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PMID: 21392406 Published · epublish English Journal Article

Gut microbiome-host interactions in health and disease.

Genome medicine ·Vol. 3 ·No. 3 ·2011-03-04 ·Pages 14

Kinross JM, Darzi AW, Nicholson JK

Abstract

The gut microbiome is the term given to describe the vast collection of symbiotic microorganisms in the human gastrointestinal system and their collective interacting genomes. Recent studies have suggested that the gut microbiome performs numerous important biochemical functions for the host, and disorders of the microbiome are associated with many and diverse human disease processes. Systems biology approaches based on next generation 'omics' technologies are now able to describe the gut microbiome at a detailed genetic and functional (transcriptomic, proteomic and metabolic) level, providing new insights into the importance of the gut microbiome in human health, and they are able to map microbiome variability between species, individuals and populations. This has established the importance of the gut microbiome in the disease pathogenesis for numerous systemic disease states, such as obesity and cardiovascular disease, and in intestinal conditions, such as inflammatory bowel disease. Thus, understanding microbiome activity is essential to the development of future personalized strategies of healthcare, as well as potentially providing new targets for drug development. Here, we review recent metagenomic and metabonomic approaches that have enabled advances in understanding gut microbiome activity in relation to human health, and gut microbial modulation for the treatment of disease. We also describe possible avenues of research in this rapidly growing field with respect to future personalized healthcare strategies.

Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Kinross James M
Section of Bimolecular Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, The Sir Alexander Fleming Building, South Kensington, London SW7 2AZ, UK. [email protected].
Darzi Ara W
Nicholson Jeremy K
References (99)
99 references, click to expand
  1. Characterization of the oral fungal microbiome (mycobiome) in healthy individuals.
    PLoS Pathog. 2010 Jan 08;6(1):e1000713 PMID: 20072605
  2. Metagenomics: genomic analysis of microbial communities.
    Annu Rev Genet. 2004;38:525-52 PMID: 15568985
  3. Medically important bacterial-fungal interactions.
    Nat Rev Microbiol. 2010 May;8(5):340-9 PMID: 20348933
  4. Influence of diets containing high and low risk factors for colon cancer on early stages of carcinogenesis in human flora-associated (HFA) rats.
    Carcinogenesis. 1997 Aug;18(8):1535-9 PMID: 9276627
  5. Selection of bacteria originating from a human intestinal microbiota in the gut of previously germ-free rats.
    FEMS Microbiol Lett. 2007 Dec;277(2):205-9 PMID: 18031341
  6. Infectious history.
    Science. 2000 Apr 14;288(5464):287-93 PMID: 10777411
  7. Bioecologic control of the gastrointestinal tract: the role of flora and supplemented probiotics and synbiotics.
    Gastroenterol Clin North Am. 2005 Sep;34(3):413-36, viii PMID: 16084305
  8. Commensal host-bacterial relationships in the gut.
    Science. 2001 May 11;292(5519):1115-8 PMID: 11352068
  9. Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5.
    Science. 2010 Apr 9;328(5975):228-31 PMID: 20203013
  10. Maturation of the murine cecal microbiota as revealed by terminal restriction fragment length polymorphism and 16S rRNA gene clone libraries.
    FEMS Microbiol Lett. 2004 Jun 1;235(1):139-46 PMID: 15158273
  11. The gastrointestinal microbiota as a site for the biotransformation of drugs.
    Int J Pharm. 2008 Nov 3;363(1-2):1-25 PMID: 18682282
  12. An ecological and evolutionary perspective on human-microbe mutualism and disease.
    Nature. 2007 Oct 18;449(7164):811-8 PMID: 17943117
  13. Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites.
    Proc Natl Acad Sci U S A. 2009 Mar 10;106(10):3698-703 PMID: 19234110
  14. Real-time PCR quantitation of clostridia in feces of autistic children.
    Appl Environ Microbiol. 2004 Nov;70(11):6459-65 PMID: 15528506
  15. Probiotic modulation of symbiotic gut microbial-host metabolic interactions in a humanized microbiome mouse model.
    Mol Syst Biol. 2008;4:157 PMID: 18197175
  16. An obesity-associated gut microbiome with increased capacity for energy harvest.
    Nature. 2006 Dec 21;444(7122):1027-31 PMID: 17183312
  17. Metabonomics: a platform for studying drug toxicity and gene function.
    Nat Rev Drug Discov. 2002 Feb;1(2):153-61 PMID: 12120097
  18. Human metabolic phenotype diversity and its association with diet and blood pressure.
    Nature. 2008 May 15;453(7193):396-400 PMID: 18425110
  19. The gut microbiota predispose to the pathophysiology of acute postradiotherapy diarrhea.
    Am J Gastroenterol. 2008 Jul;103(7):1754-61 PMID: 18564125
  20. Metagenomics: DNA sequencing of environmental samples.
    Nat Rev Genet. 2005 Nov;6(11):805-14 PMID: 16304596
  21. Changes in the composition of the human fecal microbiome after bacteriotherapy for recurrent Clostridium difficile-associated diarrhea.
