Identification of Novel Biomarkers in Cats with Chronic Enteropathies

Abstract

Feline chronic enteropathy is a very common disorder with an increasing prevalence over the past decades. It mainly comprises idiopathic inflammatory bowel disease (IBD) and alimentary small cell lymphoma (SCL). Histopathology, immunohistochemistry, and clonality testing are currently considered to be the gold standard for the diagnosis and differentiation of IBD from SCL. The performance of these tests in a cohort of clinically healthy client-owned cats with similar demographic characteristics was evaluated. To characterize the mucosal proteome of cats with chronic enteropathy and to identify novel biomarker candidates, two-dimensional fluorescence difference gel electrophoresis was performed on intestinal biopsies. To characterize the fecal microbiome and metabolome, 16S rRNA sequencing and ultra-performance liquid chromatography were performed on fecal samples from cats with chronic enteropathy. Histopathology, immunohistochemistry, and clonality testing in healthy cats frequently revealed findings that are considered abnormal based on the currently accepted standards. Tests that are currently considered to be the gold standard for the diagnosis of feline chronic enteropathy should be interpreted with caution. Several potential protein biomarkers were identified in the intestinal mucosa of cats with CE. Among the identified proteins were those of the annexin and apolipoprotein families, and malate dehydrogenases. Characterization of the fecal microbiome of cats with chronic enteropathy revealed a dysbiosis pattern that has previously been described across different species with intestinal inflammation. The dysbiosis was characterized by a significantly reduced alpha diversity and trends for increased facultative anaerobic bacteria (e.g., Enterobacteriaceae) in favor of obligate anaerobic bacteria. However, the overall dysbiotic pattern did not differ between cats with IBD and cats with SCL. Characterization of the fecal metabolome revealed global metabolic changes in cats with chronic enteropathy with many pathways involved such as the tryptophan pathway, amino acids, sphingolipids, and sterols. However, the global metabolic pattern did not differ between cats with IBD and SCL. Further work is needed to verify these findings and confirm their promise for the development of a clinically useful biomarker or biomarker panel for the definitive diagnosis and sub-classification of feline chronic enteropathy.

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Keywords

Feline chronic enteropathy, inflammatory bowel disease, small cell lymphoma

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