近日，
研究团队发现，在腺嘌呤诱导的CKD小鼠中，硫酸吲哚酚清除受损会升高粘膜诱导型一氧化氮合酶（iNOS）基因的表达。由此产生的肠道硝酸盐水平的上升通过硝酸盐呼吸作用促进了大肠杆菌的生长。在厌氧培养过程中，CKD患者的粪便微生物群比健康对照组的粪便产生更多的吲哚，但仅在硝酸盐存在的情况下。硝酸盐促进大肠杆菌产生吲哚，从而恶化CKD小鼠的肾脏病理，而iNOS抑制可以减轻这种情况。
据悉，慢性肾脏疾病（CKD）与肠杆菌科粪便丰度升高有关，但这种转变的生态驱动因素及其对疾病进展的影响尚不清楚。尿毒症毒素硫酸吲哚是由肝脏中微生物衍生的吲哚产生的。
附：英文原文
Title: Host-derived nitrate fuels indole production by Escherichia coli to drive chronic kidney disease progression
Author: Jee-Yon Lee, Scott P. Mahan, Thaynara Parente de Carvalho, Henry Nguyen, Chonikarn Singai, Lizbeth Camacho, Mert Tekeli, Yu-Jin Kwon, Ji-Won Lee, Renato L. Santos, Renée M. Tsolis, Sebastian E. Winter, Andreas J. Bumler
Issue&Volume: 2026-03-19
Abstract: Chronic kidney disease (CKD) is linked to an elevated fecal abundance of Enterobacteriaceae, but the ecological drivers of this shift and its impact on disease progression remain unclear. The uremic toxin indoxyl sulfate is produced from microbiota-derived indole in the liver. Here, we found that in mice with adenine-induced CKD, impaired clearance of indoxyl sulfate elevated mucosal expression of the gene encoding inducible nitric oxide synthase (iNOS). The resulting rise in luminal nitrate levels promoted Escherichia coli growth by means of nitrate respiration. Fecal microbiota from CKD patients generated more indole than feces of healthy controls during anaerobic culture, but only in the presence of nitrate. Nitrate enhanced indole production by E. coli, thereby worsening renal pathology in CKD mice, which was mitigated by iNOS inhibition.
DOI: ady5217
Source: https://www.science.org/doi/10.1126/science.ady5217