Abstract

Gut microbiota and their metabolites may shape pulmonary immune responses and infection progression. Plant-derived polysaccharides, such as Atractylodes lancea polysaccharides, have shown prebiotic activity, yet their protective mechanisms in pneumonia remain unclear. Here, A. lancea polysaccharides (ALPs), a water-soluble acidic fraction mainly composed of arabinose, galacturonic acid, glucose, and galactose with a predominant molecular weight of 3.52 kDa, were evaluated in a murine model of Staphylococcus aureus-induced lung injury. Oral pretreatment with ALP (100 or 400 mg/kg) alleviated lung injury, improved intestinal barrier integrity, reshaped the gut microbiota by enriching Limosilactobacillus, restored tryptophan-related metabolites, increased AhR expression in the lung and colon, and reduced inflammatory responses. Broad-spectrum antibiotic treatment markedly blunted the effects. Collectively, ALP protected against S. aureus-induced lung injury in association with gut microbiota remodeling, improved barrier integrity, and restored tryptophan metabolism along the gut-lung axis.