Department of Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.
Danone Nutricia Research, Uppsalalaan 12, Utrecht Science Park, 3584 CT Utrecht, The Netherlands.
Toxins (Basel). 2022 Sep 18;14(9):645. doi: 10.3390/toxins14090645.
Uremic metabolites, molecules either produced by the host or from the microbiota population existing in the gastrointestinal tract that gets excreted by the kidneys into urine, have significant effects on both health and disease. Tryptophan-derived catabolites are an important group of bacteria-produced metabolites with an extensive contribution to intestinal health and, eventually, chronic kidney disease (CKD) progression. The end-metabolite, indoxyl sulfate, is a key contributor to the exacerbation of CKD via the induction of an inflammatory state and oxidative stress affecting various organ systems. Contrastingly, other tryptophan catabolites positively contribute to maintaining intestinal homeostasis and preventing intestinal inflammation-activities signaled through nuclear receptors in particular-the aryl hydrocarbon receptor (AhR) and the pregnane X receptor (PXR). This review discusses the origins of these catabolites, their effect on organ systems, and how these can be manipulated therapeutically in the future as a strategy to treat CKD progression and gut inflammation management. Furthermore, the use of biotics (prebiotics, probiotics, synbiotics) as a means to increase the presence of beneficial short-chain fatty acids (SCFAs) to achieve intestinal homeostasis is discussed.
尿毒症代谢物是指由宿主产生或由胃肠道中存在的微生物群产生的分子，这些分子被肾脏排泄到尿液中，它们对健康和疾病都有重要影响。色氨酸衍生的代谢物是一类重要的细菌产生的代谢物，它们对肠道健康有广泛的贡献，最终对慢性肾脏病 (CKD) 的进展有影响。终末代谢产物吲哚硫酸酯是通过诱导炎症状态和氧化应激，影响各种器官系统，从而加剧 CKD 的关键因素。相比之下，其他色氨酸代谢物通过核受体（特别是芳香烃受体 (AhR) 和孕烷 X 受体 (PXR)）积极促进维持肠道内稳态和预防肠道炎症。本综述讨论了这些代谢物的来源、它们对器官系统的影响，以及未来如何通过操纵这些代谢物作为治疗 CKD 进展和肠道炎症管理的策略。此外，还讨论了使用生物制剂（益生元、益生菌、合生菌）作为增加有益短链脂肪酸 (SCFA) 存在的手段，以实现肠道内稳态。
