Indole is produced from dietary
tryptophan by
tryptophanase in intestinal bacteria, such as Escherichia coli. In the liver,
indole is converted into
indoxyl sulfate, a uremic toxin and risk factor for
chronic kidney disease (CKD). Probiotics and
prebiotics are currently used for suppressing CKD, but there are no drugs that directly suppress
indole production. In this study, we developed an optimized HPLC method for analyzing
indole production and evaluated the effect of diets and rhubarb on
indole production via the changes of gut microbiota. In high-
carbohydrate and high-fat diet-fed mice, the
indole production was significantly higher than in high-fiber diet-fed mice. We further used the high-
carbohydrate diet-fed mice as a model for examining the effect of rhubarb on
indole production. The 20%
methanol-eluted fraction of aqueous rhubarb extract significantly suppressed
indole production, and the eluate constituent
rhein 8-O-β-D-glucopyranoside (RG) contributed to this effect in a concentration-dependent manner. The effect of RG depended on the
anthraquinone core substructure, i.e., the aglycone moiety (
rhein) of RG, which appeared to inhibit the
tryptophanase function in gut microbiota. Thus, in addition to earlier reports that rhubarb is an effective CKD treatment, our study demonstrated that the
anthraquinone moiety in rhubarb prevents uremic toxin production via functional changes in gut microbiota, which suppresses CKD progression.