Gut-lung axis in equine asthma

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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.