WIPButyrate produced by the Lycium ruthenicum polysaccharide alleviated sleep deprivation-induced chronic fatigue syndrome in mice through promoting microglial autophagy.

This study explored whether Lycium ruthenicum polysaccharide (LRP) influences gut microbiota-derived short-chain fatty acids (SCFAs) and neuroinflammatory responses in a sleep deprivation-induced CFS-like mouse model. Oral LRP was associated with improved fatigue-related behavioral performance, reduced neuronal injury, and better cognitive and motor outcomes. These changes coincided with an increased abundance of putative butyrate-producing bacteria and higher butyrate levels in serum and brain. To examine a possible downstream link, sodium butyrate was tested in cultured microglia and attenuated inflammatory activation while improving mitochondrial stress and autophagy-related readouts. Overall, the data suggest that microbiota-associated butyrate changes may contribute to the observed benefits of LRP, supporting its potential as a food-derived strategy for fatigue-related neuroinflammation.