Low temperatures enhance PM2.5-mediated mitochondrial dysfunction in the pig lung-intestinal axis, causing damage to the gut

INTRODUCTION: Fine particulate matter (PM2.5) is a major airborne pollutant in low-temperature livestock housing. Individual environmental factors have been widely studied. However, the actual growth environments of livestock and poultry usually involve the combined effects of multiple environmental factors. OBJECTIVES: This study aims to investigate the fundamental mechanisms underlying energy metabolism disorders in the lung-intestine axis of finishing pigs under the combined effects of low temperature and PM2.5. METHODS: This study characterized the physical, chemical, and microbial composition of the PM2.5 collected from pig houses. Inflammatory responses and energy metabolism were assessed at the tissue level. Key signaling pathways were functionally validated using in vitro cell models. Analysis of the lung-gut transcriptome elucidated the specific mechanisms by which the lung-gut axis responds to adverse environmental injuries. RESULTS: This study found that PM2.5 affects the energy metabolism process of lung macrophages, and low temperatures exacerbate the effects of PM2.5. Environmental factors trigger lactate production and mitochondrial dysfunction in macrophages through the HIF-PDK pathway. This dysfunction results in the release of pro-inflammatory factors that mediate systemic inflammation. Elevated levels of intestinal injury markers detected in serum indicate intestinal damage. Lung-gut transcriptomic analysis revealed impairments in immune and metabolic pathways. These findings were validated in intestinal tissues, supporting the activation of the lung-gut axis, which mediates systemic inflammation and intestinal damage following respiratory exposure. CONCLUSION: In summary, these findings elucidate the specific mechanisms through which combined cold exposure and PM2.5 exposure disrupt pulmonary and intestinal immune-metabolic homeostasis. This underscores the necessity of implementing interventions in intensive livestock production systems.