CLINICAL AND CLINICOPATHOLOGICAL CHARACTERIZATION OF CANINE CHRONIC ENTEROPATHY: THE IN-FIELD EVALUATION OF INFLAMMATORY, MICROBIOMIC AND METABOLOMIC PROFILES

Chronic inflammatory enteropathies (CIEs) are a group of diseases characterized by chronic gastrointesnal (GI) signs, last for >3 weeks. Once extra-gastrointesnal causes of GI signs have been ruled out, CIEs are classified based on therapeuc response to diet or medical trials. Among them, inflammatory protein-losing enteropathy (iPLE) is disnguished by the loss of proteins into the intesnal lumen, a condion associated with a poor prognosis. Although several studies have idenfied protein loss as a negave prognosc factor, the underlying mechanisms leading to iPLE development remain poorly understood. Understanding the pathogenesis of CIEs and iPLE is fundamental for correct diagnosc and therapeuc management. Clinically useful biomarkers are essenal for diagnosing, staging, and monitoring treatment in both canine CIEs and iPLE. Different potenal markers have been invesgated over the years to help the clinician in the diagnosis and the determinaon of the disease severity, however, none of these is highly sensive and specific, highlighng the need for targeted, reliable, and minimally invasive markers that are cost-effecve and clinically useful. This study aims to clinically and clinicopathologically characterize iPLE, with a parcular focus on lipid dysmetabolism markers. In the first part of the research, a retrospecve analysis was conducted on laboratory results and medical records of dogs with iPLE to idenfy potenal new hematological markers and outcome predictors. The study found that dogs with iPLE exhibited significantly altered neutrophil-to-lymphocyte raos, albuminto- globulin raos and C-reacve protein to albumin raos, and that albumin to globulin rao and C-reacve protein to albumin rao are potenally more appropriate markers of disease severity and treatment efficacy than NLR in dogs with iPLE. The second phase prospecvely evaluated lipid dysmetabolism in iPLE dogs, assessing serum and fecal lipid markers before and a5er one month of therapy. The hypothesis was that dogs with iPLE suffer from lipid dysmetabolism that may play a key role in the pathogenesis of the disease. For this second part a populaon of dogs with iPLE were prospecvely enrolled. A mul-omic approach was applied to fecal samples, examining the microbiota and metabolome, while serum lipoproteins and fat-soluble vitamins were analyzed in the same populaon. Results revealed a not constant pa7ern of dysbiosis in the populaon of dogs with iPLE, but significant alteraons in fecal bile acid and sterols profiles and an increase in fecal longchain fa7y acids, suggesng an impaired lipid absorpon process. Addionally, serum analysis showed a marked decrease in high-density lipoproteins and fat-soluble vitamins, reinforcing the hypothesis of lipid malabsorpon and dysregulaon in iPLE. The findings of this study enhance our understanding of the pathophysiology of iPLE, highlighng the significance of lipid metabolism alteraons in this complex GI disease. The results provide a foundaon for future research, exploring new potenal dietary and therapeuc strategies to improve lipid homeostasis and disease management