Gut-lung axis in equine asthma

马哮喘的肠肺轴

• 批准号: RGPIN-2020-06254
• 负责人: Leclère, Mathilde
• 金额: $ 2.4万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=760663
• 关键词: Gut; lung; axis; equine; asthma

GUT-LUNG AXIS IN EQUINE ASTHMA EQUINE ASTHMA IS A DEBILITATING DISEASE. More than 15% of domesticated adult horses suffer from severe asthma and at least twice as many are affected by milder forms. Equine asthma decreases the quality of life of affected horses and leads to early retirement and premature euthanasia. Inhalation of allergens present in hay triggers exacerbations characterized by coughing and labored breathing. In addition to allergens, certain disease-modifying factors can influence asthma severity (pollutants, tissue remodeling, microbes). There is increased evidence that the respiratory and gastrointestinal (GI) microbiota (i.e. all the bacteria living in the GI tract and the airways) are among these modulating factors. The GI microbiota acts as a modulator of immunity as bacterial fermentation of dietary fiber produces mediators such as short-chain fatty acids (SCFAs) that are absorbed in the bloodstream and can influence other organs from a distance. Asthmatic horses have less of these cellulolytic bacteria than healthy horses and humans with asthma have lower concentrations of SCFAs in their feces. The respiratory microbiota is believed to participate in maintaining a healthy lung environment and there are clear differences between the airway microbiota of people and horses with and without asthma. However, causality is difficult to establish because of the crosstalk between the microbiota and inflammation, and between the lungs and the GI tract. THE MAIN GOAL OF THIS RESEARCH PROGRAM is to determine if the GI microbiota of asthmatic horses contributes to systemic inflammation and airway dysfunction via decreased production of SCFAs. We also want to improve lung function during asthma attacks by transferring GI microbiota of healthy donors to asthmatic horses. Since the gut-lung crosstalk could go both ways, we will try to demonstrate that lung dysfunction can in return alter the respiratory and GI microenvironment and their microbial populations. SCIENTIFIC APPROACH. First, we will compare the GI microbiota and SCFAs of asthmatic and healthy horses. Second, we will determine if pulmonary and fecal microbiota change when horses transition from remission to exacerbation, in the absence of environmental or dietary changes. This will be possible using of a novel system that neutralizes inhalable dust from hay without changing its composition. Finally, we will determine whether fecal transplant from healthy donors decreases the severity of asthma exacerbations. NOVELTY AND EXPECTED SIGNIFICANCE. This work is important to veterinarians and owners of horses affected by this debilitating disease. It will also be useful to researchers working on the role of microbiota in asthma. If the role of the GI microbiota is confirmed and we show that it can be manipulated, fecal transplant could become a safe modulating therapy for equine asthma.

马哮喘是一种使人衰弱的疾病。超过15%的驯养成年马患有严重哮喘，至少有两倍的人患有轻度哮喘。马哮喘降低了受影响马匹的生活质量，并导致提前退休和过早安乐死。吸入干草中的过敏原会引发以咳嗽和呼吸困难为特征的病情恶化。除了过敏原，某些疾病修饰因素也会影响哮喘的严重程度（污染物、组织重塑、微生物）。越来越多的证据表明，呼吸和胃肠道（GI）微生物群（即生活在胃肠道和气道中的所有细菌）是这些调节因素之一。胃肠道微生物群是一种免疫调节剂，因为膳食纤维的细菌发酵会产生短链脂肪酸（SCFAs）等介质，这些介质被血液吸收，可以从远处影响其他器官。患有哮喘的马比健康的马含有更少的这些纤维素分解细菌，而患有哮喘的人的粪便中scfa的浓度更低。呼吸道微生物群被认为参与维持健康的肺部环境，患有哮喘和没有哮喘的人和马的呼吸道微生物群之间存在明显差异。然而，由于微生物群和炎症之间以及肺部和胃肠道之间的相互作用，很难确定因果关系。本研究计划的主要目的是确定哮喘马的胃肠道微生物群是否通过减少scfa的产生而导致全身炎症和气道功能障碍。我们还希望通过将健康供体的胃肠道微生物群转移到哮喘马身上来改善哮喘发作期间的肺功能。由于肠-肺串扰可能是双向的，我们将试图证明肺功能障碍可以反过来改变呼吸和胃肠道微环境及其微生物种群。科学的方法。首先，我们将比较哮喘和健康马的胃肠道微生物群和SCFAs。其次，我们将确定在没有环境或饮食改变的情况下，当马从缓解到恶化时，肺部和粪便微生物群是否会发生变化。这将有可能使用一种新的系统，它可以中和干草中的可吸入粉尘而不改变其成分。最后，我们将确定健康供体的粪便移植是否会降低哮喘恶化的严重程度。新颖性和预期意义。这项工作对兽医和马的主人来说很重要，他们的马受到这种使人衰弱的疾病的影响。这对研究微生物群在哮喘中的作用的研究人员也很有用。如果胃肠道微生物群的作用得到证实，我们表明它可以被操纵，粪便移植可能成为马哮喘的一种安全的调节疗法。