Cold-ammonia co-exposure leads to gut microbial functional dysregulation by activating lung-gut axis-mediated immune pathways-16s
Background: Cold and ammonia co-exposure, as common environmental stressors, induces exacerbated pulmonary dysfunction in people and animals. Notably, emerging evidence suggests that such pulmonary dysfunction initiates gut microbiota dysbiosis and systemic immune hyperactivation via lung-gut axis. Yet the molecular crosstalk underlying this interorgan regulation and its functional impacts on microbial metabolism remain poorly defined.Results: Our study integrated multi-omics approaches to elucidate the mechanisms by which cold and ammonia environments, both alone or in coupling, affect the lung-gut axis function in growing pigs. 16S rRNA sequencing of bronchoalveolar lavage fluid revealed that the cold and ammonia environments synergistically increased the relative abundance of potential pathogenic bacteria, such as Actinobacteria and Brevundimonas. Further metabolomic and transcriptomic analyses of lung and pulmonary lymph nodes demonstrated that the cold and ammonia environments synergistically upregulated lysophospholipid metabolites and enriched the cAMP/cGMP-PKG signaling pathways. These findings suggest that immune cell migration signals are mediated via GPCR receptors, driving the recruitment of gut-derived immune cells to the lungs. The cross-organ redistribution of immune resources resulted in impaired intestinal barrier function and significant alterations in the gut microbiota composition. Functional annotation further revealed that the cold and ammonia environments synergistically suppressed lipid and amino acid biosynthesis pathways in gut microbiota, while lysosomal function and biofilm formation pathways were concurrently activated. In addition, dysregulation of the Segatella/Leyella ratio in the gut may signify dysfunction of gut microbial metabolism.Conclusions: Our findings suggest that multiple environmental factors exert synergistic effects on lung-gut immune interactions and gut microbiota function. Furthermore, they indicate that lysophospholipids play a pivotal role in lung-gut immune interactions. Our data also provide a potential microbiological monitoring strategy for people and animals subjected to cold-ammonia combined stress, which leads to intestinal metabolic dysfunction.