Researchers have found that bile acid metabolism plays a significant role in age-related neurodegeneration and cognitive decline. As individuals age, bile acids produced by the gut microbiome accumulate and can harm the brain. By sequestering bile acids in the intestine with specific molecules, researchers have shown a reduction in their contribution to brain aging in animal models. There is potential for adjusting the gut microbiome balance through fecal microbiota transplant from a younger individual to produce similar benefits, although this approach requires further investigation.
Recent studies have indicated a connection between changes in bile acids and age-related cognitive impairment. Lower levels of unconjugated primary bile acids and increased levels of certain metabolites are closely linked to cognitive decline severity in diseases like Alzheimer’s and Parkinson’s. Age-related alterations in the gut microbiota impact the levels of circulating bile acids, influencing brain health. Specific secondary bile acid metabolites derived from bacteria show a correlation with cognitive decline symptoms.
Elevated levels of serum conjugated primary bile acids and ammonia in the elderly, individuals with cognitive impairment, and aging rodents are associated with changes in hippocampal synapses and cognitive decline, particularly in females. Experiments demonstrate how bile acids and ammonia can induce synaptic loss and cognitive impairment, while manipulating intestinal bile acid transport affects brain bile acid levels and cognitive function. Treatment with an intestinal bile acid sequestrant has shown promise in alleviating cognitive impairment in aging mice.
Link: https://doi.org/10.1016/j.xcrm.2024.101543
