Polygonati Rhizoma polysaccharide suppresses microglial activation and promotes functional recovery of spinal cord via improving intestinal microbiota.

Spinal cord injury (SCI) can disrupt the gut microbiome and metabolites, impacting prognosis, substantially impairing quality of life, and leading to high socioeconomic costs (Jing et al., 2021). Recent studies indicate that plant polysaccharides exhibit antimicrobial, anti-inflammatory, and immune-enhancing properties, contributing positively to various neurological disorders; however, their role in SCI remains uncertain (Hou et al., 2020 [2]; Aswini et al., 2021 [3]; Dou et al., 2019 [4]). Polygonati Rhizoma polysaccharide (PRP) has shown anti-inflammatory and immunoregulatory effects, but its role in SCI remains unexplored. This study investigated whether PRP facilitates functional recovery after SCI by modulating the gut microbiota and SCFA levels. PRP was administered to SCI mice, and motor function was assessed using DeepLabCut-based behavioral analysis. Histological evaluations were performed with H&E, Nissl, and immunofluorescence staining. Microglial activation and inflammation were analyzed by Western blot and immunofluorescence. Gut microbiota composition and SCFAs were examined through 16S rRNA sequencing and targeted metabolite profiling. PRP treatment significantly improved motor function, reduced microglial activation, and attenuated neuroinflammation. These effects were associated with restoration of microbial diversity and elevated butyrate levels. This study highlights the role of the gut-brain axis in neural regeneration and suggests PRP as a promising therapeutic candidate for SCI.