title: Advances in inflammatory bowel disease pathogenesis: linking host genetics and the microbiome.
abstract: Studies of the genetics underlying inflammatory bowel diseases have increased our understanding of the pathways involved in both ulcerative colitis and Crohn's disease and focused attention on the role of the microbiome in these diseases. Full understanding of pathogenesis will require a comprehensive grasp of the delicate homeostasis between gut bacteria and the human host. In this review, we present current evidence of microbiome-gene interactions in the context of other known risk factors and mechanisms, and describe the next steps necessary to pair genetic variant and microbiome sequencing data from patient cohorts. We discuss the concept of dysbiosis, proposing that the functional composition of the gut microbiome may provide a more consistent definition of dysbiosis and may more readily provide evidence of genome-microbiome interactions in future exploratory studies.
authors.affiliation: Broad Institute of Harvard and Massachusetts Institute of Technology, , Cambridge, Massachusetts, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Knights
authors.forename: Kara G
authors.initials: KG
authors.lastname: Lassen
authors.forename: Ramnik J
authors.initials: RJ
authors.lastname: Xavier
mesh_terms: D001419:Bacteria / Q000276:immunology; D020022:Genetic Predisposition to Disease; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics* / Q000276:immunology / Q000382:microbiology*; D007422:Intestines / Q000382:microbiology; D064307:Microbiota; D010641:Phenotype; D015398:Signal Transduction / Q000235:genetics
keywords: CROHN'S DISEASE; GENETICS; INFLAMMATORY BOWEL DISEASE; INTESTINAL BACTERIA; ULCERATIVE COLITIS
references.citation: Genome Biol Evol. 2013;5(3):578-90
references.pmid: 23431001
references.citation: Science. 2012 Sep 21;337(6101):1553-6
references.pmid: 22923434
references.citation: Nature. 2001 May 31;411(6837):603-6
references.pmid: 11385577
references.citation: Infect Immun. 2009 Apr;77(4):1376-82
references.pmid: 19139201
references.citation: Cell Host Microbe. 2007 Aug 16;2(2):119-29
references.pmid: 18005726
references.citation: Nature. 2012 Feb 15;482(7385):339-46
references.pmid: 22337053
references.citation: Curr Opin Gastroenterol. 2010 Jul;26(4):327-31
references.pmid: 20445446
references.citation: Gastroenterology. 2010 Dec;139(6):1844-1854.e1
references.pmid: 20816835
references.citation: Science. 2012 Sep 7;337(6099):1190-5
references.pmid: 22955828
references.citation: Nat Genet. 2010 Dec;42(12):1118-25
references.pmid: 21102463
references.citation: PLoS Genet. 2010 Apr 01;6(4):e1000888
references.pmid: 20369019
references.citation: Appl Environ Microbiol. 2012 Jan;78(2):511-8
references.pmid: 22081579
references.citation: J Exp Med. 2012 Aug 27;209(9):1595-609
references.pmid: 22891275
references.citation: Proc Natl Acad Sci U S A. 2010 Nov 16;107(46):19961-6
references.pmid: 21041655
references.citation: J Biol Chem. 2012 Jan 2;287(1):286-298
references.pmid: 22069308
references.citation: Nature. 2012 Nov 1;491(7422):119-24
references.pmid: 23128233
references.citation: Curr Opin Immunol. 2012 Aug;24(4):392-7
references.pmid: 22673877
references.citation: Nature. 2012 Jun 13;486(7402):207-14
references.pmid: 22699609
references.citation: Gut. 2012 Nov;61(11):1610-8
references.pmid: 21900548
references.citation: Nature. 2012 Sep 20;489(7416):443-6
references.pmid: 22895189
references.citation: Nature. 2012 Nov 1;491(7422):56-65
references.pmid: 23128226
references.citation: PLoS Comput Biol. 2013;9(1):e1002863
references.pmid: 23326225
references.citation: Immunity. 2012 Dec 14;37(6):1116-29
references.pmid: 23200826
references.citation: Nat Genet. 2011 Oct 09;43(11):1066-73
references.pmid: 21983784
references.citation: J Dent Res. 2012 Jul;91(7 Suppl):21S-28S
references.pmid: 22699663
references.citation: J Clin Invest. 2013 Feb;123(2):700-11
references.pmid: 23281400
references.citation: Autoimmunity. 2013 Feb;46(1):21-31
references.pmid: 23039363
references.citation: Nature. 2012 Jul 5;487(7405):104-8
references.pmid: 22722865
references.citation: J Exp Med. 2012 Oct 22;209(11):2127-35
references.pmid: 23008335
references.citation: PLoS One. 2012;7(2):e31151
references.pmid: 22363568
references.citation: Nature. 2001 May 31;411(6837):599-603
references.pmid: 11385576
references.citation: Nat Immunol. 2004 Oct;5(10):987-95
references.pmid: 15454922
references.citation: Gut Microbes. 2010 Jul;1(4):254-268
references.pmid: 21327032
references.citation: Int J Syst Evol Microbiol. 2002 Sep;52(Pt 5):1615-1620
references.pmid: 12361264
references.citation: N Engl J Med. 2009 Nov 19;361(21):2066-78
references.pmid: 19923578
references.citation: Science. 2011 Oct 7;334(6052):105-8
references.pmid: 21885731
references.citation: Nature. 2012 Sep 6;489(7414):57-74
references.pmid: 22955616
references.citation: Genome Biol. 2011;12(5):R50
references.pmid: 21624126
references.citation: Cell. 2011 May 27;145(5):745-57
references.pmid: 21565393
references.citation: J Biol Chem. 2012 Sep 7;287(37):30932-40
references.pmid: 22952232
references.citation: Inflamm Bowel Dis. 2012 Jan;18(1):187-93
references.pmid: 21425211
references.citation: Annu Rev Immunol. 2010;28:573-621
references.pmid: 20192811
references.citation: Inflamm Bowel Dis. 2011 Apr;17(4):907-16
references.pmid: 20722056
references.citation: N Engl J Med. 2013 Jan 31;368(5):407-15
references.pmid: 23323867
references.citation: Science. 2012 Jun 8;336(6086):1325-9
references.pmid: 22582016
references.citation: Science. 2012 Feb 17;335(6070):823-8
references.pmid: 22344438
references.citation: Inflamm Bowel Dis. 2008 Oct;14(10):1432-42
references.pmid: 18484669
references.citation: J Immunol. 2010 Feb 15;184(4):1710-20
references.pmid: 20083652
references.citation: Nature. 2011 May 12;473(7346):174-80
references.pmid: 21508958
references.citation: Genome Biol. 2012 Apr 16;13(9):R79
references.pmid: 23013615
references.citation: Nat Med. 2010 Jan;16(1):90-7
references.pmid: 19966812
references.citation: Nature. 2012 Jul 25;487(7408):477-81
references.pmid: 22837003