Barley polysaccharides modulate metabolic and mild cognitive impairment in naturally aging mice through the liver−gut−brain axis

Cognitive impairment associated with natural aging significantly reduces the healthy lifespan of elderly adults. Barley is rich in polysaccharides, particularly starch and dietary fibers such as β-glucan and xylan. As the predominant components of barley water extracts, these polysaccharides, especially dietary fibers, exhibit substantial potential in promoting gut and brain health. In this study, we established a natural aging model by exposing mice to a high-fat diet and chronic stress for 220 consecutive days. Our findings revealed   that barley polysaccharides   ameliorated cognitive deficits, particularly long-term memory, by modulating neurotransmitter levels and reducing corticosterone. Barley polysaccharides also alleviated lipid metabolism disorders, reduced liver lesions, and decreased body weight as well as the percentage of visceral fat in mice by regulating bile acid and l -lysine metabolism. Additionally, barley polysaccharides enhanced intestinal barrier integrity and reshaped the gut microbiota. They significantly increased the abundance of norank_f_Muribaculaceae and unclassified f_Lachnospiraceae , leading to elevated short-chain fatty acid levels, especially butyric acid, which contributed to improved cognitive function. These findings suggest that barley polysaccharides could serve as a promising dietary intervention to mitigate cognitive decline associated with natural aging through the liver-gut-brain axis.