Lai Yitian, Qiu Ranran, Zhou Jingying, Ren Ling, Qu Yizhuo, Zhang Guoshan
College of Acupuncture-Moxibustion-Tuina and Rehabilitation, Hunan University of Chinese Medicine, Changsha, 410208, China.
The First Hospital of Hunan University of Chinese Medicine, Changsha, 410007, China.
Inflammation. 2025 Jan 7. doi: 10.1007/s10753-024-02233-w.
Asthma is a prevalent chronic inflammatory disorder of the respiratory tract that not only manifests with respiratory symptoms but also often involves intestinal flora disorders and gastrointestinal dysfunction. Recent studies have confirmed the close relationship between the gut and lungs, known as the "gut-lung axis" theory. Fecal microbiota transplantation (FMT), a method for restoring normal intestinal flora, has shown promise in treating common gastrointestinal diseases. The "gut-lung axis" theory suggests that FMT may have significant therapeutic potential for asthma. In this study, we established an Ovalbumin (OVA)-induced rat model of asthma to investigate the protective effect of FMT on airway inflammation and the restoration of intestinal short-chain fatty acids (SCFAs), aiming to explore its underlying mechanism. Rats in the Control group underwent fecal treatment via gavage (Control-FMT, C-FMT group), while rats in the Asthma group underwent fecal treatment via gavage after asthma induction (Asthma-FMT, A-FMT group). Following a two-week period of continuous intragastric administration, various measurements were conducted to assess pulmonary function, peripheral blood neutrophil, lymphocyte, and eosinophil content, lung tissue pathology, and collagen fiber deposition in the lungs. Additionally, neutrophil and eosinophil content in bronchoalveolar lavage fluid (BALF), expression levels of Interleukin-4 (IL-4), IL-5, IL-13, IL-17, IL-33, leukotrienes (LT), thymic stromal lymphopoietin (TSLP), prostaglandin D2 (PGD2) protein and mRNA in lung tissue, and SCFAs content in stool were evaluated. In the C-FMT group, lung function significantly improved, inflammatory cell content in peripheral blood and BALF decreased, lung tissue pathology and collagen fiber deposition significantly improved, the protein and mRNA levels of lung inflammatory factors IL-4, IL-5, IL-13, IL-17, IL-33, LT, TSLP, PGD2 were significantly decreased, and SCFAs such as acetate (C2), propionate (C3), butyrate (C4), isobutyric acid (I-C4), valeric acid (C5), and isovaleric acid (I-C5) content in stool significantly increased. However, the indexes in the A-FMT group did not show significant recovery, and the treatment effect on asthma symptoms in rats was inferior to that in the C-FMT group. Asthma induced intestinal flora disorders in rats, and FMT treatment improved the inflammatory response in asthmatic rat models and corrected their intestinal SCFAs disorders. Encouraging the recovery of intestinal SCFAs may play a significant role, and beneficial bacteria present in feces may improve asthma symptoms by promoting the remodeling of intestinal flora. This experiment provides further scientific evidence supporting the "gut-lung axis" theory.
哮喘是一种常见的呼吸道慢性炎症性疾病，不仅表现为呼吸道症状，还常伴有肠道菌群紊乱和胃肠功能障碍。最近的研究证实了肠道与肺部之间的密切关系，即“肠-肺轴”理论。粪便微生物群移植（FMT）是一种恢复正常肠道菌群的方法，已显示出在治疗常见胃肠疾病方面的潜力。“肠-肺轴”理论表明，FMT可能对哮喘具有显著的治疗潜力。在本研究中，我们建立了卵清蛋白（OVA）诱导的大鼠哮喘模型，以研究FMT对气道炎症的保护作用以及肠道短链脂肪酸（SCFAs）的恢复情况，旨在探索其潜在机制。对照组大鼠通过灌胃进行粪便处理（对照-FMT，C-FMT组），而哮喘组大鼠在诱导哮喘后通过灌胃进行粪便处理（哮喘-FMT，A-FMT组）。经过两周的连续胃内给药后，进行了各种测量，以评估肺功能、外周血中性粒细胞、淋巴细胞和嗜酸性粒细胞含量、肺组织病理学以及肺中胶原纤维沉积情况。此外，还评估了支气管肺泡灌洗液（BALF）中的中性粒细胞和嗜酸性粒细胞含量、肺组织中白细胞介素-4（IL-4）、IL-5、IL-13、IL-17、IL-33、白三烯（LT）、胸腺基质淋巴细胞生成素（TSLP）、前列腺素D2（PGD2）蛋白和mRNA的表达水平，以及粪便中SCFAs的含量。在C-FMT组中，肺功能显著改善，外周血和BALF中的炎症细胞含量降低，肺组织病理学和胶原纤维沉积显著改善，肺炎症因子IL-4、IL-5、IL-13、IL-17、IL-33、LT、TSLP、PGD2的蛋白和mRNA水平显著降低，粪便中乙酸（C2）、丙酸（C3）、丁酸（C4）、异丁酸（I-C4）、戊酸（C5）和异戊酸（I-C5）等SCFAs含量显著增加。然而，A-FMT组的指标未显示出明显恢复，对大鼠哮喘症状的治疗效果低于C-FMT组。哮喘诱导了大鼠肠道菌群紊乱，FMT治疗改善了哮喘大鼠模型中的炎症反应并纠正了其肠道SCFAs紊乱。促进肠道SCFAs的恢复可能发挥重要作用，粪便中存在的有益细菌可能通过促进肠道菌群重塑来改善哮喘症状。本实验为“肠-肺轴”理论提供了进一步的科学证据。
