Species variation in the fecal metabolome gives insight into differential gastrointestinal function

被引:152
作者
Saric, Jasmina [1 ,2 ]
Wang, Yulan [1 ]
Li, Jia [1 ,2 ]
Coen, Muireann [1 ]
Utzinger, Juerg [2 ]
Marchesi, Julian R. [3 ]
Keiser, Jennifer [2 ]
Veselkov, Kirill [1 ]
Lindon, John C. [1 ]
Nicholson, Jeremy K. [1 ]
Holmes, Elaine [1 ]
机构
[1] Univ London Imperial Coll Sci Technol & Med, Fac Med, Div Surg Oncol Reproduct Biol & Anaesthet, Dept Biomol Med, London SW7 2AZ, England
[2] Swiss Trop Inst, Dept Publ Hlth, CH-4002 Basel, Switzerland
[3] Natl Univ Ireland Univ Coll Cork, Dept Microbiol, Cork, Ireland
关键词
fecal extracts; gut microbiota; H-1 NMR spectroscopy; multivariate statistical analysis; metabonomics; metabolomics; metabolite profiling;
D O I
10.1021/pr070340k
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
The metabolic composition of fecal extracts provides a window for elucidating the complex metabolic interplay between mammals and their intestinal ecosystems, and these metabolite profiles can yield information on a range of gut diseases. Here, the metabolites present in aqueous fecal extracts of humans, mice and rats were characterized using high-resolution H-1 NMR spectroscopy coupled with multivariate pattern recognition techniques. Additionally, the effects of sample storage and preparation methods were evaluated in order to assess the stability of fecal metabolite profiles, and to optimize information recovery from fecal samples. Finally, variations in metabolite profiles were investigated in healthy mice as a function of time. Interspecies variation was found to be greater than the variation due to either time or sample preparation. Although many fecal metabolites were common to the three species, such as short chain fatty acids and branched chain amino acids, each species generated a unique profile. Relatively higher levels of uracil, hypoxanthine, phenylacetic acid, glucose, glycine, and tyrosine amino acids were present in the rat, with beta-alanine being unique to the rat, and glycerol and malonate being unique to the human. Human fecal extracts showed a greater interindividual variation than the two rodent species, reflecting the natural genetic and environmental diversity in human populations. Fecal composition in healthy mice was found to change over time, which might be explained by altered gut microbial presence or activity. The systematic characterization of fecal composition across humans, mice, and rats, together with the evaluation of inherent variation, provides a benchmark for future studies seeking to determine fecal biomarkers of disease and/or response to dietary or therapeutic interventions.
引用
收藏
页码:352 / 360
页数:9
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