Polygonatum cyrtonema Polysaccharides Alleviate Sleep Deprivation-Induced Behavioral Disorders via Gut Microbiota-Dependent Regulation of the Butyrate-HDAC3 Signaling Axis

This study aimed to determine whether Polygonatum cyrtonema polysaccharides (PCP) protect against sleep deprivation (SD)-induced neurobehavioral disorders via gut microbiota and epigenetic regulation. PCP was characterized as a structurally stable, glucose-rich heteropolysaccharide. Intervention with PCP significantly alleviated anxiety- and despair-like behaviors, yielding a 42.7% improvement in open-arm exploration time during the EPM test compared to the SD group. Mechanistically, PCP preserved intestinal and blood-brain barrier integrity, suppressed microglial activation, and repaired hippocampal synapses. Microbial profiling revealed that PCP reshaped the gut microbiota by enriching butyrate-producing taxa, leading to a 1.3-fold elevation in fecal butyrate levels. This metabolic shift suppressed hippocampal HDAC3 activity and drove a 60.8% increase in BDNF expression. Notably, these neuroprotective effects were completely abolished in microbiota-depleted mice. Overall, PCP relies on a microbiota-driven cascade of butyrate production and subsequent epigenetic regulation to maintain gut-brain homeostasis.