Long‐Term Krill Oil Administration Alleviated Early Mild Cognitive Impairment in APP/PS1 Mice

Scope Alzheimer's disease is an age‐dependent neurodegenerative disorder. Mounting studies focus on the improvement of advanced cognitive impairment by dietary nutrients. Krill oil (KO), a rich source of DHA/EPA and astaxanthin, is effective in improving cognitive function. The study mainly investigates the protective effects of long‐term KO administration on early cognitive impairment. Methods and results Results show that 2 months KO administration (50 and 100 mg kg −1 BW) can dramatically promote learning and memory abilities. Mechanism studies demonstrate that KO reduces amyloid β concentration by regulating the amyloidogenic pathway, inhibits neuro‐inflammation via regulating TLR4‐NLRP3 signaling pathway, and prevents neuron injure. KO supplementation also enhances gut barrier integrity, reduces serum lipopolysaccharide leakage, and alters the gut microbiota by reducing Helicobacteraceae , Lactobacillaceae proportion, increasing Dubosiella and Akkermansia relative abundance. Particularly, a significant increase of isovaleric acid, propionic acid, and acetic acid levels is observed after KO supplementation. Correlation analysis shows that short‐chain fatty acids (SCFAs), gut microbiota, and cognitive function are strongly correlated. Conclusions The results reveal that KO relieves early mild cognitive impairment possibly for its role in mediating the gut microbiome‐SCFAs‐brain axis. Thus, KO may provide potential intervention strategies to prevent cognitive impairment in the early stages through the microbiota‐gut‐brain axis.