    J Clin Gastroenterol. 2010 May-Jun;44(5):354-60 PMID: 20048681
  22. Long-term stability of the human gut microbiota in two different rat strains.
    Curr Issues Mol Biol. 2008;10(1-2):17-24 PMID: 18525103
  23. The re-emerging role of the intestinal microflora in critical illness and inflammation: why the gut hypothesis of sepsis syndrome will not go away.
    J Leukoc Biol. 2008 Mar;83(3):461-6 PMID: 18160538
  24. Symbiotic gut microbes modulate human metabolic phenotypes.
    Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):2117-22 PMID: 18252821
  25. Species variation in the fecal metabolome gives insight into differential gastrointestinal function.
    J Proteome Res. 2008 Jan;7(1):352-60 PMID: 18052033
  26. Top-down systems biology modeling of host metabotype-microbiome associations in obese rodents.
    J Proteome Res. 2009 May;8(5):2361-75 PMID: 19275195
  27. Top-down systems biology integration of conditional prebiotic modulated transgenomic interactions in a humanized microbiome mouse model.
    Mol Syst Biol. 2008;4:205 PMID: 18628745
  28. "Flora Power"-- fecal bacteria cure chronic C. difficile diarrhea.
    Am J Gastroenterol. 2000 Nov;95(11):3028-9 PMID: 11095314
  29. Development of the human infant intestinal microbiota.
    PLoS Biol. 2007 Jul;5(7):e177 PMID: 17594176
  30. The importance of the development of the intestinal microbiota in infancy.
    Curr Opin Pediatr. 2009 Dec;21(6):794-800 PMID: 19770768
  31. The human microbiome: eliminating the biomedical/environmental dichotomy in microbial ecology.
    Environ Microbiol. 2007 Jan;9(1):3-4 PMID: 17227400
  32. A human gut microbial gene catalogue established by metagenomic sequencing.
    Nature. 2010 Mar 4;464(7285):59-65 PMID: 20203603
  33. Pharmaco-metabonomic phenotyping and personalized drug treatment.
    Nature. 2006 Apr 20;440(7087):1073-7 PMID: 16625200
  34. Direct quantitative trait locus mapping of mammalian metabolic phenotypes in diabetic and normoglycemic rat models.
    Nat Genet. 2007 May;39(5):666-72 PMID: 17435758
  35. Rapid and noninvasive diagnosis of the presence and severity of coronary heart disease using 1H-NMR-based metabonomics.
    Nat Med. 2002 Dec;8(12):1439-44 PMID: 12447357
  36. A primitive T cell-independent mechanism of intestinal mucosal IgA responses to commensal bacteria.
    Science. 2000 Jun 23;288(5474):2222-6 PMID: 10864873
  37. Is type 2 diabetes an operable intestinal disease? A provocative yet reasonable hypothesis.
    Diabetes Care. 2008 Feb;31 Suppl 2:S290-6 PMID: 18227499
  38. A molecular view of the intestinal ecosystem.
    Curr Issues Intest Microbiol. 2000 Mar;1(1):1-12 PMID: 11709849
  39. Alleviating cancer drug toxicity by inhibiting a bacterial enzyme.
    Science. 2010 Nov 5;330(6005):831-5 PMID: 21051639
  40. Human gut microbiota in obesity and after gastric bypass.
    Proc Natl Acad Sci U S A. 2009 Feb 17;106(7):2365-70 PMID: 19164560
  41. Characterization of the inhabitancy of mouse intestinal bacteria (MIB) in rodents and humans by real-time PCR with group-specific primers.
    Microbiol Immunol. 2007;51(4):349-57 PMID: 17446674
  42. Prebiotics, probiotics and helminths: the 'natural' solution?
    Dig Dis. 2009;27(3):412-7 PMID: 19786773
  43. Quantitative phylogenetic assessment of microbial communities in diverse environments.
    Science. 2007 Feb 23;315(5815):1126-30 PMID: 17272687
  44. Therapeutic manipulation of the enteric microflora in inflammatory bowel diseases: antibiotics, probiotics, and prebiotics.
