Oligosaccharides from Polygonatum cyrtonema Hua ameliorate colitis-induced lung injury via modulation of the gut-lung axis through NF-κB and Nrf2 pathways

BACKGROUND: The gut-lung axis is a bidirectional communication network linking intestinal and pulmonary homeostasis through shared immunological and molecular mechanisms, conceptually consistent with the traditional Chinese medicine theory of "lung-intestine combined treatment." Polygonatum cyrtonema Hua is an edible medicinal plant with reported anti-inflammatory and antioxidant properties, yet its role in intestinal inflammation-associated lung injury remains unclear. MATERIALS AND METHODS: Dextran sulfate sodium (DSS)-induced colitis and lipopolysaccharide (LPS)-induced lung injury models were established in vivo, while LPS-stimulated A549 lung epithelial cells were used in vitro. The protective effects of Polygonatum cyrtonema oligosaccharides (PFOS) were evaluated, with particular focus on NF-κB and Nrf2 signaling pathways. The Nrf2 inhibitor ML385 was applied in vitro to verify pathway involvement. Non-targeted fecal metabolomics was conducted to assess PFOS-mediated metabolic modulation. RESULTS: PFOS significantly alleviated DSS-associated lung histopathological damage, reduced inflammatory cell infiltration, and improved epithelial barrier integrity. PFOS suppressed pulmonary proinflammatory cytokines, including TNF-α and IL-6, decreased myeloperoxidase activity, and attenuated oxidative stress by lowering malondialdehyde levels while enhancing antioxidant enzymes such as superoxide dismutase and HO-1. Mechanistically, PFOS inhibited NF-κB activation and promoted Nrf2/HO-1 signaling in lung tissues and LPS-stimulated A549 cells, effects that were partially reversed by ML385. Metabolomics analysis revealed that PFOS corrected DSS-induced disturbances in amino acid and lipid metabolism, with enrichment in cAMP, PPAR, and tryptophan-related pathways. CONCLUSIONS: PFOS protects against colitis-associated lung injury by modulating the gut-lung axis through coordinated anti-inflammatory and antioxidant mechanisms involving NF-κB inhibition and Nrf2 activation, supporting its potential therapeutic application in gut-lung axis-related diseases.