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PMID: 18854818 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Systemic multicompartmental effects of the gut microbiome on mouse metabolic phenotypes.

Molecular systems biology ·Vol. 4 ·2008-00-00 ·Pages 219

Claus SP, Tsang TM, Wang Y, Cloarec O, Skordi E, Martin FP, Rezzi S, Ross A, Kochhar S, Holmes E, Nicholson JK

Abstract

To characterize the impact of gut microbiota on host metabolism, we investigated the multicompartmental metabolic profiles of a conventional mouse strain (C3H/HeJ) (n=5) and its germ-free (GF) equivalent (n=5). We confirm that the microbiome strongly impacts on the metabolism of bile acids through the enterohepatic cycle and gut metabolism (higher levels of phosphocholine and glycine in GF liver and marked higher levels of bile acids in three gut compartments). Furthermore we demonstrate that (1) well-defined metabolic differences exist in all examined compartments between the metabotypes of GF and conventional mice: bacterial co-metabolic products such as hippurate (urine) and 5-aminovalerate (colon epithelium) were found at reduced concentrations, whereas raffinose was only detected in GF colonic profiles. (2) The microbiome also influences kidney homeostasis with elevated levels of key cell volume regulators (betaine, choline, myo-inositol and so on) observed in GF kidneys. (3) Gut microbiota modulate metabotype expression at both local (gut) and global (biofluids, kidney, liver) system levels and hence influence the responses to a variety of dietary modulation and drug exposures relevant to personalized health-care investigations.

MeSH Terms
Amino Acids, Neutral/analysis Animals Bile Acids and Salts/metabolism Gastrointestinal Tract/metabolism,microbiology Hippurates/urine Kidney/metabolism Liver/metabolism Metabolism Metagenome Mice Mice, Inbred Strains Phenotype
Chemicals
Amino Acids, Neutral Bile Acids and Salts Hippurates 5-aminovaleric acid hippuric acid
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Claus Sandrine P
SORA Division, Department of Biomolecular Medicine, Imperial College London, London, UK.
Tsang Tsz M
Wang Yulan
Cloarec Olivier
Skordi Eleni
Martin François-Pierre
Rezzi Serge
Ross Alastair
Kochhar Sunil
Holmes Elaine
Nicholson Jeremy K
References (88)
88 references, click to expand
  1. Adaptation of bacteria to the intestinal niche: probiotics and gut disorder.
    Inflamm Bowel Dis. 2001 May;7(2):136-45 PMID: 11383587
  2. Endogenous glutathione conjugates: occurrence and biological functions.
    Pharmacol Rev. 1998 Sep;50(3):335-56 PMID: 9755286
  3. Mechanisms underlying the resistance to diet-induced obesity in germ-free mice.
    Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):979-84 PMID: 17210919
  4. The intestine and its microflora are partners for the protection of the host: report on the Danone Symposium "The Intelligent Intestine," held in Paris, June 14, 2002.
    Am J Clin Nutr. 2003 Oct;78(4):675-83 PMID: 14522724
  5. Metabolic profiling reveals a contribution of gut microbiota to fatty liver phenotype in insulin-resistant mice.
    Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12511-6 PMID: 16895997
  6. The indigenous gastrointestinal microflora.
    Trends Microbiol. 1996 Nov;4(11):430-5 PMID: 8950812
  7. The gut microbiota as an environmental factor that regulates fat storage.
    Proc Natl Acad Sci U S A. 2004 Nov 2;101(44):15718-23 PMID: 15505215
  8. Global systems biology, personalized medicine and molecular epidemiology.
    Mol Syst Biol. 2006;2:52 PMID: 17016518
  9. Metabonomics: a platform for studying drug toxicity and gene function.
    Nat Rev Drug Discov. 2002 Feb;1(2):153-61 PMID: 12120097
  10. The physiological consequences of glutathione variations.
    Life Sci. 1992;51(14):1083-94 PMID: 1518371
  11. Glutathione metabolism and its role in hepatotoxicity.
    Pharmacol Ther. 1991 Dec;52(3):287-305 PMID: 1820580
  12. Identification of a nuclear receptor for bile acids.
    Science. 1999 May 21;284(5418):1362-5 PMID: 10334992
  13. Endocrine functions of bile acids.
    EMBO J. 2006 Apr 5;25(7):1419-25 PMID: 16541101
  14. A combined (1)H NMR and HPLC-MS-based metabonomic study of urine from obese (fa/fa) Zucker and normal Wistar-derived rats.
    J Pharm Biomed Anal. 2005 Jul 1;38(3):465-71 PMID: 15925248
  15. Metabonomics technologies and their applications in physiological monitoring, drug safety assessment and disease diagnosis.
