Abstract

Abstract Objectives Because dietary protein and carbohydrate levels impact the gastrointestinal (GI) microbiome and host metabolism, this study evaluated their effect on serum, urine and fecal metabolites. Methods Three complete and balanced isocaloric foods (mean 3940 kcals/kg) were used. Their protein (P) and carbohydrate (CHO) levels were: LP (P: 25.84%, CHO: 46.9%), MP (P: 32.0%, CHO: 39.9%) and HP (P: 50.67%, CHO: 21.2%). The study used 30 adult healthy cats and a balanced Latin-Square design. Food offering was adjusted to maintain weight; cats were fed for 80 days before receiving the next food. This study was reviewed and approved by IACUC and all cats included in this study were allowed routine social activities. Serum (S), urine (U) and fecal (F) samples were collected at the end of each treatment period and analyzed for non-targeted metabolomics by Metabolon Inc. (Morrisville, NC). Data analysis was performed by using JMP v14.0. Variables with significance at P < 0.05 are reported. Results PCA analysis of S, U and F metabolites together shows that the cats fed HP clustered separately from the cats fed LP and MP foods. Independent PCA analysis of S, U and F metabolites revealed that F metabolites show clear separation from the cats fed HP compared with LP and MP foods. However, S and U metabolites did not show this. Fecal samples showed that carbohydrates, acylglycerols, endocannabinoids and bile acids metabolism was significantly impacted by HP when compared with LP and MP foods. This resulted in elevations of a number of toxic metabolites (e.g., 3-indoxyl sulfate, p-cresol sulfate and trimethylamine N-oxide). The F concentration of these metabolites was positively correlated to that of S and U. This positive relationship in all three sample types was not observed for acylglycerols, endocannabinoids and sugars suggesting that those metabolites were not absorbed and excreted as were the mentioned toxins. Conclusions Dietary P and CHO levels influence cat's GI metabolism with impacting specific urine and serum metabolites. Cats fed HP food had F increases of toxic metabolites related to renal and cardiovascular disorders and these metabolites were positively associated with S and U concentrations. Dietary P and CHO levels may directly impact renal and cardiovascular disorders. Funding Sources Hill's Pet Nutrition, Inc.

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