title: Top-down systems biology modeling of host metabotype-microbiome associations in obese rodents.
abstract: 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 (fa/-, n=8) and lean (-/-, n=8)) were characterized via high-resolution 1H 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 (fa/- 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.
authors.affiliation: Department of Biomolecular Medicine, SORA Division, Faculty of Medicine, Sir Alexander Fleming Building, Imperial College London, South Kensington SW7 2AZ, United Kingdom.
authors.forename: Alison
authors.initials: A
authors.lastname: Waldram
authors.forename: Elaine
authors.initials: E
authors.lastname: Holmes
authors.forename: Yulan
authors.initials: Y
authors.lastname: Wang
authors.forename: Mattias
authors.initials: M
authors.lastname: Rantalainen
authors.forename: Ian D
authors.initials: ID
authors.lastname: Wilson
authors.forename: Kieran M
authors.initials: KM
authors.lastname: Tuohy
authors.forename: Anne L
authors.initials: AL
authors.lastname: McCartney
authors.forename: Glenn R
authors.initials: GR
authors.lastname: Gibson
authors.forename: Jeremy K
authors.initials: JK
authors.lastname: Nicholson
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001419:Bacteria / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D001424:Bacterial Infections / Q000097:blood / Q000378:metabolism / Q000652:urine; D001644:Bifidobacterium / Q000235:genetics / Q000502:physiology; D001786:Blood Glucose / Q000032:analysis; D003013:Clostridium / Q000235:genetics / Q000502:physiology; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D005243:Feces / Q000382:microbiology; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D054884:Host-Pathogen Interactions; D007778:Lactobacillus / Q000235:genetics / Q000502:physiology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055432:Metabolomics / Q000379:methods; D023421:Models, Animal; D009765:Obesity / Q000378:metabolism* / Q000382:microbiology*; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D051381:Rats; D011924:Rats, Zucker; D017422:Sequence Analysis, DNA; D014556:Urine / Q000737:chemistry
chemical_list: D001786:Blood Glucose; D004269:DNA, Bacterial; D012336:RNA, Ribosomal, 16S