    Biomarkers. 2004 Jan-Feb;9(1):1-31 PMID: 15204308
  16. Strict host-symbiont cospeciation and reductive genome evolution in insect gut bacteria.
    PLoS Biol. 2006 Oct;4(10):e337 PMID: 17032065
  17. Contribution of microbial amino acids to amino acid homeostasis of the host.
    J Nutr. 2000 Jul;130(7):1857S-64S PMID: 10867063
  18. Biochemical characterization of rat intestine development using high-resolution magic-angle-spinning 1H NMR spectroscopy and multivariate data analysis.
    J Proteome Res. 2005 Jul-Aug;4(4):1324-9 PMID: 16083283
  19. Molecular basis of osmotic regulation.
    Am J Physiol. 1995 Jun;268(6 Pt 2):F983-96 PMID: 7611465
  20. Cell volume regulation: osmolytes, osmolyte transport, and signal transduction.
    Rev Physiol Biochem Pharmacol. 2003;148:1-80 PMID: 12687402
  21. Nutritional metabonomics: applications and perspectives.
    J Proteome Res. 2007 Feb;6(2):513-25 PMID: 17269708
  22. An obesity-associated gut microbiome with increased capacity for energy harvest.
    Nature. 2006 Dec 21;444(7122):1027-31 PMID: 17183312
  23. Amino acid degradation by anaerobic bacteria.
    Annu Rev Biochem. 1981;50:23-40 PMID: 6791576
  24. Metabolic capacity for L-citrulline synthesis from ammonia in rat isolated colonocytes.
    Biochim Biophys Acta. 1999 May 24;1427(3):401-7 PMID: 10350656
  25. Hypertonicity-induced accumulation of organic osmolytes in papillary interstitial cells.
    Kidney Int. 1999 Apr;55(4):1417-25 PMID: 10201006
  26. Metabonomic evaluation of Schaedler altered microflora rats.
    Chem Res Toxicol. 2007 Oct;20(10):1388-92 PMID: 17900170
  27. Structure of the intestinal flora responsible for development of the gut immune system in a rodent model.
    Microbes Infect. 2000 Sep;2(11):1343-51 PMID: 11018451
  28. NMR and pattern recognition studies on liver extracts and intact livers from rats treated with alpha-naphthylisothiocyanate.
    Biochem Pharmacol. 2002 Jul 1;64(1):67-77 PMID: 12106607
  29. Enzymatic reactions in the degradation of 5-aminovalerate by Clostridium aminovalericum.
    J Biol Chem. 1987 Jul 5;262(19):8994-9003 PMID: 3597403
  30. How host-microbial interactions shape the nutrient environment of the mammalian intestine.
    Annu Rev Nutr. 2002;22:283-307 PMID: 12055347
  31. Reduction of non-digestible oligosaccharides in soymilk: application of engineered lactic acid bacteria that produce alpha-galactosidase.
    Genet Mol Res. 2004;3(3):432-40 PMID: 15614733
  32. Regulation of cellular glutathione.
    Am J Physiol. 1989 Oct;257(4 Pt 1):L163-73 PMID: 2572174
  33. The germfree animal in nutritional studies.
    Annu Rev Nutr. 1981;1:257-79 PMID: 6764717
  34. Metabonomic identification of two distinct phenotypes in Sprague-Dawley (Crl:CD(SD)) rats.
    Toxicol Sci. 2005 Sep;87(1):277-84 PMID: 15933226
  35. NMR spectroscopic-based metabonomic studies of urinary metabolite variation in acclimatizing germ-free rats.
    Chem Res Toxicol. 2003 Nov;16(11):1395-404 PMID: 14615964
  36. Synthesis of Vitamins by Intestinal Bacteria.
    Proc Natl Acad Sci U S A. 1942 Jul;28(7):285-9 PMID: 16578052
  37. The antioxidant action of taurine, hypotaurine and their metabolic precursors.
    Biochem J. 1988 Nov 15;256(1):251-5 PMID: 2851980
  38. The Farnesoid X receptor: a molecular link between bile acid and lipid and glucose metabolism.
    Arterioscler Thromb Vasc Biol. 2005 Oct;25(10):2020-30 PMID: 16037564
  39. Quantitative and qualitative characterization of 1H NMR spectra of colon tumors, normal mucosa and their perchloric acid extracts: decreased levels of myo-inositol in tumours can be detected in intact biopsies.
    NMR Biomed. 1996 Feb;9(1):33-45 PMID: 8842031
  40. Endotoxin from various gram-negative bacteria has differential effects on function of hepatic cytochrome P450 and drug transporters.
