The beneficial effects of Akkermansia muciniphila and its derivatives on pulmonary fibrosis.

Shahrbanoo Keshavarz Aziziraftar, Romina Bahrami, Danial Hashemi, Arefeh Shahryari, Amitis Ramezani, Fatemeh Ashrafian, Seyed Davar Siadat
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Abstract

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.

Akkermansia muciniphila 及其衍生物对肺纤维化的有益作用。
肺纤维化(PF)是一种进行性衰弱呼吸系统疾病,其特征是肺实质内细胞外基质蛋白过度沉积和瘢痕形成。尽管进行了广泛的研究,但人们对肺纤维化的发病机理仍不完全了解,有效的治疗方案也很有限。新出现的证据表明,肠道微生物群失调与肺结核的发病之间存在潜在联系,这凸显了肠道-肺轴是一个很有前景的治疗靶点。Akkermansia muciniphila(A. muciniphila)是一种栖息于肠道粘膜层的粘蛋白降解菌,因其免疫调节和抗炎特性而备受关注。本研究调查了活体和巴氏灭菌粘液噬菌体及其胞外囊泡(EVs)在四氯化碳(CCl4)诱导、高脂饮食(HFD)加重的小鼠 PF 模型中减轻炎症和纤维化的治疗潜力。雄性 C57BL/6 小鼠被分为两组,一组接受正常饮食,另一组接受高脂饮食,同时接受或不接受 CCl4 给药。然后用活的或巴氏灭菌的粘液虹彩病毒或其 EVs 对小鼠进行处理。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。在 CCl4 诱导的 PF 小鼠肺组织中,注射活的和巴氏灭菌的粘液虹吸虫及其 EVs 能显著降低炎症标记物和纤维化标记物的表达。此外,这些处理还改善了高纤维食物组和 CCl4 处理组中观察到的 IL-6 生成增加和 IL-10 水平降低的情况。这些发现表明,A. muciniphila 及其衍生物对肺部炎症和纤维化具有保护作用,这可能是通过调节肠道-肺轴实现的。该研究强调了粘菌素及其衍生物作为治疗肺纤维化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。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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