Abstract

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.

Graphic abstract

中文翻译：

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大黄中含蒽醌的化合物可通过肠道微生物区系的功能改变防止吲哚生成

摘要

饮食中的色氨酸是由色氨酸酶在肠细菌（例如大肠杆菌）中产生吲哚产生的。。在肝脏中，吲哚被转化为硫酸吲哚酚，这是一种尿毒症毒素，是慢性肾脏疾病（CKD）的危险因素。益生菌和益生元目前用于抑制CKD，但尚无直接抑制吲哚产生的药物。在这项研究中，我们开发了一种优化的HPLC方法来分析吲哚生产，并通过改变肠道菌群来评估日粮和大黄对吲哚生产的影响。在高碳水化合物和高脂饮食喂养的小鼠中，吲哚的产生显着高于高纤维饮食喂养小鼠。我们进一步使用高碳水化合物饮食喂养的小鼠作为模型来研究大黄对吲哚生产的影响。大黄提取物的20％甲醇洗脱级分显着抑制了吲哚的产生，而洗脱液中的大黄酸8- O- β - d吡喃葡萄糖苷促成了浓度依赖的方式这种效应（RG）。RG的作用取决于蒽醌核心亚结构，即RG的糖苷配基部分（大黄酸），它似乎抑制了肠道菌群中的色氨酸酶功能。因此，除了较早的报道，大黄是一种有效的CKD治疗方法外，我们的研究还表明，大黄中的蒽醌部分可通过肠道微生物区系的功能性变化阻止尿毒症毒素的产生，从而抑制CKD的发展。

图形摘要