Protective Effects of <i>Auricularia auricula</i> Polysaccharides on Acute Lung Injury by Regulating Intestinal Flora and Metabolism

ABSTRACT Acute lung injury (ALI) is a serious global respiratory disease lacking completely safe drug treatments. This study investigated the protective mechanism of Auricularia auricula polysaccharides (AAP; 100, 200, and 400 mg/kg) against lipopolysaccharide (LPS)‐induced ALI in mice. The results demonstrated AAP's efficacy in attenuating LPS‐induced ALI. AAP intervention significantly reduced pulmonary edema (lung W/D ratio: 3.5–4.0 vs. LPS 5.2) and bronchoalveolar protein leakage (493–567 µg/mL vs. LPS 616 µg/mL) compared to the LPS group. AAP treatment also dose‐dependently suppressed key pro‐inflammatory cytokines (TNF‐α: 56‐142 pg/mL vs. LPS 184 pg/mL; IL‐1β: 42–45 pg/mL vs. LPS 73 pg/mL; IL‐6: 6–15 pg/mL vs. LPS 31 pg/mL) and effectively restored antioxidant capacity (GSH‐Px: 56.0‐56.1 U/mg prot vs. LPS 41.4 U/mg prot; SOD: 212‐233 U/mg prot vs. LPS 186 U/mg prot; MDA: 0.90–0.94 nmol/mg prot vs. LPS 1.54 nmol/mg prot). Critically, different AAP doses selectively stimulated probiotic growth in the gut. Spearman correlation analysis revealed that these AAP‐modulated probiotics were strongly associated with significant alterations in host metabolic profiles. This metabolic remodeling was further linked to improvements in ALI‐related biochemical parameters described above. Our results indicate that pre‐intervention with AAP attenuates ALI primarily by modulating gut flora composition and associated metabolic pathways. This flora‐metabolite interplay ultimately mediates lung protection via the gut–lung axis, enhancing anti‐inflammatory and antioxidant responses. The present study suggests AAP's potential as a dietary protective agent against ALI, providing a novel therapeutic path focused on the gut‐lung axis.