Epigallocatechin-3-Gallate Decreases Plasma and Urinary Levels of p-Cresol by Modulating Gut Microbiota in Mice.

Abstract

p-Cresol (PC), a gut bacterial product of tyrosine catabolism, is recognized as a uremic toxin that has negative biological effects. Lowering the plasma PC level by manipulating the gut bacterial composition represents a promising therapeutic strategy in chronic kidney disease. This study was conducted to reveal whether epigallocatechin-3-gallate (EGCG) decreases plasma PC levels by limiting its bacterial production in a mouse model. The PC concentration in the samples was measured by high-performance liquid chromatography (HPLC) after treatments with sulfatase and β-glucuronidase. The results showed that the addition of EGCG to the diet decreased the plasma and urinary concentrations of PC in a dose-dependent manner, with a statistically significant difference between the control group and the 0.2% EGCG group. However, once EGCG was enzymatically hydrolyzed to epigallocatechin (EGC) and gallic acid, such effects were lost almost completely. The addition of 0.2% EGCG in the diet was accompanied by a decreased abundance of Firmicutes at the phylum level and Clostridiales at the order level, which constitute a large part of PC produced from tyrosine. In conclusion, EGCG, not EGC, reduced plasma and urinary concentrations of PC in mice by suppressing its bacterial production with accompanying alteration of the relative abundance of PC producers.