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: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=718272
• 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.

马哮喘的肠-肺轴 马哮喘是一种使人衰弱的疾病。超过15%的驯化成年马患有严重哮喘，至少有两倍的人受到轻度哮喘的影响。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。吸入干草中存在的过敏原会引发以咳嗽和呼吸困难为特征的急性发作。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，呼吸道和胃肠道（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。胃肠道微生物群作为免疫调节剂，因为膳食纤维的细菌发酵产生介质，如短链脂肪酸（SCFA），这些介质在血流中被吸收，并可以从远处影响其他器官。患有哮喘的马比健康的马有更少的这些纤维素分解细菌，患有哮喘的人在他们的粪便中有更低浓度的SCFA。呼吸道微生物群被认为参与维持健康的肺部环境，并且患有和不患有哮喘的人和马的气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串扰，因果关系难以确定。 本研究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捐赠者的胃肠道微生物群转移到哮喘马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，因此我们将尝试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，我们将比较哮喘马和健康马的胃肠道微生物群和SCFA。其次，我们将确定在没有环境或饮食变化的情况下，当马从缓解过渡到恶化时，肺部和粪便微生物群是否发生变化。这将是可能的使用一种新的系统，中和可吸入的灰尘从干草，而不改变其组成。最后，我们将确定从健康供体的粪便移植是否降低哮喘急性发作的严重程度。 新奇和预期意义。这项工作对兽医和受这种使人衰弱的疾病影响的马的主人很重要。它也将有助于研究微生物群在哮喘中的作用的研究人员。如果胃肠道微生物群的作用得到证实，并且我们证明它可以被操纵，粪便移植可能成为马哮喘的安全调节疗法。