Lung microbiota-mediated biotransformation of mogroside preserves pulmonary barrier integrity and attenuates PM2.5-induced inflammation via NF-κB–Th17 modulations

Abstract PM 2.5 -induced lung injury challenges poultry health with limited treatments. Mogroside’s unique therapeutic impact on pulmonary inflammation may involve modulating the lung microbiome, which influences immune function and respiratory health. We first demonstrated that mogroside (MG) supplementation improved growth performance and mitigated PM 2.5 -induced alveolar damage, inflammatory cytokine release, and Th17 differentiation ( p < 0.05). MG increased the abundance of beneficial bacteria, particularly Lactobacillus ( p < 0.01). Notably, MG IIE accumulated in lung tissues and bronchoalveolar lavage fluid (BALF). To further clarify the role of microbe–metabolite interactions, BALF from MG-treated broilers was transplanted. Only complete BALF containing both MG and microbiota significantly alleviated fibrosis ( p < 0.05), reshaped lung microbial composition, and modulated metabolites such as taurine and lactic acid. Microbiome analysis identified Sphingomonas as a key taxon enriched in MG-BALF, strongly correlated with protective metabolites. In vitro assays confirmed that Sphingomonas degraded MG IIE into mogrol via β-glucosidase activity. Finally, a Calu-3–Jurkat T lymphocytes co-culture model revealed that MG IIE, particularly in combination with Sphingomonas metabolites, preserved barrier integrity, suppressed NF-κB phosphorylation, reduced ROS, and inhibited Th17-associated cytokine expression. Collectively, MG IIE and its Sphingomonas -mediated metabolites form a lung microbiota–metabolite–host axis that protects against PM 2.5 -induced pulmonary injury.