Ganoderma lucidum polysaccharides alleviate cognitive impairment in sleep-deprived mice: Association with gut...

Sleep deprivation (SD) can impair cognitive function through multiple processes, including systemic inflammation, oxidative stress, and synaptic dysfunction, yet effective interventions remain limited. Therefore, this study investigated whether Ganoderma lucidum polysaccharides (GLP) could alleviate SD-induced cognitive impairment and whether such effects were accompanied by changes in gut microbiota, fecal metabolism, and indicators related to the microbiota-gut-brain (MGB) axis. In a chronic SD mouse model, GLP administration not only improved memory performance and anxiety-like behaviors but also increased hippocampal BDNF levels and the expression of the synapse proteins PSD-95 and SYP. Integrated 16S rRNA sequencing and untargeted metabolomics revealed that GLP remodeled the gut microbial landscape, enriching genera such as Kurthia and Roseburia, suppressing Escherichia-Shigella, and shifting fecal metabolic profiles, with elevated gamma-glutamylglycine and reduced cyclic melatonin as representative metabolic signatures. These peripheral changes were accompanied by reduced serum lipopolysaccharide (LPS) and inflammatory cytokines, alongside a more favorable hippocampal profile characterized by enhanced Nrf2-related antioxidant responses, improved AQP4 distribution, and diminished Aβ1-42 deposition. Correlation analyses further linked taxa responsive to GLP, particularly Kurthia and Escherichia-Shigella, to metabolite shifts, behavioral outcomes, and hippocampal markers. Collectively, these findings indicate that the cognitive benefits of GLP in SD mice are closely associated with coordinated changes across the MGB axis, providing a foundation for further exploration of GLP as a functional food candidate.