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: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=741120
• 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衰弱的疾病。超过15%的驯养成年马患有严重的哮喘，至少有两倍的人受到较轻形式的影响。马哮喘降低了受影响马的生活质量，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病情加重。除了过敏原，某些疾病修正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)微生物区系(即生活在胃肠道和呼吸道中的所有细菌)是这些调节因素之一。GI微生物区系起到免疫调节器的作用，因为膳食纤维的细菌发酵产生短链脂肪酸(SCFAs)等介质，这些介质被血液吸收，并可以远距离影响其他器官。患有哮喘的马比健康的马含有更少的这些纤维分解细菌，患有哮喘的人的粪便中的SCFAs浓度也更低。呼吸道微生物群被认为参与维持健康的肺部环境，患有哮喘和不患有哮喘的人和马的呼吸道微生物群之间存在明显的差异。然而，由于微生物区系和炎症之间，以及肺部和胃肠道之间的串扰，因果关系很难确定。该研究计划的主要目标是确定哮喘马的GI微生物区系是否通过减少SCFAs的产生而导致全身炎症和呼吸道功能障碍。我们还希望通过将健康捐赠者的GI微生物区系转移到哮喘马身上来改善哮喘发作期间的肺功能。由于肠道和肺的串扰可能是双向的，我们将试图证明肺功能障碍反过来可以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GI微生物区系和SCFAs。其次，在没有环境或饮食变化的情况下，我们将确定当马从缓解转变为恶化时，肺和粪便微生物区系是否会发生变化。这将有可能使用一种新的系统，在不改变其组成的情况下中和来自干草的可吸入粉尘。最后，我们将确定来自健康捐赠者的粪便移植是否可以降低哮喘恶化的严重程度。新颖性和预期意义。这项工作对兽医和受这种衰弱疾病影响的马匹的主人来说很重要。这也将对研究微生物区系在哮喘中的作用的研究人员有用。如果GI微生物区系的作用得到确认，并且我们证明它可以被操纵，粪便移植可能成为治疗马哮喘的一种安全的调节疗法。