Bioactive polysaccharides from the industrial crop Platycodon grandiflorus restore intestinal barrier integrity and suppress bEVs-mediated pyroptosis: A functional component for respiratory health management

Abstract

Platycodon grandiflorus is widely recognized as an industrial crop due to the high value of its bioactive polysaccharides (PGP). Despite its traditional use for pulmonary and gastrointestinal health, the underlying mechanisms remain poorly defined. This study investigated whether PGP intervention alleviates cigarette smoke (CS)-induced COPD in mice by restoring intestinal barrier integrity and reducing the translocation of lipopolysaccharide-carrying bacterial extracellular vesicles (LPS-bEVs) to the lung. Our results showed that a 7-week intervention with PGP significantly ameliorated CS-induced COPD symptoms, with the high-dose group exhibiting the most pronounced effects. PGP supplementation effectively mitigated body weight loss, pulmonary damage, intestinal shortening, and inflammatory cell infiltration. Notably, COPD-induced chronic mild hypoxia led to intestinal tissue hypoxia, which was alleviated by PGP through suppression of pathological glycolysis. This, in turn, restored the balance of cellular renewal and differentiation, improved intestinal barrier integrity, and limited the translocation of gut microbiota and their metabolites. In the lungs, PGP inhibited the activation of the non-canonical inflammasome pathway (Caspase11/GSDMD) triggered by LPS-bEVs, thereby attenuating pulmonary inflammation and preventing further injury. These findings establish PGP as a bioactive industrial crop component that regulates the gut-lung axis via dual mechanisms involving intestinal barrier protection and pulmonary pyroptosis suppression. This work provides a mechanistic foundation for developing PGP-based functional ingredients for respiratory health management, highlighting the value of P. grandiflorus beyond traditional applications toward evidence-based industrial product development.