Zhang Dongwei, Dong Biying, Chen Jie, Zhang Zhenqiang, Zeng Weitong, Liao Longxiong, Xiong Xia, Qin Xuejun, Fan Xianming
Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China.
Inflammation & Allergic Diseases Research Unit, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China.
Adv Biol (Weinh). 2025 Jun 27:e00028. doi: 10.1002/adbi.202500028.
This study evaluated the therapeutic effects of fecal microbiota transplantation (FMT) on lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS) in rats. The study focused on the balance of T-helper 17 (Th17) and regulatory T (Treg) cells, as well as the modulation of the JAK/STAT pathway. This study established a rat ARDS model using intranasal LPS instillation, administering interventions such as FMT, Treg cell depletion, and JAK inhibitors. Assessments included histopathological examination of lung and intestinal tissues, flow cytometry for Th17 and Treg cell proportions, qPCR and Western blot for gene and protein expression, ELISA for inflammatory cytokines, and correlation analysis using Spearman's method for cytokine-immune cell interactions. Results indicated that FMT and JAK inhibitors significantly reduce lung damage induced by LPS, reduced alveolar destruction and inflammation, restored Th17/Treg balance, and inhibited JAK/STAT pathway activity. Notably, FMT decreased pro-inflammatory cytokines (IL-2, IL-6, IL-8, IL-17A, IL-23, TGF-β1) and increased anti-inflammatory cytokines (IL-10, IL-35) in serum. Spearman correlation analysis indicated that FMT restored immune balance by modulating the interactions between cytokines and immune cells. In conclusion, FMT effectively alleviates lung and intestinal injury in LPS-induced ARDS rat models by modulating Th17/Treg balance and inhibiting JAK/STAT pathway activity, demonstrating promising therapeutic potential for ARDS treatment.
本研究评估了粪便微生物群移植（FMT）对脂多糖（LPS）诱导的大鼠急性呼吸窘迫综合征（ARDS）的治疗效果。该研究聚焦于辅助性T细胞17（Th17）和调节性T（Treg）细胞的平衡，以及JAK/STAT信号通路的调节。本研究通过鼻内滴注LPS建立大鼠ARDS模型，并给予FMT、Treg细胞耗竭和JAK抑制剂等干预措施。评估内容包括肺和肠道组织的组织病理学检查、Th17和Treg细胞比例的流式细胞术检测、基因和蛋白表达的qPCR及蛋白质免疫印迹分析、炎性细胞因子的酶联免疫吸附测定（ELISA），以及使用Spearman方法进行细胞因子 - 免疫细胞相互作用的相关性分析。结果表明，FMT和JAK抑制剂可显著减轻LPS诱导的肺损伤，减少肺泡破坏和炎症，恢复Th17/Treg平衡，并抑制JAK/STAT信号通路活性。值得注意的是，FMT可降低血清中促炎细胞因子（IL - 2、IL - 6、IL - 8、IL - 17A、IL - 23、TGF - β1）水平，并增加抗炎细胞因子（IL - 10、IL - 35）水平。Spearman相关性分析表明，FMT通过调节细胞因子与免疫细胞之间的相互作用恢复免疫平衡。总之，FMT通过调节Th17/Treg平衡和抑制JAK/STAT信号通路活性，有效减轻LPS诱导的ARDS大鼠模型的肺和肠道损伤，显示出在ARDS治疗中具有广阔的治疗潜力。