    Eur J Pharmacol. 2005 Mar 7;510(1-2):127-34 PMID: 15740733
  41. Distinct signals from the microbiota promote different aspects of zebrafish gut differentiation.
    Dev Biol. 2006 Sep 15;297(2):374-86 PMID: 16781702
  42. Effects of cholic acid, chenodeoxycholic acid, and their related bile acids on cholesterol, phospholipid, and bile acid levels in serum, liver, bile, and feces of rats.
    J Biochem. 1980 Jan;87(1):187-94 PMID: 7358627
  43. Metabolism and excretion of methylamines in rats.
    Toxicol Appl Pharmacol. 1994 Apr;125(2):296-308 PMID: 8171437
  44. Gut flora and the origin of some urinary aromatic phenolic compounds.
    Biochem Pharmacol. 1994 Jun 15;47(12):2294-7 PMID: 8031324
  45. Glutathione metabolism and its selective modification.
    J Biol Chem. 1988 Nov 25;263(33):17205-8 PMID: 3053703
  46. Myo-inositol and betaine transporters regulated by tonicity are basolateral in MDCK cells.
    Am J Physiol. 1991 Jul;261(1 Pt 2):F197-202 PMID: 1858900
  47. Commensal host-bacterial relationships in the gut.
    Science. 2001 May 11;292(5519):1115-8 PMID: 11352068
  48. Pharmaco-metabonomic phenotyping and personalized drug treatment.
    Nature. 2006 Apr 20;440(7087):1073-7 PMID: 16625200
  49. Gut microorganisms, mammalian metabolism and personalized health care.
    Nat Rev Microbiol. 2005 May;3(5):431-8 PMID: 15821725
  50. Ablation of the Tamm-Horsfall protein gene increases susceptibility of mice to bladder colonization by type 1-fimbriated Escherichia coli.
    Am J Physiol Renal Physiol. 2004 Apr;286(4):F795-802 PMID: 14665435
  51. Directed TOCSY, a method for selection of directed correlations by optimal combinations of isotropic and longitudinal mixing.
    J Magn Reson B. 1996 Aug;112(2):160-80 PMID: 8812900
  52. Tamm-Horsfall glycoprotein: biology and clinical relevance.
    Am J Kidney Dis. 2003 Oct;42(4):658-76 PMID: 14520616
  53. Variation in gut microbiota strongly influences individual rodent phenotypes.
    Toxicol Sci. 2005 Sep;87(1):1-2 PMID: 16158497
  54. Glutathione and related gamma-glutamyl compounds: biosynthesis and utilization.
    Annu Rev Biochem. 1976;45:559-604 PMID: 9027
  55. NMR-based metabonomic approaches for evaluating physiological influences on biofluid composition.
    NMR Biomed. 2005 May;18(3):143-62 PMID: 15627238
  56. The enzymes, regulation, and genetics of bile acid synthesis.
    Annu Rev Biochem. 2003;72:137-74 PMID: 12543708
  57. Effect of intestinal microflora on the urinary metabolic profile of rats: a (1)H-nuclear magnetic resonance spectroscopy study.
    Xenobiotica. 2002 Sep;32(9):783-94 PMID: 12396275
  58. Nuclear bile acid receptor FXR as pharmacological target: are we there yet?
    FEBS Lett. 2006 Oct 9;580(23):5492-9 PMID: 16904670
  59. Transgenomic metabolic interactions in a mouse disease model: interactions of Trichinella spiralis infection with dietary Lactobacillus paracasei supplementation.
    J Proteome Res. 2006 Sep;5(9):2185-93 PMID: 16944930
  60. Microbial ecology: human gut microbes associated with obesity.
    Nature. 2006 Dec 21;444(7122):1022-3 PMID: 17183309
  61. Tamm-Horsfall protein binds to type 1 fimbriated Escherichia coli and prevents E. coli from binding to uroplakin Ia and Ib receptors.
    J Biol Chem. 2001 Mar 30;276(13):9924-30 PMID: 11134021
  62. Polyphenols: food sources and bioavailability.
    Am J Clin Nutr. 2004 May;79(5):727-47 PMID: 15113710
  63. Host-bacterial mutualism in the human intestine.
    Science. 2005 Mar 25;307(5717):1915-20 PMID: 15790844
  64. A glance at G-protein-coupled receptors for lipid mediators: a growing receptor family with remarkably diverse ligands.
    Pharmacol Ther. 2004 Jun;102(3):243-57 PMID: 15246248
  65. Aryl hydrocarbon receptor regulates distinct dioxin-dependent and dioxin-independent gene batteries.
    Mol Pharmacol. 2006 Jan;69(1):140-53 PMID: 16214954
  66. An NMR-based metabonomic approach to investigate the biochemical consequences of genetic strain differences: application to the C57BL10J and Alpk:ApfCD mouse.
