Bilberry extract ameliorates high-AGEs diet induced AD-like pathological changes through the modulation of gut microbiota

Background: Previous research had suggested a potential link between advanced glycation end products (AGEs) and Alzheimer's disease (AD) pathology, but conclusive evidence was lacking. It remained unclear whether anthocyanins, known for their anti-inflammatory and antioxidant properties, could counteract the harmful effects of AGEs. Purpose: The purpose of this study was to explore whether high-AGEs could lead to AD-like pathology changes and whether bilberry (Vaccinium myrtillus L.) extract (BE) could mitigate the impact of AGEs. Methods/study design: In this study, wild-type naturally aging Sprague-Dawley (SD) rats were fed high-AGEs diet. Additionally, BE was used as an intervention to assess its potential in mitigating the impact of AGEs. The entire feeding process lasted 15 months, with feces, blood, and urine samples collected every three months. After 15 months of feeding, conducted the Morris Water Maze and open field tests, then anesthetized the rats and collect cerebrospinal fluid, colon, blood, and brain. Results: AGEs induced typical AD-like pathological changes including cognitive impairment, Aβ aggregation, Tau hyperphosphorylation, neuron loss and neuroinflammation. The high-AGEs diet also caused intestinal inflammation, disrupted the intestinal barrier, and led to gut microbiota dysbiosis, along with a reduction in short-chain fatty acids (SCFAs). BE intervention successfully alleviated these pathological changes, repaired intestinal damage, regulated gut microbiota, and increased SCFAs levels. Conclusion: BE showed promise in mitigating AGEs-related effects, highlighting its potential as a therapeutic agent against AGEs-related AD pathology.