粪便菌群移植通过增加肠道短链脂肪酸水平缓解哮喘大鼠气道炎症。

IF 4.5 2区 医学 Q2 CELL BIOLOGY Inflammation Pub Date : 2025-01-07 DOI:10.1007/s10753-024-02233-w
Yitian Lai, Ranran Qiu, Jingying Zhou, Ling Ren, Yizhuo Qu, Guoshan Zhang
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引用次数: 0

摘要

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,还常涉及肠道菌群紊乱和胃肠道功能障碍。最近的研究证实了肠道和肺之间的密切关系,被称为“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,在治疗常见胃肠道疾病方面显示出前景。“肠-肺轴”理论表明,FMT可能对哮喘有显著的治疗潜力。本研究通过建立卵清蛋白(OVA)诱导的哮喘大鼠模型,研究FMT对气道炎症和肠道短链脂肪酸(SCFAs)恢复的保护作用,探讨其机制。对照组采用灌胃方式处理粪便(Control- fmt, C-FMT组),哮喘组采用诱导哮喘后灌胃处理粪便(Asthma- fmt, A-FMT组)。连续灌胃给药两周后,进行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、肺组织病理学和肺内胶原纤维沉积。测定支气管肺泡灌洗液(BALF)中中性粒细胞和嗜酸性粒细胞的含量,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。C-FMT组肺功能显著改善,外周血炎症细胞含量及BALF降低,肺组织病理及胶原纤维沉积明显改善,肺炎性因子IL-4、IL-5、IL-13、IL-17、IL-33、LT、TSLP、PGD2蛋白及mRNA水平显著降低,SCFAs如乙酸(C2)、丙酸(C3)、丁酸(C4)、异丁酸(I-C4)、戊酸(C5)、粪便中异戊酸(I-C5)含量显著升高。但A-FMT组各项指标未见明显恢复,对大鼠哮喘症状的治疗效果也不如C-FMT组。哮喘引起的大鼠肠道菌群紊乱,FMT治疗可改善哮喘大鼠模型的炎症反应,纠正其肠道SCFAs紊乱。促进肠道短链脂肪酸的恢复可能发挥重要作用,粪便中存在的有益菌可能通过促进肠道菌群的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依据。
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Fecal Microbiota Transplantation Alleviates Airway Inflammation in Asthmatic Rats by Increasing the Level of Short-Chain Fatty Acids in the Intestine.

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.

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来源期刊
Inflammation
Inflammation 医学-免疫学
CiteScore
9.70
自引率
0.00%
发文量
168
审稿时长
3.0 months
期刊介绍: Inflammation publishes the latest international advances in experimental and clinical research on the physiology, biochemistry, cell biology, and pharmacology of inflammation. Contributions include full-length scientific reports, short definitive articles, and papers from meetings and symposia proceedings. The journal''s coverage includes acute and chronic inflammation; mediators of inflammation; mechanisms of tissue injury and cytotoxicity; pharmacology of inflammation; and clinical studies of inflammation and its modification.
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