    Gastroenterology. 2004 May;126(6):1620-33 PMID: 15168372
  45. Successful treatment of fulminant Clostridium difficile infection with fecal bacteriotherapy.
    Ann Intern Med. 2008 Apr 15;148(8):632-3 PMID: 18413636
  46. Gut microorganisms, mammalian metabolism and personalized health care.
    Nat Rev Microbiol. 2005 May;3(5):431-8 PMID: 15821725
  47. Global systems biology and personalized healthcare solutions.
    Discov Med. 2006 Apr;6(32):63-70 PMID: 17234128
  48. Pharmacometabonomic identification of a significant host-microbiome metabolic interaction affecting human drug metabolism.
    Proc Natl Acad Sci U S A. 2009 Aug 25;106(34):14728-33 PMID: 19667173
  49. A core gut microbiome in obese and lean twins.
    Nature. 2009 Jan 22;457(7228):480-4 PMID: 19043404
  50. Reshaping the gut microbiome with bacterial transplantation and antibiotic intake.
    Genome Res. 2010 Oct;20(10):1411-9 PMID: 20736229
  51. The role of oral hygiene in inflammatory bowel disease.
    Dig Dis Sci. 2011 Jan;56(1):170-5 PMID: 20458622
  52. Effects of intestinal microflora and the environment on the development of asthma and allergy.
    Springer Semin Immunopathol. 2004 Feb;25(3-4):257-70 PMID: 15007630
  53. Gnotobiotic rats harboring human intestinal microbiota as a model for studying cholesterol-to-coprostanol conversion.
    FEMS Microbiol Ecol. 2004 Mar 1;47(3):337-43 PMID: 19712322
  54. Xylan-regulated delivery of human keratinocyte growth factor-2 to the inflamed colon by the human anaerobic commensal bacterium Bacteroides ovatus.
    Gut. 2010 Apr;59(4):461-9 PMID: 19736360
  55. Ecological control of the gastrointestinal tract. The role of probiotic flora.
    Gut. 1998 Jan;42(1):2-7 PMID: 9505873
  56. Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics.
    J Nutr. 1995 Jun;125(6):1401-12 PMID: 7782892
  57. Transcriptional activity of the dominant gut mucosal microbiota in chronic inflammatory bowel disease patients.
    J Med Microbiol. 2010 Sep;59(Pt 9):1114-1122 PMID: 20522625
  58. Functional metagenomics: a high throughput screening method to decipher microbiota-driven NF-κB modulation in the human gut.
    PLoS One. 2010 Sep 30;5(9): PMID: 20927194
  59. Metabonomic and microbiological analysis of the dynamic effect of vancomycin-induced gut microbiota modification in the mouse.
    J Proteome Res. 2008 Sep;7(9):3718-28 PMID: 18698804
  60. Structure and function of the intestinal epithelial barrier in health and disease.
    Monogr Pathol. 1990;(31):306-24 PMID: 2406578
  61. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43.
    Nature. 2009 Oct 29;461(7268):1282-6 PMID: 19865172
  62. The role of gut microbiota in drug response.
    Curr Pharm Des. 2009;15(13):1519-23 PMID: 19442168
  63. Comparative metagenomics revealed commonly enriched gene sets in human gut microbiomes.
    DNA Res. 2007 Aug 31;14(4):169-81 PMID: 17916580
  64. Obesity alters gut microbial ecology.
    Proc Natl Acad Sci U S A. 2005 Aug 2;102(31):11070-5 PMID: 16033867
  65. Synbiotics reduce postoperative infectious complications: a randomized controlled trial in biliary cancer patients undergoing hepatectomy.
    Langenbecks Arch Surg. 2005 Apr;390(2):104-13 PMID: 15711820
  66. Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis.
    Cell. 2004 Jul 23;118(2):229-41 PMID: 15260992
  67. Succession of microbial consortia in the developing infant gut microbiome.
    Proc Natl Acad Sci U S A. 2011 Mar 15;108 Suppl 1:4578-85 PMID: 20668239
  68. Lactobacillus helveticus and Bifidobacterium longum taken in combination reduce the apoptosis propensity in the limbic system after myocardial infarction in a rat model.
    Br J Nutr. 2009 Nov;102(10):1420-5 PMID: 19563693
  69. Identification and characterisation of Pseudomonas 16S ribosomal DNA from ileal biopsies of children with Crohn's disease.
    PLoS One. 2008;3(10):e3578 PMID: 18974839
  70. Rapid and noninvasive metabonomic characterization of inflammatory bowel disease.
    J Proteome Res. 2007 Feb;6(2):546-51 PMID: 17269711
  71. 'Metabonomics': understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data.
