Metabonomic and Microbiological Analysis of the Dynamic Effect of Vancomycin-Induced Gut Microbiota Modification in the Mouse

• Published in: Journal of proteome research Vol. 7; no. 9; pp. 3718 - 3728
• Main Authors: Yap, Ivan K. S, Li, Jia V, Saric, Jasmina, Martin, Francois-Pierre, Davies, Huw, Wang, Yulan, Wilson, Ian D, Nicholson, Jeremy K, Utzinger, Jürg, Marchesi, Julian R, Holmes, Elaine
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01.09.2008
• Subjects: Animals; Anti-Bacterial Agents - pharmacology; Base Sequence; DNA Primers; Electrophoresis, Polyacrylamide Gel; Feces - chemistry; Female; Glycine - analogs & derivatives; Glycine - urine; Hippurates - urine; Intestines - microbiology; Mice; Nuclear Magnetic Resonance, Biomolecular; Polymerase Chain Reaction; RNA, Ribosomal, 16S - genetics; Urine; Vancomycin - pharmacology; Urine; Metabolomics; Co-metabolism; Microbiota; NMR; Pattern Recognition; Mouse; Metabonomics; Propionate; Feces; Vancomycin; Butyrate
• ISSN: 1535-3893; 1535-3907
• DOI: 10.1021/pr700864x

The effects of the antibiotic vancomycin (2 × 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 1H 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.