Lin Xuechun, Liang Wangqun, Li Li, Xiong Qianqian, He Shuiqing, Zhao Jing, Guo Xiaolei, Xiang Siyun, Zhang Piwei, Wang Hong, Ying Chenjiang, Yao Ying, Zuo Xuezhi
Department of Clinical Nutrition, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
J Ren Nutr. 2022 Sep;32(5):578-586. doi: 10.1053/j.jrn.2021.09.007. Epub 2021 Nov 2.
Indoxyl sulfate (IS) and p-cresyl sulfate (pCS) are two important gut microbiota-generated protein-bound uremic toxins. The present study aims to explore the alterations of serum IS and pCS concentrations, their production, and daily removal in end-stage renal disease (ESRD).
A case-controlled study was conducted based on 11 patients with ESRD and 11 healthy volunteers. The metabolic processes for IS and pCS were compared in these two groups, including gut microbiome, fecal indole and p-cresol, indole-producing bacteria and p-cresol-producing bacteria, serum total IS and pCS concentrations, and their daily removal by urine and spent dialyzate.
Compared with healthy controls, patients with ESRD exhibited higher relative abundance of the indole-producing bacteria Escherichia coli (P < .001) and Bacteroides fragilis (P = .010) and p-cresol-producing bacteria Bacteroides fragilis (P = .010) and Bacteroides caccae (P = .047). The predicted functional profiles of gut microbiome based on 16S rRNA gene PhyloChip analysis showed that the microbial tryptophan metabolism pathway (map00380, P = .0006) was significantly enriched in patients with ESRD. However, the fecal precursors indole (P = .332) and p-cresol concentrations (P = .699) were comparable between the two groups. The serum IS (P < .001) and pCS (P < .001) concentrations were far higher in patients with ESRD than those in healthy controls, whereas the daily total removal by urine and dialyzate was much lower for the former than that for the latter (P = .019 for IS, P = .016 for pCS).
The present study showed serious IS and pCS accumulation in patients with ESRD, with significant expansion of indole-producing bacteria and p-cresol-producing bacteria, upregulation of the bacterial tryptophan metabolism pathway, and greatly increased serum IS and pCS concentrations, whereas significant decline of daily IS and pCS removal.
硫酸吲哚酚（IS）和硫酸对甲酚（pCS）是两种由肠道微生物群产生的重要蛋白质结合尿毒症毒素。本研究旨在探讨终末期肾病（ESRD）患者血清IS和pCS浓度的变化、其产生及每日清除情况。
以11例ESRD患者和11名健康志愿者为基础进行病例对照研究。比较两组中IS和pCS的代谢过程，包括肠道微生物群、粪便吲哚和对甲酚、产吲哚细菌和产对甲酚细菌、血清总IS和pCS浓度，以及它们通过尿液和透析废液的每日清除量。
与健康对照相比，ESRD患者产吲哚细菌大肠杆菌（P <.001）和脆弱拟杆菌（P =.010）以及产对甲酚细菌脆弱拟杆菌（P =.010）和粪栖拟杆菌（P =.047）的相对丰度更高。基于16S rRNA基因PhyloChip分析的肠道微生物群预测功能谱显示，微生物色氨酸代谢途径（map00380，P =.0006）在ESRD患者中显著富集。然而，两组间粪便前体吲哚（P =.332）和对甲酚浓度（P =.699）相当。ESRD患者血清IS（P <.001）和pCS（P <.001）浓度远高于健康对照，而前者通过尿液和透析液的每日总清除量远低于后者（IS为P =.019，pCS为P =.016）。
本研究表明ESRD患者存在严重的IS和pCS蓄积，产吲哚细菌和产对甲酚细菌显著增多，细菌色氨酸代谢途径上调，血清IS和pCS浓度大幅升高，而IS和pCS的每日清除量显著下降。
