Changes in Proteins in Saliva and Serum in Equine Gastric Ulcer Syndrome Using a Proteomic Approach

SIMPLE SUMMARY: Equine gastric ulcer syndrome (EGUS) is a highly prevalent disease with a major clinical importance due to its negative effects on the welfare and performance of horses. EGUS can be distinguished into two different diseases depending on which anatomical region is affected: equine glandular gastric disease (EGGD), in which there is a lesion in the glandular stomach, and equine squamous gastric disease (ESGD), in which the alteration appears in the non-glandular stomach. EGUS has nonspecific clinical signs, and its underlying mechanism has not been completely elicited. Therefore, it would be of interest to clarify the pathophysiology and identify potential biomarkers of this syndrome. This study detected differences in the salivary and serum proteome between horses with EGUS and healthy horses, and also between horses with EGGD and ESGD. The most upregulated proteins in EGGD were related to the immune activation whereas, in horses with ESGD, the proteins with the most significant changes were associated with the squamous cell regulation and growth. Compared to serum, saliva had a higher number of proteins showing significant changes and also showed a different pattern of changes, indicating that the proteins in both fluids show a different response to the disease and can provide complementary information. ABSTRACT: Changes in the salivary proteome in 12 horses with the two diseases included in equine gastric ulcer syndrome (EGUS), equine glandular gastric disease (EGGD) (n = 6) and equine squamous gastric disease (ESGD) (n = 6), were evaluated using a high-resolution LC-MS/MS analysis of TMT-labelled peptides and compared to 10 healthy control horses. Serum was also analysed for comparative purposes. The comparison between the horses with EGGD and controls showed significant changes in 10 salivary proteins, whereas 36 salivary proteins were differently abundant between ESGD and control groups. The most upregulated proteins in the case of EGGD were related to immune activation whereas, in horses with ESGD, the most significantly changed proteins were associated with squamous cell regulation and growth. Compared to serum, saliva showed a higher number of proteins with significant changes and a different pattern of changes. The proteins identified in our study, in addition to providing new information about the pathophysiological mechanisms in these diseases, could have the potential to be novel biomarkers for the diagnosis or monitoring of EGGD and ESGD.