Respiratory Exposure to Agriculture Dust Extract Alters Gut Commensal Species and Key Metabolites in Mice

Exposure to agricultural dust containing antimicrobial-resistant pathogens poses significant health risks for workers in animal agriculture production. Beyond causing severe airway inflammation, pollutants are linked to intestinal diseases. Swine farm dust is rich in ultrafine particles, gram-positive and gram-negative bacteria, and bacterial components such as lipopolysaccharides (LPS; endotoxins). In our previous study, we demonstrated that intranasal exposure of male and female C57BL/6J mice to 12.5% hog dust extract (HDE, containing 22.1-91.1 EU/mL) for 3 weeks resulted in elevated total cell and neutrophil counts in bronchoalveolar lavage fluid and increased intestinal permeability compared to saline controls. Now, we report that 16S and metagenomic analyses of Week 3 stool samples from HDE-treated mice indicate a reduced abundance of the beneficial species Akkermansia muciniphila and Clostridium sp. ASF356 and Lachnospiraceae bacterium. Bacterial alpha diversity showed increased species evenness in fecal samples from HDE-treated mice (Pielou's evenness, p = 0.047, n = 5-6/group). Metabolomic analysis also indicated significant reductions in key metabolites involved in energy metabolism, including riboflavin (p = 0.027, n = 11) and nicotinic acid (p = 0.049, n = 11), as well as essential amino acids, such as inosine (p = 0.043, n = 11) and leucine (p = 0.018, n = 11). While HDE exposure does not robustly alter overall microbial abundance or community structure, it leads to specific reductions in beneficial bacterial species and critical metabolites necessary for maintaining intestinal homeostasis by supporting energy metabolism, gut barrier function, microbiota balance, and immune regulation. The results of this study underscore the potential risks for gut health posed by inhalation of agricultural dust.