Microbial Indole Catabolites of Tryptophan in Cats with Chronic Enteropathy

Abstract: Background: Inflammatory bowel disease (IBD) and alimentary small cell lymphoma (SCL) are common chronic enteropathies (CE) in cats. Enteric microbiota dysbiosis is implicated in the pathogenesis of CE, but mechanisms of host-microbiome interactions are poorly understood. Microbial indole catabolites of tryptophan (MICT) are gut microbial metabolites that participate in regulating mucosal barrier function and inflammation in humans and rodents. Previous metabolomic studies identified altered microbial tryptophan metabolism in cats with CE.

Hypothesis/Objectives: Quantify MICTs in sera of cats with IBD or SCL and compare them to healthy controls. We hypothesized that MICT concentrations would be decreased in cats with IBD or SCL compared with healthy controls.

Animals: Archived serum from cats with histopathological diagnoses of IBD (n=44) or SCL (n=31), and healthy controls (n=51).

Methods: Quantitative LC-MS was used to measure serum concentrations of tryptophan and seven different MICT metabolites.

Results: Serum concentrations of tryptophan, indolepropionate, indoleacrylate, indolelactate, indolepyruvate, and indolealdehyde varied significantly (Kruskal-Wallis P < .05) among groups and were significantly (post-hoc Dunn Padj < .05) decreased in the IBD and SCL groups compared to healthy controls. Indolelactate concentrations were significantly decreased in the sera of cats with SCL compared to IBD (Padj=.0061), but no other analytes differed significantly between these groups.

Conclusions and Importance: Consistent with studies in humans and laboratory animals, our findings suggest microbial catabolism of tryptophan is decreased in cats with CE. MICTs are promising biomarkers that can be used to investigate the pathophysiologic consequences of dysbiosis in cats with IBD and SCL.