Microbiome-metabolomics reveals gut microbiota associated with glycine-conjugated metabolites and polyamine metabolism in chronic kidney disease
Microbiome-metabolomics reveals gut microbiota associated with glycine-conjugated metabolites and polyamine metabolism in chronic kidney disease
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微生物组代谢组学揭示了慢性肾病中与甘氨酸结合代谢物和多胺代谢相关的肠道微生物群
DOI：
10.1007/s00018-019-03155-9
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发表时间：
2019-12-01
影响因子：
8
通讯作者：
Zhao, Ying-Yong
中科院分区：
文献类型：
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作者：
Feng, Ya-Long;Cao, Gang;Zhao, Ying-Yong
慢性肾脏疾病（CKD）中肠道微生物组和相关代谢物的生态失调与心血管疾病的患病率密切相关。不幸的是，到目前为止，对肠道微生物组和相关代谢物对CKD进展的了解还不够，部分原因是研究非常有限。使用5/6肾切除（NX）大鼠模型，我们进行了16 S rRNA序列和非靶向代谢组学分析，以探讨结肠微生物群与血清代谢物之间的关系。微生物多样性和丰富度的显著下降伴随着291种血清代谢物的显著变化，这是由酶活性改变和脂质、氨基酸、胆汁酸和多胺代谢的失调介导的。有趣的是，CCr与一些微生物属和多胺代谢直接相关。然而，SBP与CKD大鼠中的某些微生物属和甘氨酸结合代谢物直接相关。给予茯苓酸A（PAA）和茯苓（PC）可改善微生物生态失调，并减轻高血压和肾纤维化。此外，PAA和PC的治疗降低了血清中微生物衍生产物的水平，包括甘氨酸共轭化合物和多胺代谢产物。总的来说，本研究证实了CKD相关的肠道微生物生态失调，并确定了一种新的饮食和治疗策略，以改善肠道微生物生态失调和相关的代谢组学紊乱，并延缓CKD大鼠模型中肾脏疾病的进展。
Dysbiosis of the gut microbiome and related metabolites in chronic kidney disease (CKD) have been intimately associated with the prevalence of cardiovascular diseases. Unfortunately, thus far, there is a paucity of sufficient knowledge of gut microbiome and related metabolites on CKD progression partly due to the severely limited investigations. Using a 5/6 nephrectomized (NX) rat model, we carried out 16S rRNA sequence and untargeted metabolomic analyses to explore the relationship between colon's microbiota and serum metabolites. Marked decline in microbial diversity and richness was accompanied by significant changes in 291 serum metabolites, which were mediated by altered enzymatic activities and dysregulations of lipids, amino acids, bile acids and polyamines metabolisms. Interestingly, CCr was directly associated with some microbial genera and polyamine metabolism. However, SBP was directly related to certain microbial genera and glycine-conjugated metabolites in CKD rats. Administration of poricoic acid A (PAA) and Poria cocos (PC) ameliorated microbial dysbiosis as well as attenuated hypertension and renal fibrosis. In addition, treatments with PAA and PC lowered serum levels of microbial-derived products including glycine-conjugated compounds and polyamine metabolites. Collectively, the present study confirmed the CKD-associated gut microbial dysbiosis and identified a novel dietary and therapeutic strategy to improve the gut microbial dysbiosis and the associated metabolomic disorders and retarded the progression of kidney disease in the rat model of CKD.