Oral quercetin nanoparticles in hydrogel microspheres alleviate high-altitude sleep disturbance based on the gut-brain axis

High-altitude sleep disturbance is a common symptom of acute mountain sickness, which can be alleviated via modulation of the gut-brain axis. Quercetin (Que) is used to modulate gut microbiota and serves as a potential drug to regulate the gut-brain axis, but the poor solubility and bioavailability affect its biological functions. Here, Que nanoparticles (QNPs) were prepared with zein using an antisolvent method, and QNP-loaded calcium alginate hydrogel microspheres (QNP@HMs) were prepared using electrospinning technology to improve the gastrointestinal stability and intestinal adhesion of QNPs. In the mouse model of high-altitude sleep disturbance, oral QNP@HM before high altitude prolonged sleep duration, improved blood cell recovery, spontaneous behavior and short-term memory, and reduced such inflammation factors as TNF-α and iNOS of mice. Moreover, QNP@HM enhanced the abundance of probiotics, especially in Lactobacillus and Lachnospira, and reduced intestinal inflammation. However, in the mice with gut sterilization by long-term oral antibiotics, QNP@HM showed no therapeutic effect. QNP@HM is possibly a promising medication for the prevention of high-altitude sleep disturbance based on the gut-brain axis.