Background: Single-lung ventilation (SLV), commonly used in thoracic surgery, carries a risk of acute lung injury and acute respiratory distress syndrome. Our previous studies suggest that pulmonary microbiota may play a role in SLV-induced lung injury, but the precise mechanisms remain unclear. Palmitoleic acid (PoA), a crucial metabolite, is associated with protective physiological processes. This study explores the variations in pulmonary microbiota and metabolites during SLV-induced lung injury and investigates the potential protective role of PoA.
Results: The development of SLV-induced lung injury correlated with the changes of pulmonary microbiota and alterations of certain microbial genera and species. Through metabolomics and correlation analysis of pulmonary metabolites and microbiota, several metabolites exhibited a negative association with SLV-induced lung injury, with PoA being particularly noteworthy. Changes in pulmonary microbiota appeared to contribute to the reduction of PoA levels, ultimately leading to lung injury. Supplementation with PoA significantly attenuated the severity of lung injury, both in vivo and in vitro, by upregulating PPARγ expression and its downstream signaling pathways.
Conclusions: The dysregulation of pulmonary microbiota contributes to SLV-induced lung injury, with PoA reduction playing a role in this process. PoA supplementation offers a protective effect by activating the PPAR pathway, suggesting its therapeutic potential in mitigating SLV-induced lung injury.
Keywords: PPAR; lung injury; palmitoleic acid; pulmonary microbiota; single-lung ventilation.
© The Author(s) 2026. Published by Oxford University Press on behalf of the American Thoracic Society.