The Effect of Dietary Protein Concentration on the Fecal Microbiome and Serum Concentrations of Gut-Derived Uremic Toxins in Healthy Adult Cats

SIMPLE SUMMARY: Dietary formulation can affect the composition of the microbes that reside in the gut and microbial products. Some microbial products are toxins that can accumulate in the systemic circulation of cats with a disturbed gut microbial community. Indoxyl sulfate, p-cresol sulfate, and trimethylamine-n-oxide are toxins produced during microbial fermentation of protein in the gut. By changing the gut microbial community, dietary protein concentration could affect the production of these toxins. The purpose of this study was to evaluate the effect of feeding healthy adult cats with foods containing variable protein concentrations for 3 months on the fecal microbiome and serum concentrations of the major gut-derived toxins. We found that cats fed a high-protein diet had increasing serum concentrations of p-cresol sulfate in the first 8 weeks before returning to baseline concentrations. Cats fed a high-protein diet also had increased diversity of the fecal microbial community and reduced relative abundance of beneficial bacteria in the Bifidobacterium genus. ABSTRACT: The purpose of this study was to evaluate the effect of feeding healthy adult cats with foods containing variable protein concentrations on the fecal microbiome and serum concentrations of the gut-derived uremic toxins indoxyl sulfate, p-cresol sulfate (pCS), and trimethylamine-n-oxide. Twenty healthy young adult cats were randomized into two groups and fed either a low-protein diet (LPD; 7.4 g/100 kcal ME) or a high-protein diet (HPD; 11.0 g/100 kcal ME) for a 12-week period. Serum uremic toxin concentrations were measured via liquid chromatography tandem mass spectrometry, and the fecal microbiome was characterized using shallow sequence shotgun metagenomics. Cats that consumed the HPD had higher pCS concentrations at 8 weeks (p = 0.028) when compared to baseline. After 12 weeks, cats fed the HPD had higher fecal alpha diversity indices at both the taxonomic and functional levels and lower fecal Bifidobacterium relative abundance compared to those cats fed the LPD. In conclusion, a change in diet and dietary protein concentration shifted the fecal microbial community and microbial function. Feeding cats a high amount of protein increased serum concentrations of the uremic toxin pCS; however, the effect was short-lived.