The effects of a hydrolyzed protein diet on the plasma, fecal and urine metabolome in cats with chronic enteropathy

Hydrolyzed protein diets are extensively used to treat chronic enteropathy (CE) in cats. However, the biochemical effects of such a diet on feline CE have not been characterized. In this study an untargeted (1)H nuclear magnetic resonance spectroscopy-based metabolomic approach was used to compare the urinary, plasma, and fecal metabolic phenotypes of cats with CE to control cats with no gastrointestinal signs recruited at the Royal Veterinary College (RVC). In addition, the biomolecular consequences of a hydrolyzed protein diet in cats with CE was also separately determined in cats recruited from the RVC (n = 16) and the University of Bristol (n = 24) and whether these responses differed between dietary responders and non-responders. Here, plasma metabolites related to energy and amino acid metabolism significantly varied between CE and control cats in the RVC cohort. The hydrolyzed protein diet modulated the urinary metabolome of cats with CE (p = 0.005) in both the RVC and Bristol cohort. In the RVC cohort, the urinary excretion of phenylacetylglutamine, p-cresyl-sulfate, creatinine and taurine at diagnosis was predictive of dietary response (p = 0.025) although this was not observed in the Bristol cohort. Conversely, in the Bristol cohort plasma betaine, glycerol, glutamine and alanine at diagnosis was predictive of outcome (p = 0.001), but these same results were not observed in the RVC cohort. The biochemical signature of feline CE in the RVC cohort was consistent with that identified in human and animal models of inflammatory bowel disease. The hydrolyzed protein diet had the same effect on the urinary metabolome of cats with CE at both sites. However, biomarkers that were predictive of dietary response at diagnosis differed between the 2 sites. This may be due to differences in disease severity, disease heterogeneity, factors unrelated to the disease or small sample size at both sites. As such, further studies utilizing larger number of cats are needed to corroborate these findings.