title: Recent advances in characterizing the gastrointestinal microbiome in Crohn's disease: a systematic review.
abstract: BACKGROUND
  The intestinal microbiota is involved in the pathogenesis of inflammatory bowel disease. A reduction in the diversity of the intestinal microbiota as well as specific taxonomic and functional shifts have been reported in Crohn's disease and may play a central role in the inflammatory process. The aim was to systematically review recent developments in the structural and functional changes observed in the gastrointestinal microbiome in patients with Crohn's Disease.
  
  
  RESULTS
  Seventy-two abstracts were included in this review. The effects of host genetics, disease phenotype, and inflammatory bowel disease treatment on the gastrointestinal microbiome in Crohn's disease were reviewed, and taxonomic shifts in patients with early and established disease were described. The relative abundance of Bacteroidetes is increased and Firmicutes decreased in Crohn's disease compared with healthy controls. Enterobacteriaceae, specifically Eschericia coli, is enriched in Crohn's disease. Faecalibacterium prausnitzii is found at lower abundance in Crohn's disease and in those with postoperative recurrence. Observed functional changes include major shifts in oxidative stress pathways, a decrease in butanoate and propanoate metabolism gene expression, lower levels of butyrate, and other short-chain fatty acids, decreased carbohydrate metabolism, and decreased amino acid biosynthesis.
  
  
  CONCLUSIONS
  Changes in microbial composition and function have been described, although a causative role remains to be established. Larger, prospective, and longitudinal studies are required with deep interrogation of the microbiome if causality is to be determined, and refined microbial manipulation is to emerge as a focused therapy.
authors.affiliation: *Department of Gastroenterology, St Vincent's Hospital Melbourne, Australia; †Department of Pathology, University of Melbourne, Australia; ‡Imperial College, London, United Kingdom; and §Enteric Virus Group, Murdoch Children's Research Institute, Melbourne, Australia.
authors.forename: Emily K
authors.initials: EK
authors.lastname: Wright
authors.forename: Michael A
authors.initials: MA
authors.lastname: Kamm
authors.forename: Shu Mei
authors.initials: SM
authors.lastname: Teo
authors.forename: Michael
authors.initials: M
authors.lastname: Inouye
authors.forename: Josef
authors.initials: J
authors.lastname: Wagner
authors.forename: Carl D
authors.initials: CD
authors.lastname: Kirkwood
mesh_terms: D041963:Bacteroidetes; D003424:Crohn Disease / Q000382:microbiology* / Q000503:physiopathology; D004926:Escherichia coli; D000068536:Bacillota; D000069196:Gastrointestinal Microbiome; D006801:Humans
references.citation: J Pediatr. 2010 Aug;157(2):240-244.e1
references.pmid: 20400104
references.citation: Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15451-5
references.pmid: 12432102
references.citation: Gastroenterology. 2010 Dec;139(6):1844-1854.e1
references.pmid: 20816835
references.citation: J Clin Microbiol. 2012 Oct;50(10):3258-66
references.pmid: 22837318
references.citation: Bioessays. 2013 Sep;35(9):810-7
references.pmid: 23836415
references.citation: Dis Colon Rectum. 2010 Nov;53(11):1530-6
references.pmid: 20940602
references.citation: Inflamm Bowel Dis. 2012 May;18(5):935-42
references.pmid: 21987382
references.citation: Nature. 2012 Nov 1;491(7422):119-24
