that promote Bifidobacterium growth is considered to help maintain a healthy gut microbiota and intestinal barrier function, making it an effective anti-aging strategy.

Dr. Munenori Matsuzawa, Chief Medical Officer, Aoyama Medical Clinic.

References：

1) Wu L. Zheng R. Zinellu A. et al A Cross Sectional Study of Compositional and Functional Profiles of Gut Microbiota in Sardinian Centenarians. mSystems.2019:4: e-00325-19

2) Yang H. Liu A. Zhang M, et al. Oral Administration of Live Bifidobacterium Substrains Isolated from Centenarians Enhances Intestinal Function in Mice.