Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan.
Stem Cell Research Center, National Yang-Ming University, Taipei 11221, Taiwan.
Cells. 2021 Jan 9;10(1):114. doi: 10.3390/cells10010114.
Chronic kidney disease (CKD) has long been known to cause significant digestive tract pathology. Of note, indoxyl sulfate is a gut microbe-derived uremic toxin that accumulates in CKD patients. Nevertheless, the relationship between gut microbiota, fecal indole content, and blood indoxyl sulfate level remains unknown. In our study, we established an adenine-induced CKD rat model, which recapitulates human CKD-related gut dysbiosis. Synbiotic treatment in CKD rats showed a significant reduction in both the indole-producing bacterium and fecal indole amount. Furthermore, gut microbiota diversity was reduced in CKD rats but was restored after synbiotic treatment. Intriguingly, in our end-stage kidney disease (ESKD) patients, the abundance of indole-producing bacteria, , , and , is similar to that of healthy controls. Consistently, the fecal indole tends to be higher in the ESKD patients, but the difference did not achieve statistical significance. However, the blood level of indoxyl sulfate was significantly higher than that of healthy controls, implicating that under an equivalent indole production rate, the impaired renal excretion contributes to the accumulation of this notorious uremic toxin. On the other hand, we did identify two short-chain fatty acid-producing bacteria, and , were reduced in ESKD patients as compared to the healthy controls. This may contribute to gut dysbiosis. We also identified that three genera Fusobacterium, Shewanella, and Erwinia, in the ESKD patients but not in the healthy controls. Building up gut symbiosis to treat CKD is a novel concept, but once proved effective, it will provide an additional treatment strategy for CKD patients.
慢性肾脏病（CKD）长期以来一直被认为会导致显著的消化道病理学改变。值得注意的是，硫酸吲哚酚是一种肠道微生物衍生的尿毒症毒素，在 CKD 患者中积累。然而，肠道微生物群、粪便吲哚含量和血液硫酸吲哚酚水平之间的关系尚不清楚。在我们的研究中，我们建立了腺嘌呤诱导的 CKD 大鼠模型，该模型再现了人类 CKD 相关的肠道菌群失调。CKD 大鼠的共生治疗显示，吲哚产生菌和粪便吲哚含量都显著减少。此外，CKD 大鼠的肠道微生物多样性减少，但共生治疗后恢复。有趣的是，在我们的终末期肾病（ESKD）患者中，吲哚产生菌、、、和的丰度与健康对照组相似。一致地，ESKD 患者的粪便吲哚含量较高，但差异没有达到统计学意义。然而，血液中硫酸吲哚酚的水平明显高于健康对照组，这表明在相同的吲哚产生率下，受损的肾脏排泄导致这种臭名昭著的尿毒症毒素的积累。另一方面，我们确实发现两种短链脂肪酸产生菌，和，在 ESKD 患者中减少，与健康对照组相比。这可能导致肠道菌群失调。我们还发现 ESKD 患者中有三个属的细菌，包括梭菌属、希瓦氏菌属和欧文氏菌属，但健康对照组中没有。建立肠道共生体来治疗 CKD 是一个新概念，但一旦被证明有效，它将为 CKD 患者提供另一种治疗策略。
