Effects of the oral adsorbent AST-120 on fecal p-cresol and indole levels and on the gut microbiota composition
Effects of the oral adsorbent AST-120 on fecal p-cresol and indole levels and on the gut microbiota composition
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DOI：
10.1016/j.bbrc.2020.02.141
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发表时间：
2020-05-07
影响因子：
3.1
通讯作者：
Takahashi, Nobuyuki
中科院分区：
文献类型：
--
作者：
Sato, Emiko;Hosomi, Koji;Takahashi, Nobuyuki
在慢性肾脏疾病中，循环尿毒症毒素水平升高与各种症状和器官功能障碍相关。硫酸吲哚酚（IS）和硫酸对甲苯酯（pCS）是微生物衍生的代谢产物和代表性尿毒症毒素。我们以前已经表明，口服吸附剂AST 120深刻降低pCS相比，在腺嘌呤诱导的肾功能衰竭小鼠的IS。然而，AST-120在IS和pCS之间的不同衰减效应的机制尚不清楚。为了阐明AST-120对IS和pCS的差异，我们研究了粪便吲哚和对甲酚（IS和pCS各自的前体）的水平，并检查了对肠道微生物群的影响。尽管在分析的所有组中均检测到粪便吲哚，但在AST-120给药组中未检测到粪便对甲酚。在属水平上，共有23种微生物因肾衰竭或AST-120治疗而发生显著变化。特别是，AST-120减少了未培养的丹毒丝菌科和狭义梭菌1的丰度，它们具有参与对甲酚生产的基因。我们的研究结果表明，除了尿毒症毒素前体的吸附外，AST-120还影响正常和肾衰竭条件下某些肠道微生物群的丰度，从而解释了对IS和pCS的不同衰减效应。(C)2020爱思唯尔公司All rights reserved.
In chronic kidney disease, elevated levels of circulating uremic toxins are associated with a variety of symptoms and organ dysfunction. Indoxyl sulfate (IS) and p-cresyl sulfate (pCS) are microbiota-derived metabolites and representative uremic toxins. We have previously shown that the oral adsorbent AST120 profoundly reduced pCS compared to IS in adenine-induced renal failure in mice. However, the mechanisms of the different attenuation effects of AST-120 between IS and pCS are unclear. To clarify the difference of AST-120 on IS and pCS, we investigated the levels of fecal indole and p-cresol, the respective precursors of IS and pCS, and examined the influence on the gut microbiota. Although fecal indole was detected in all groups analyzed, fecal p-cresol was not detected in AST-120 treatment groups. In genus level, a total of 23 organisms were significantly changed by renal failure or AST-120 treatment. Especially, AST-120 reduced the abundance of Erysipelotrichaceae uncultured and Clostridium sensu stricto 1, which have a gene involved in p-cresol production. Our findings suggest that, in addition to the adsorption of the uremic toxin precursors, AST-120 affects the abundance of some gut microbiota in normal and renal failure conditions, thereby explaining the different attenuation effects on IS and pCS. (C) 2020 Elsevier Inc. All rights reserved.