    Xenobiotica. 1999 Nov;29(11):1181-9 PMID: 10598751
  72. Susceptibility of human metabolic phenotypes to dietary modulation.
    J Proteome Res. 2006 Oct;5(10):2780-8 PMID: 17022649
  73. Viruses in the faecal microbiota of monozygotic twins and their mothers.
    Nature. 2010 Jul 15;466(7304):334-8 PMID: 20631792
  74. Bacterial community variation in human body habitats across space and time.
    Science. 2009 Dec 18;326(5960):1694-7 PMID: 19892944
  75. Experimental models for studying the microbial ecology in the intestinal tract.
    Acta Gastroenterol Latinoam. 1989;19(4):219-26 PMID: 2561802
  76. The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice.
    Sci Transl Med. 2009 Nov 11;1(6):6ra14 PMID: 20368178
  77. Ecological and evolutionary forces shaping microbial diversity in the human intestine.
    Cell. 2006 Feb 24;124(4):837-48 PMID: 16497592
  78. Global metabolic phenotyping in an experimental laparotomy model of surgical trauma.
    J Proteome Res. 2011 Jan 7;10(1):277-87 PMID: 21105667
  79. Temperature gradient gel electrophoresis analysis of 16S rRNA from human fecal samples reveals stable and host-specific communities of active bacteria.
    Appl Environ Microbiol. 1998 Oct;64(10):3854-9 PMID: 9758810
  80. Effects of the probiotic Bifidobacterium infantis in the maternal separation model of depression.
    Neuroscience. 2010 Nov 10;170(4):1179-88 PMID: 20696216
  81. Microbiomic analysis of the bifidobacterial population in the human distal gut.
    ISME J. 2009 Jun;3(6):745-51 PMID: 19295640
  82. A top-down systems biology view of microbiome-mammalian metabolic interactions in a mouse model.
    Mol Syst Biol. 2007;3:112 PMID: 17515922
  83. Shotgun metaproteomics of the human distal gut microbiota.
    ISME J. 2009 Feb;3(2):179-89 PMID: 18971961
  84. Culture-independent analysis of the gut microbiota in colorectal cancer and polyposis.
    Environ Microbiol. 2008 Mar;10(3):789-98 PMID: 18237311
  85. Human gut microbiome adopts an alternative state following small bowel transplantation.
    Proc Natl Acad Sci U S A. 2009 Oct 6;106(40):17187-92 PMID: 19805153
  86. Gut microbiota: a potential new territory for drug targeting.
    Nat Rev Drug Discov. 2008 Feb;7(2):123-9 PMID: 18239669
  87. Topographical variation in murine intestinal metabolic profiles in relation to microbiome speciation and functional ecological activity.
    J Proteome Res. 2009 Jul;8(7):3464-74 PMID: 19492798
  88. Bacteriotherapy using fecal flora: toying with human motions.
    J Clin Gastroenterol. 2004 Jul;38(6):475-83 PMID: 15220681
  89. The core gut microbiome, energy balance and obesity.
    J Physiol. 2009 Sep 1;587(Pt 17):4153-8 PMID: 19491241
  90. Therapeutic implications of manipulating and mining the microbiota.
    J Physiol. 2009 Sep 1;587(Pt 17):4175-9 PMID: 19505978
  91. Therapy and epidemiology of autism--clostridial spores as key elements.
    Med Hypotheses. 2008;70(3):508-11 PMID: 17904761
  92. A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome.
    Gut Pathog. 2009 Mar 19;1(1):6 PMID: 19338686
  93. Diversity of the human intestinal microbial flora.
    Science. 2005 Jun 10;308(5728):1635-8 PMID: 15831718
  94. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system.
    Cell. 2005 Jul 15;122(1):107-18 PMID: 16009137
  95. Drug metabolome of the simvastatin formed by human intestinal microbiota in vitro.
    Mol Biosyst. 2011 Feb;7(2):437-46 PMID: 21060933
  96. Early life stress alters behavior, immunity, and microbiota in rats: implications for irritable bowel syndrome and psychiatric illnesses.
    Biol Psychiatry. 2009 Feb 1;65(3):263-7 PMID: 18723164
  97. TLR4 signalling in the intestine in health and disease.
    Biochem Soc Trans. 2007 Dec;35(Pt 6):1473-8 PMID: 18031248
  98. Metagenomic analysis of the human distal gut microbiome.
    Science. 2006 Jun 2;312(5778):1355-9 PMID: 16741115
  99. Phylogenetic and gene-centric metagenomics of the canine intestinal microbiome reveals similarities with humans and mice.
    ISME J. 2011 Apr;5(4):639-49 PMID: 20962874
Article Info
Journal
Genome medicine
Abbr.
Genome Med
ISSN
1756-994X
Published
2011-03-04
Epub
2011-00-04
Pages
14
Language
English
Region
England
NLM ID
101475844
PMCID
PMC3092099
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