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Top-down systems biology modeling of host metabotype-microbiome associations in obese rodents

Waldram, A., Holmes, E., Wang, Y.L., Rantalainen, M., Wilson, I.D., Tuohy, K.M., McCartney, A.L., Gibson, G.R. and Nicholson, J.K. (2009) Top-down systems biology modeling of host metabotype-microbiome associations in obese rodents. Journal of Proteome Research, 8 (5). pp. 2361-2375. ISSN 1535-3893

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To link to this article DOI: 10.1021/pr8009885

Abstract/Summary

Covariation in the structural composition of the gut microbiome and the spectroscopically derived metabolic phenotype (metabotype) of a rodent model for obesity were investigated using a range of multivariate statistical tools. Urine and plasma samples from three strains of 10-week-old male Zucker rats (obese (fa/fa, n = 8), lean (fal-, n = 8) and lean (-/-, n = 8)) were characterized via high-resolution H-1 NMR spectroscopy, and in parallel, the fecal microbial composition was investigated using fluorescence in situ hydridization (FISH) and denaturing gradient gel electrophoresis (DGGE) methods. All three Zucker strains had different relative abundances of the dominant members of their intestinal microbiota (FISH), with the novel observation of a Halomonas and a Sphingomonas species being present in the (fa/fa) obese strain on the basis of DGGE data. The two functionally and phenotypically normal Zucker strains (fal- and -/-) were readily distinguished from the (fa/fa) obese rats on the basis of their metabotypes with relatively lower urinary hippurate and creatinine, relatively higher levels of urinary isoleucine, leucine and acetate and higher plasma LDL and VLDL levels typifying the (fa/fa) obese strain. Collectively, these data suggest a conditional host genetic involvement in selection of the microbial species in each host strain, and that both lean and obese animals could have specific metabolic phenotypes that are linked to their individual microbiomes.

Item Type:Article
Refereed:Yes
Divisions:Faculty of Life Sciences > School of Chemistry, Food and Pharmacy > Department of Food and Nutritional Sciences > Food Microbial Sciences Research Group
ID Code:12876
Uncontrolled Keywords:Zucker rat, FISH, metabonomics, metabotype, microbiota, obesity, OPLS-DA, O2PLS, H-1 NMR, metagenomics , 16S RIBOSOMAL-RNA, GRADIENT GEL-ELECTROPHORESIS, IN-SITU HYBRIDIZATION, HUMAN METABOLIC PHENOTYPES, METABONOMIC INVESTIGATIONS, OLIGONUCLEOTIDE PROBES, H-1-NMR SPECTROSCOPY, BACTERIAL DIVERSITY, MAGNETIC-RESONANCE, NMR-SPECTROSCOPY

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