Intratracheal Lactobacillus rhamnosus attenuates poultry-house PM2.5-induced lung inflammation in broilers by remodeling the pulmonary microbiota-metabolite axis.

Fine particulate matter (PM2.5) in intensive farming systems is a bioaerosol mixture that poses severe risks to respiratory health; however, the role of the lung microbiome in PM2.5-induced toxicity and its potential as a therapeutic target remain poorly understood. Here, we investigated the pulmonary toxicity of poultry-house PM2.5 and evaluated the protective efficacy of intratracheal Lactobacillus rhamnosus (L. rhamnosus) administration in a broiler model. Exposure to PM2.5 caused significant lung pathological injury, oxidative stress, and inflammatory responses. Integrative analysis of 16S rRNA gene sequencing and untargeted metabolomics revealed that PM2.5 disrupted the pulmonary microecology, depleting commensal Lactobacillus while enriching opportunistic pathogens (Escherichia-Shigella), which coincided with a marked suppression of tryptophan metabolism. Strikingly, L. rhamnosus intervention reversed this dysbiosis and specifically restored the levels of indole derivatives, particularly indole-3-lactic acid (ILA). Correlation analysis further demonstrated that elevated ILA levels were strongly associated with reduced pro-inflammatory cytokines and improved antioxidant capacity, suggesting a strong correlation between L. rhamnosus administration, the reinstatement of microbiota-derived tryptophan metabolites, and respiratory protection. Collectively, our findings provide the evidence that identifying and restoring key microbial metabolites offers a potent remediation strategy against environmental bioaerosol-induced respiratory injury.