铜绿假单胞菌是院内常见的耐药致病菌，所引起的肺炎临床预后不佳。研究发现调节体内菌群可预防铜绿肺炎的发生，且菌群特征与预后相关。但菌群影响宿主的机制不明确。我们的研究证实铜绿患者肺内菌群与肺炎严重程度相关；综合分析菌群和宿主的代谢信息发现死亡患者肺内菌群代谢γ亚麻酸（GLA）/磷脂的活性降低；以GLA干预铜绿肺炎小鼠可减轻炎症损伤，伴有肺泡巨噬细胞（AMs）数量的增加。由此，我们推论肺内菌群GLA/磷脂代谢或通过促进AMs功能，减轻肺部炎症损伤，且菌群或可调节肺内脂质代谢。本课题拟通过临床、动物、细胞等多层面①确认铜绿患者肺内菌群脂质代谢与AMs功能及预后相关；②明确增强肺内GLA/磷脂代谢可促进AMs的免疫功能以减轻炎症；且脂质代谢可能通过PPARγ信号通路调控AMs功能；③初步明确肺内菌群对GLA/磷脂代谢的调节作用。本课题立足于肺内菌群脂质代谢的功能，为该类感染的治疗探索新策略。

Pseudomonas aeruginosa is a common drug-resistant pathogen in the hospital, and the clinical prognosis of pneumonia caused by it is worse. Previous studies have shown that regulation of the host’s microbiota can prevent the occurrence of Pseudomonas aeruginosa pneumonia. It was also found that microbial composition was related to the prognosis of those patients. However, the mechanism is not clear. Our previous study confirmed that ① the lower respiratory tract microbiota was associated with the severity of Pseudomonas aeruginosa pneumonia, ② the lung microbiota-associated gamma linolenic acid (GLA)/phospholipid was decreased in the lungs of the dead patients, ③ GLA intervention could reduce lung damage with an increase of the number of alveolar macrophages (AMs). We hypothesize that lung microbiota-associated GLA/phospholipid metabolism could promote AMs function, alleviate lung damage, and regulate lung lipid metabolism. We plan to design experiments to ① confirm that the lipid metabolism in the lungs of Pseudomonas aeruginosa patients was associated with AMs function and patients’ prognosis, ② validate that enhancing GLA/phospholipid metabolism in the lung can promote the AMs function through PPAR-γ signaling pathway, ③ investigate whether lung microbiota could regulate GLA/phospholipid metabolism in the lung. Our project is based on the function of lipid metabolism in the lungs and tries to explore new strategies for the treatment of pneumonia caused by Pseudomonas aeruginosa.