Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran; Department of Pathology, University of California San Francisco, San Francisco, US.
B.S, Department of Microbiology and Microbial Biotech, Shahid Beheshti University, Tehran, Iran.
Biomed Pharmacother. 2024 Nov;180:117571. doi: 10.1016/j.biopha.2024.117571. Epub 2024 Oct 17.
Pulmonary fibrosis (PF) is a progressive and debilitating respiratory condition characterized by excessive deposition of extracellular matrix proteins and scarring within the lung parenchyma. Despite extensive research, the pathogenesis of PF remains incompletely understood, and effective therapeutic options are limited. Emerging evidence suggests a potential link between gut microbiota dysbiosis and the development of PF, highlighting the gut-lung axis as a promising therapeutic target. Akkermansia muciniphila (A. muciniphila), a mucin-degrading bacterium residing in the gut mucosal layer, has garnered considerable interest due to its immunomodulatory and anti-inflammatory properties. This study investigates the therapeutic potential of live and pasteurized A. muciniphila, as well as its extracellular vesicles (EVs), in mitigating inflammation and fibrosis in a murine model of carbon tetrachloride (CCl4)-induced PF exacerbated by a high-fat diet (HFD). Male C57BL/6 mice were divided into groups receiving either a normal diet or an HFD, with or without CCl4 administration. The mice were then treated with live or pasteurized A. muciniphila, or its EVs. Lung tissue was analyzed for the expression of inflammatory markers and fibrosis markers using real-time PCR and ELISA. Administration of live and pasteurized A. muciniphila, as well as its EVs, significantly downregulated the expression of inflammatory and fibrosis markers in the lung tissue of CCl4-induced PF mice. Furthermore, these treatments ameliorated the increased production of IL-6 and reduced IL-10 levels observed in the HFD and CCl4-treated groups. These findings suggest that A. muciniphila and its derivatives exert protective effects against pulmonary inflammation and fibrosis, potentially through modulation of the gut-lung axis. The study highlights the therapeutic potential of A. muciniphila and its derivatives as novel interventions for the management of PF, warranting further preclinical and clinical investigations.
肺纤维化（PF）是一种进行性和使人虚弱的呼吸系统疾病，其特征是肺实质中细胞外基质蛋白的过度沉积和瘢痕形成。尽管进行了广泛的研究，但 PF 的发病机制仍不完全清楚，有效的治疗选择有限。新出现的证据表明，肠道微生物失调与 PF 的发生之间可能存在潜在联系，突出了肠道-肺部轴作为有前途的治疗靶点。栖粪杆菌（A. muciniphila），一种存在于肠道黏膜层的粘蛋白降解菌，由于其免疫调节和抗炎特性而引起了相当大的关注。本研究调查了活菌和巴氏杀菌的 A. muciniphila 及其细胞外囊泡（EVs）在减轻由高脂肪饮食（HFD）加重的四氯化碳（CCl4）诱导的 PF 小鼠模型中的炎症和纤维化的治疗潜力。雄性 C57BL/6 小鼠分为接受正常饮食或 HFD 的组，或接受或不接受 CCl4 处理。然后用活菌或巴氏杀菌的 A. muciniphila 或其 EVs 治疗小鼠。使用实时 PCR 和 ELISA 分析肺组织中炎症标志物和纤维化标志物的表达。活菌和巴氏杀菌的 A. muciniphila 及其 EVs 的给药显著下调了 CCl4 诱导的 PF 小鼠肺组织中炎症和纤维化标志物的表达。此外，这些治疗方法改善了在 HFD 和 CCl4 处理组中观察到的 IL-6 增加和 IL-10 水平降低。这些发现表明 A. muciniphila 及其衍生物对肺炎症和纤维化具有保护作用，可能通过调节肠道-肺部轴。该研究强调了 A. muciniphila 及其衍生物作为治疗 PF 的新型干预措施的治疗潜力，值得进一步进行临床前和临床研究。
