Calorie-restricted diets can improve Alzheimer’s disease (AD) outcomes in mouse models by reducing certain gut microbiome bacterial species. However, the clinical application of caloric restriction as a disease treatment is unlikely because it can leave elderly individuals malnourished. The Cox team is exploring other approaches to modify the gut microbiome, including dietary changes and testing whether introducing specific, beneficial bacteria might improve cognitive outcomes.
During the first Microbiome Consortium funding cycle, Dr. Cox’s team focused on the effects of Mediterranean and Western diets on amyloid mouse models. They found that a Western diet altered the gut microbiome and increased amyloid plaque burden in males. While the Mediterranean diet increased beneficial microbes, it did not reduce amyloid levels, suggesting that additional microbiome or dietary intervention is needed. Based on previous work on dietary interventions, Dr. Cox’s lab also found that a specific strain of bacteria (Akkermansia) reduced amyloid levels in female mice, which was linked to a reduction in key peripheral immune cells and a shift in mouse metabolism.
As the next funding cycle begins, Dr. Cox’s team will test the hypothesis that certain diets affect how AD develops by altering how the gut microbiota interact with the body’s immune system and metabolism. All members of the Microbiome consortium are shifting their focus to the metabolic consequences of changes in the gut microbiome as they work to identify specific mechanisms as potential therapeutic targets. Dr. Cox’s lab will focus on the effects of a high-fat Western diet and how two bacterial species, Akkermansia and Bacteroides, influence those effects. Akkermansia (designated BWH-H3) is associated with reduced amyloid pathology in mice, whereas Bacteroides is associated with worsening amyloid pathology. This project has three goals: 1) investigate the degree to which these two bacteria influence amyloid pathology and cognitive function in mice fed a Western diet, 2) identify the metabolic pathways influenced by these bacteria, and 3) investigate the immune cell populations and pathways influenced by each bacterial strain.
