Ophiopogon japonicus polysaccharide ameliorates pulmonary fibrosis via gut microbiota-metabolite crosstalk.

Abstract

Despite the clinical application of Ophiopogon japonicus in idiopathic pulmonary fibrosis (PF), its key anti-fibrotic components and underlying mechanisms remain poorly defined. Using a bleomycin-induced murine PF model, we systematically compared the efficacy of the total extract (OJTE), polysaccharides (OJTP), saponins (OJTS), and flavonoids (OJTF). The active component was further investigated via integrated metagenomics and metabolomics (serum/feces) to decipher the gut-lung axis mechanism. All O. japonicus components attenuated lung injury and collagen deposition, with OJTP demonstrating the most potent efficacy (reducing lung hydroxyproline content by 42.12% (p&#x202f;<&#x202f;0.01) compared to the model group). Multi-omics analysis revealed that OJTP remodeled the gut microbiota, notably enriching probiotic strains such as Muribaculaceae bacterium (logFC&#x202f;=&#x202f;2.17) and Duncaniella muricolitica (logFC&#x202f;=&#x202f;2.06), as well as the polysaccharide-utilizing species Prevotella sp. MGM2 (logFC&#x202f;=&#x202f;2.79). Concomitantly, OJTP significantly altered host metabolism, upregulating key metabolites including urobilinogen (p&#x202f;<&#x202f;0.0001) and 5-amino valeric acid betaine (5-AVAB, p&#x202f;<&#x202f;0.002). These metabolites are implicated in porphyrin and amino acid metabolism, respectively. Correlation networks further established strong associations between these OJTP-modulated microbes and metabolites. Our study first identifies OJTP as the primary bioactive component of O. japonicus against PF. We propose a novel trans-organ mechanism wherein OJTP ameliorates PF via orchestrating a "gut microbiota-metabolite" axis, highlighting the therapeutic potential of targeting polysaccharide-probiotic synergy.