Expansion of urease- and uricase-containing, indole- and p-cresol-forming and contraction of short-chain fatty acid-producing intestinal microbiota in ESRD.
Expansion of urease- and uricase-containing, indole- and p-cresol-forming and contraction of short-chain fatty acid-producing intestinal microbiota in ESRD.
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DOI：
10.1159/000360010
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发表时间：
2014
影响因子：
4.2
通讯作者：
Vaziri ND
中科院分区：
文献类型：
--
作者：
Wong J;Piceno YM;DeSantis TZ;Pahl M;Andersen GL;Vaziri ND
肠道微生物群构成了一个对健康至关重要的共生生态系统，其组成/功能的变化会导致各种疾病。生化环境塑造了微生物组的结构和功能。最近，我们发现ESRD患者和健康人在许多细菌类群的丰度上有显著差异。尿素、尿酸内流及限制果蔬饮食预防高血钾改变ESRD患者肠道环境。我们推测，在ESRD中，具有尿素酶、尿酸酶、对甲酚和吲哚产生酶的细菌的相对丰度增加，而含有将膳食纤维转化为短链脂肪酸(SCFA)的酶的细菌的丰度降低。将含有感兴趣基因的细菌参考集汇编成家族，并汇编了在我们最初研究中登记的12名健康个体和24名ESRD个体之间存在差异的肠道细菌家族。使用超几何分布检验评估集合之间的重叠。在ESRD患者的19个优势菌系中，12个具有尿素酶，5个具有尿酸酶，4个具有吲哚和对甲酚形成酶。在ESRD患者缺失的4个微生物家族中，有2个具有丁酸形成酶。这些重叠分布的概率为<；0.05。ESRD患者具有尿素酶、尿酸酶、吲哚和对甲酚形成酶的细菌家族显著扩大，而具有丁酸形成酶的细菌家族显著收缩。鉴于吲哚硫酸盐、对甲酚硫酸盐和尿素衍生的氨的有害作用，以及SCFA的有益作用，这些肠道微生物代谢的变化导致尿毒症毒性和炎症。
Intestinal microbiome constitutes a symbiotic ecosystem that is essential for health, and changes in its composition/function cause various illnesses. Biochemical milieu shapes the structure and function of the microbiome. Recently we found marked differences in the abundance of numerous bacterial taxa between ESRD and healthy individuals. Influx of urea and uric acid and dietary restriction of fruits and vegetables to prevent hyperkalemia alter ESRD patients’ intestinal milieu. We hypothesized that relative abundances of bacteria possessing urease, uricase, and p-cresol- and indole-producing enzymes is increased, while abundance of bacteria containing enzymes converting dietary fiber to short chain fatty acids (SCFA) is reduced in ESRD. Reference sets of bacteria containing genes of interest were compiled to family, and sets of intestinal bacterial families showing differential abundances between 12 healthy and 24 ESRD individuals enrolled in our original study were compiled. Overlap between sets was assessed using hypergeometric distribution tests. : Among 19 microbial families that were dominant in ESRD patients, 12 possessed urease, 5 possessed uricase, and 4 possessed indole and p-cresol forming enzymes. Among 4 microbial families that were diminished in ESRD patients, 2 possessed butyrate-forming enzymes. Probabilities of these overlapping distributions were <0.05. ESRD patients exhibited significant expansion of bacterial families possessing urease, uricase, and indole and p-cresol forming enzymes, and contraction of families possessing butyrate-forming enzymes. Given the deleterious effects of indoxyl sulfate, p-cresol sulfate, and urea-derived ammonia, and beneficial actions of SCFA, these changes in intestinal microbial metabolism contribute to uremic toxicity and inflammation.
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影响因子：
29
作者：
Donohoe DR;Garge N;Zhang X;Sun W;O'Connell TM;Bunger MK;Bultman SJ
通讯作者：
Bultman SJ
影响因子：
3.7
作者：
Nacke H;Thürmer A;Wollherr A;Will C;Hodac L;Herold N;Schöning I;Schrumpf M;Daniel R
通讯作者：
Daniel R
影响因子：
6.1
作者：
Hendrikx, Thijs K.;van Gurp, Eveline A. F. J.;Baan, Carla C.
通讯作者：
Baan, Carla C.
影响因子：
2.5
作者：
Lee, Y T
通讯作者：
Lee, Y T
影响因子：
13.6
作者：
Aronov, Pavel A.;Luo, Frank J. -G.;Meyer, Timothy W.
通讯作者：
Meyer, Timothy W.