Metabonomic and microbiological analysis of the dynamic effect of vancomycin-induced gut microbiota modification in the mouse.
Metabonomic and microbiological analysis of the dynamic effect of vancomycin-induced gut microbiota modification in the mouse.
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DOI：
10.1021/pr700864x
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发表时间：
2008-08
影响因子：
4.4
通讯作者：
I. Yap;Jia V. Li;J. Saric;F. Martin;Huw Davies;Yulan Wang;I. Wilson;J. Nicholson;J. Utzinger;J. Marchesi;E. Holmes
中科院分区：
文献类型：
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作者：
I. Yap;Jia V. Li;J. Saric;F. Martin;Huw Davies;Yulan Wang;I. Wilson;J. Nicholson;J. Utzinger;J. Marchesi;E. Holmes
研究了抗生素万古霉素（2 x 100 mg/kg/天）对雌性小鼠（远交NMRI品系）肠道微生物群的影响，以评估肠道微生物群对宿主代谢的相对贡献。使用尿液和粪便提取物样品的（1）H NMR光谱表征宿主的代谢表型。使用16S rRNA基因PCR和变性梯度凝胶电泳（PCR-DGGE）分析监测万古霉素给药后肠道微生物群落的时程变化，结果显示对几个物种（主要是厚壁菌门）有强烈影响。万古霉素治疗与尿嘧啶、氨基酸和短链脂肪酸（SCFA）的粪便排泄相关，突出了肠道微生物群对这些膳食化合物的产生和代谢的贡献。在本研究中观察到对照组和驱虫组小鼠之间肠道微生物群落的明显差异。还观察到肠道微生物共代谢物苯乙酰甘氨酸和马尿酸盐的尿排泄减少。尿马尿酸和苯乙酰甘氨酸浓度对粪便代谢产物谱的回归显示，这些尿代谢产物与各种粪便代谢产物（包括氨基酸和SCFA）之间存在强相关性。粪便胆碱与尿马尿酸呈负相关。代谢谱分析，再加上宏基因组研究的抗生素模型，说明了宿主和微生物的“代谢型”之间的密切关系，并将提供进一步的实验探索微生物哺乳动物代谢轴的理解的基础。
The effects of the antibiotic vancomycin (2 x 100 mg/kg/day) on the gut microbiota of female mice (outbred NMRI strain) were studied, in order to assess the relative contribution of the gut microbiome to host metabolism. The host's metabolic phenotype was characterized using (1)H NMR spectroscopy of urine and fecal extract samples. Time-course changes in the gut microbiotal community after administration of vancomycin were monitored using 16S rRNA gene PCR and denaturing gradient gel electrophoresis (PCR-DGGE) analysis and showed a strong effect on several species, mostly within the Firmicutes. Vancomycin treatment was associated with fecal excretion of uracil, amino acids and short chain fatty acids (SCFAs), highlighting the contribution of the gut microbiota to the production and metabolism of these dietary compounds. Clear differences in gut microbial communities between control and antibiotic-treated mice were observed in the current study. Reduced urinary excretion of gut microbial co-metabolites phenylacetylglycine and hippurate was also observed. Regression of urinary hippurate and phenylacetylglycine concentrations against the fecal metabolite profile showed a strong association between these urinary metabolites and a wide range of fecal metabolites, including amino acids and SCFAs. Fecal choline was inversely correlated with urinary hippurate. Metabolic profiling, coupled with the metagenomic study of this antibiotic model, illustrates the close inter-relationship between the host and microbial "metabotypes", and will provide a basis for further experiments probing the understanding of the microbial-mammalian metabolic axis.