Sweet potato polysaccharides ameliorate colitis via activation of PINK1/PARK-mediated mitophagy and modulating gut microbiota

The pathogenesis of UC involves multifaceted disruptions, including immune dysregulation, gut microbiota dysbiosis, and mitochondrial homeostasis imbalance, underscoring the urgent need for effective therapeutic interventions. While polysaccharides have garnered attention for their potential in modulating intestinal inflammation, their underlying molecular mechanisms remain underexplored. Herein, we isolated a high-molecular-weight heteropolysaccharide (SPP) from sweet potato, with a molecular weight of 918.12 kD, featuring a pyranose ring backbone, mixed α- and β-glycosidic linkages, and a flaky microscopic morphology. In a dextran sulfate sodium (DSS)-induced acute colitis mouse model, oral administration of SPP markedly alleviated clinical symptoms, reduced the disease activity index, attenuated histopathological damage, and restored mucin barrier integrity. Cytokine profiling revealed that SPP suppressed the secretion of pro-inflammatory mediators (IL-6, IL-1β, TNF-α) while elevating anti-inflammatory IL-10 levels. Mechanistically, SPP upregulated expression of mitophagy-related proteins (PINK1, PRKN, PHB2, LAMP2, Beclin-1), increased the LC3-II/LC3-I ratio, and diminished P62 and TOMM20 accumulation, indicating activation of the PINK1/PRKN-dependent mitophagy pathway to enhance mitochondrial quality control. Moreover, SPP downregulated core components of the NLRP3 inflammasome (NLRP3, ASC, Caspase-1) and restored tight junction proteins (ZO-1, Claudin-1, Occludin), thereby reinforcing intestinal epithelial barrier function. High-throughput 16S rRNA sequencing of the gut microbiota demonstrated that SPP reduced abundances of pathogenic taxa such as Escherichia-Shigella and Bilophila, while enriching beneficial and butyrate-producing genera including Akkermansia, Turicibacter, and Romboutsia. These findings elucidate SPP’s therapeutic efficacy against colitis through synergistic mechanisms involving microbiota remodeling, PINK1/PRKN-mediated mitophagy activation, NLRP3 inflammasome suppression, and epithelial barrier reconstruction, supporting SPP as a candidate functional dietary component for inflammatory bowel disease.