references.pmid: 23128233
references.citation: Environ Microbiol. 2012 Oct 15;:
references.pmid: 23286720
references.citation: BMC Gastroenterol. 2013 Aug 22;13:131
references.pmid: 23964800
references.citation: Gut. 2011 Oct;60(10):1354-62
references.pmid: 21421666
references.citation: Nature. 2012 Jun 13;486(7402):207-14
references.pmid: 22699609
references.citation: Biomed Rep. 2014 May;2(3):370-373
references.pmid: 24748976
references.citation: Inflamm Bowel Dis. 2007 Jun;13(6):675-83
references.pmid: 17262808
references.citation: Nature. 2006 Dec 21;444(7122):1027-31
references.pmid: 17183312
references.citation: Int J Med Microbiol. 2008 Jul;298(5-6):463-72
references.pmid: 17897884
references.citation: ISME J. 2008 Jul;2(7):716-27
references.pmid: 18401439
references.citation: PLoS Med. 2009 Jul 21;6(7):e1000097
references.pmid: 19621072
references.citation: Gut. 2014 Oct;63(10):1578-86
references.pmid: 24398881
references.citation: Zhonghua Yi Xue Za Zhi. 2013 Sep 24;93(36):2884-9
references.pmid: 24373401
references.citation: Cell Metab. 2013 Mar 5;17(3):317-8
references.pmid: 23473028
references.citation: Gastroenterology. 2014 May;146(6):1513-24
references.pmid: 24440671
references.citation: PLoS One. 2013 Jun 20;8(6):e66074
references.pmid: 23840402
references.citation: Aliment Pharmacol Ther. 2009 Jan;29(1):75-82
references.pmid: 18945264
references.citation: Proc Natl Acad Sci U S A. 2011 Mar 15;108 Suppl 1:4554-61
references.pmid: 20847294
references.citation: Genome Res. 2012 Feb;22(2):299-306
references.pmid: 22009989
references.citation: J Clin Microbiol. 2010 Nov;48(11):4279-82
references.pmid: 20861337
references.citation: Nature. 2001 May 31;411(6837):603-6
references.pmid: 11385577
references.citation: Am J Physiol Gastrointest Liver Physiol. 2011 Nov;301(5):G799-807
references.pmid: 21737778
references.citation: Gut. 2012 Jul;61(7):997-1006
references.pmid: 22180058
references.citation: Gut. 2014 Oct;63(10):1566-77
references.pmid: 24436141
references.citation: Curr Opin Gastroenterol. 2014 Jan;30(1):34-9
references.pmid: 24241245
references.citation: Gastroenterology. 2007 Feb;132(2):576-86
references.pmid: 17258734
references.citation: Nat Rev Gastroenterol Hepatol. 2012 Oct;9(10):599-608
references.pmid: 22907164
references.citation: Gastroenterology. 2005 Apr;128(4):856-61
references.pmid: 15825069
references.citation: BMC Microbiol. 2011 Jan 10;11:7
references.pmid: 21219646
references.citation: Am J Gastroenterol. 2012 Dec;107(12):1913-22
references.pmid: 23044767
references.citation: Proc Natl Acad Sci U S A. 2008 Oct 28;105(43):16731-6
references.pmid: 18936492
references.citation: Nature. 2010 Mar 4;464(7285):59-65
references.pmid: 20203603
references.citation: PLoS Biol. 2008 Nov 18;6(11):e280
references.pmid: 19018661
references.citation: Aliment Pharmacol Ther. 2012 Sep;36(6):503-16
references.pmid: 22827693
references.citation: J Nutr. 2004 Sep;134(9):2450S-2454S
references.pmid: 15333741
references.citation: J Gastroenterol Hepatol. 2013 Apr;28(4):613-9
references.pmid: 23216550
references.citation: Gastroenterology. 2014 May;146(6):1554-63
references.pmid: 24486051
references.citation: Nature. 2014 Jan 23;505(7484):559-63
references.pmid: 24336217
references.citation: Int J Med Microbiol. 2014 May;304(3-4):464-75
references.pmid: 24713205
references.citation: Inflamm Bowel Dis. 2006 Feb;12(2):106-11
references.pmid: 16432374
references.citation: Gut. 2000 Sep;47(3):397-403