    FEBS Lett. 2000 Nov 10;484(3):169-74 PMID: 11078872
  67. A top-down systems biology view of microbiome-mammalian metabolic interactions in a mouse model.
    Mol Syst Biol. 2007;3:112 PMID: 17515922
  68. Host-bacterial interactions in Helicobacter pylori infection.
    Gastroenterology. 2008 Jan;134(1):306-23 PMID: 18166359
  69. A G protein-coupled receptor responsive to bile acids.
    J Biol Chem. 2003 Mar 14;278(11):9435-40 PMID: 12524422
  70. Evaluation of the orthogonal projection on latent structure model limitations caused by chemical shift variability and improved visualization of biomarker changes in 1H NMR spectroscopic metabonomic studies.
    Anal Chem. 2005 Jan 15;77(2):517-26 PMID: 15649048
  71. 750 MHz 1H and 1H-13C NMR spectroscopy of human blood plasma.
    Anal Chem. 1995 Mar 1;67(5):793-811 PMID: 7762816
  72. The continuing importance of bile acids in liver and intestinal disease.
    Arch Intern Med. 1999 Dec 13-27;159(22):2647-58 PMID: 10597755
  73. Functional activity of the mouse flavin-containing monooxygenase forms 1, 3, and 5.
    J Biochem Mol Toxicol. 2007;21(4):206-15 PMID: 17721934
  74. Glutathione.
    Annu Rev Biochem. 1983;52:711-60 PMID: 6137189
  75. Hyperosmotic stress response: comparison with other cellular stresses.
    Pflugers Arch. 2007 May;454(2):173-85 PMID: 17206446
  76. Phytoestrogens: the biochemistry, physiology, and implications for human health of soy isoflavones.
    Am J Clin Nutr. 1998 Dec;68(6 Suppl):1333S-1346S PMID: 9848496
  77. Metabolic characterization of the R6/2 transgenic mouse model of Huntington's disease by high-resolution MAS 1H NMR spectroscopy.
    J Proteome Res. 2006 Mar;5(3):483-92 PMID: 16512662
  78. Cellular response to osmotic stress in the renal medulla.
    Pflugers Arch. 1998 Nov;436(6):814-27 PMID: 9799394
  79. Assessment of analytical reproducibility of 1H NMR spectroscopy based metabonomics for large-scale epidemiological research: the INTERMAP Study.
    Anal Chem. 2006 Apr 1;78(7):2199-208 PMID: 16579598
  80. Organic osmolytes as compatible, metabolic and counteracting cytoprotectants in high osmolarity and other stresses.
    J Exp Biol. 2005 Aug;208(Pt 15):2819-30 PMID: 16043587
  81. S-[2-(N7-guanyl)ethyl]glutathione, the major DNA adduct formed from 1,2-dibromoethane.
    Biochemistry. 1986 Apr 22;25(8):2192-8 PMID: 3707941
  82. Gut bacterial metabolism of the soy isoflavone daidzein: exploring the relevance to human health.
    Exp Biol Med (Maywood). 2005 Mar;230(3):155-70 PMID: 15734719
  83. High-resolution (1)H NMR and magic angle spinning NMR spectroscopic investigation of the biochemical effects of 2-bromoethanamine in intact renal and hepatic tissue.
    Magn Reson Med. 2001 May;45(5):781-90 PMID: 11323804
  84. Relationships between bile salts hydrophilicity and phospholipid composition in bile of various animal species.
    Comp Biochem Physiol B. 1986;83(3):551-4 PMID: 3956167
  85. Scyllo-inositol depletion in hepatic encephalopathy.
    Life Sci. 1994;54(20):1507-12 PMID: 8190025
  86. Gastrointestinal microflora in mammalian nutrition.
    Annu Rev Nutr. 1986;6:155-78 PMID: 3524615
  87. Topographical variation in metabolic signatures of human gastrointestinal biopsies revealed by high-resolution magic-angle spinning 1H NMR spectroscopy.
    J Proteome Res. 2007 Oct;6(10):3944-51 PMID: 17711324
  88. Hepatic encephalopathy: molecular mechanisms underlying the clinical syndrome.
    J Neurol Sci. 1999 Nov 30;170(2):138-46 PMID: 10617392
Article Info
Journal
Molecular systems biology
Abbr.
Mol Syst Biol
ISSN
1744-4292
DOI
10.1038/msb.2008.56
Published
2008-00-00
Epub
2008-00-14
Pages
219
Language
English
Region
England
NLM ID
101235389
PMCID
PMC2583082
Subset
IM
External Links
PubMed source DOI: 10.1038/msb.2008.56 PMC Full Text View journal details
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