references.pmid: 10940278
references.citation: J Clin Invest. 2014 Aug;124(8):3617-33
references.pmid: 25003194
references.citation: J Med Microbiol. 2006 Aug;55(Pt 8):1141-1149
references.pmid: 16849736
references.citation: BMC Gastroenterol. 2013 Jan 26;13:20
references.pmid: 23351032
references.citation: Int J Med Microbiol. 2011 Aug;301(6):475-9
references.pmid: 21616711
references.citation: Gut Microbes. 2012 Nov-Dec;3(6):572-6
references.pmid: 22895081
references.citation: Science. 2011 Oct 7;334(6052):105-8
references.pmid: 21885731
references.citation: Gastroenterology. 2002 Jan;122(1):44-54
references.pmid: 11781279
references.citation: Inflamm Bowel Dis. 2011 Jan;17(1):179-84
references.pmid: 20839241
references.citation: Nature. 2009 Jan 22;457(7228):480-4
references.pmid: 19043404
references.citation: Inflamm Bowel Dis. 2012 Jun;18(6):1092-100
references.pmid: 22102318
references.citation: Genome Biol. 2011;12(5):R50
references.pmid: 21624126
references.citation: Gut. 2006 Feb;55(2):205-11
references.pmid: 16188921
references.citation: Elife. 2013 Apr 16;2:e00458
references.pmid: 23599893
references.citation: J Clin Microbiol. 2006 Nov;44(11):4136-41
references.pmid: 16988016
references.citation: Inflamm Bowel Dis. 2010 Dec;16(12):2034-42
references.pmid: 20848492
references.citation: Inflamm Bowel Dis. 2009 May;15(5):653-60
references.pmid: 19023901
references.citation: Lancet. 1991 Sep 28;338(8770):771-4
references.pmid: 1681159
references.citation: J Clin Microbiol. 2005 Sep;43(9):4654-8
references.pmid: 16145122
references.citation: Inflamm Bowel Dis. 2014 Jun;20(6):978-86
references.pmid: 24788220
references.citation: J Pediatr Gastroenterol Nutr. 2008 May;46(5):486-95
references.pmid: 18493202
references.citation: Inflamm Bowel Dis. 2007 Aug;13(8):984-92
references.pmid: 17417801
references.citation: Gut. 2011 May;60(5):631-7
references.pmid: 21209126
references.citation: Am J Gastroenterol. 2002 Apr;97(4):939-46
references.pmid: 12003430
references.citation: J Gastroenterol Hepatol. 2015 Feb;30(2):268-78
references.pmid: 25087692
references.citation: PLoS One. 2011;6(7):e23035
references.pmid: 21829582
references.citation: Inflamm Bowel Dis. 2014 Mar;20(3):417-30
references.pmid: 24418903
references.citation: Gastroenterology. 1995 Jun;108(6):1617-21
references.pmid: 7768364
references.citation: J Gastroenterol. 2011 Apr;46(4):479-86
references.pmid: 21253779
references.citation: Genome Biol. 2012 Apr 16;13(9):R79
references.pmid: 23013615
references.citation: PLoS One. 2013;8(3):e59260
references.pmid: 23516617
references.citation: J Clin Microbiol. 2006 Nov;44(11):3980-8
references.pmid: 16988018
references.citation: World J Gastroenterol. 2009 Nov 14;15(42):5287-94
references.pmid: 19908336
references.citation: Antimicrob Agents Chemother. 2011 Apr;55(4):1494-503
references.pmid: 21282433
references.citation: PLoS One. 2012;7(11):e49138
references.pmid: 23209564
references.citation: Nature. 2011 Jun 15;474(7351):307-17
references.pmid: 21677747
references.citation: Gut. 2016 Jun;65(6):944-53
references.pmid: 25856344
references.citation: Science. 2005 Jun 10;308(5728):1635-8
references.pmid: 15831718
references.citation: Cell Host Microbe. 2014 Mar 12;15(3):382-392
references.pmid: 24629344
references.citation: Microb Ecol. 2013 Aug;66(2):462-70
references.pmid: 23733170
references.citation: Gut. 2004 May;53(5):685-93
references.pmid: 15082587
references.citation: PLoS One. 2012;7(6):e26284
references.pmid: 22719818