期刊论文详细信息
BMC Gastroenterology
Association of gut microbiota with post-operative clinical course in Crohn’s disease
Steven E Brenner1  Susanna Repo1  David AW Soergel1  Neelendu Dey2 
[1]Department of Plant and Microbial Biology, University of California, Berkeley, 461 Koshland Hall, Berkeley, CA 94720-3102, USA
[2]Current address: Department of Medicine, Division of Gastroenterology, Washington University School of Medicine, Saint Louis, MO 63108, USA
关键词: 16S rRNA gene;    Microbial profiling;    Next-generation sequencing;    Gut microbiome;    Crohn's disease;   
Others  :  857661
DOI  :  10.1186/1471-230X-13-131
 received in 2013-01-08, accepted in 2013-08-06,  发布年份 2013
PDF
【 摘 要 】

Background

The gut microbiome is altered in Crohn’s disease. Although individual taxa have been correlated with post-operative clinical course, global trends in microbial diversity have not been described in this context.

Methods

We collected mucosal biopsies from the terminal ileum and ascending colon during surgery and post-operative colonoscopy in 6 Crohn’s patients undergoing ileocolic resection (and 40 additional Crohn’s and healthy control patients undergoing either surgery or colonoscopy). Using next-generation sequencing technology, we profiled the gut microbiota in order to identify changes associated with remission or recurrence of inflammation.

Results

We performed 16S ribosomal profiling using 101 base-pair single-end sequencing on the Illumina GAIIx platform with deep coverage, at an average depth of 1.3 million high quality reads per sample. At the time of surgery, Crohn’s patients who would remain in remission were more similar to controls and more species-rich than Crohn’s patients with subsequent recurrence. Patients remaining in remission also exhibited greater stability of the microbiota through time.

Conclusions

These observations permitted an association of gut microbial profiles with probability of recurrence in this limited single-center study. These results suggest that profiling the gut microbiota may be useful in guiding treatment of Crohn’s patients undergoing surgery.

【 授权许可】

   
2013 Dey et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20140723083240453.pdf 691KB PDF download
41KB Image download
37KB Image download
67KB Image download
【 图 表 】

【 参考文献 】
  • [1]Abraham C, Cho JH: Inflammatory bowel disease. N Engl J Med 2009, 361:2066-2078.
  • [2]Frank DN, St Amand AL, Feldman RA, Boedeker EC, Harpaz N, Pace NR: Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci USA 2007, 104:13780-13785.
  • [3]Neut C, Bulois P, Desreumaux P, Membré J-M, Lederman E, Gambiez L, Cortot A, Quandalle P, van Kruiningen H, Colombel J-F: Changes in the bacterial flora of the neoterminal ileum after ileocolonic resection for Crohn’s disease. Am J Gastroenterol 2002, 97:939-946.
  • [4]Dicksved J, Halfvarson J, Rosenquist M, Järnerot G, Tysk C, Apajalahti J, Engstrand L, Jansson JK: Molecular analysis of the gut microbiota of identical twins with Crohn’s disease. ISME J 2008, 2:716-727.
  • [5]Bibiloni R, Mangold M, Madsen KL, Fedorak RN, Tannock GW: The bacteriology of biopsies differs between newly diagnosed, untreated, Crohn’s disease and ulcerative colitis patients. J Med Microbiol 2006, 55(Pt 8):1141-1149.
  • [6]Swidsinski A, Weber J, Loening-Baucke V, Hale LP, Lochs H: Spatial organization and composition of the mucosal flora in patients with inflammatory bowel disease. J Clin Microbiol 2005, 43:3380-3389.
  • [7]Willing BP, Dicksved J, Halfvarson J, Andersson AF, Lucio M, Zheng Z, Järnerot G, Tysk C, Jansson JK, Engstrand L: A pyrosequencing study in twins shows that gastrointestinal microbial profiles vary with inflammatory bowel disease phenotypes. Gastroenterology 2010, 139:1844-1854.
  • [8]Frank DN, Robertson CE, Hamm CM, Kpadeh Z, Zhang T, Chen H, Zhu W, Sartor RB, Boedeker EC, Harpaz N, Pace NR, Li E: Disease phenotype and genotype are associated with shifts in intestinal‒associated microbiota in inflammatory bowel diseases. Inflamm Bowel Dis 2011, 17:179-184.
  • [9]Sokol H, Pigneur B, Watterlot L, Lakhdari O, Bermúdez-Humarán LG, Gratadoux J-J, Blugeon S, Bridonneau C, Furet J-P, Corthier G, Grangette C, Vasquez N, Pochart P, Trugnan G, Thomas G, Blottière HM, Doré J, Marteau P, Seksik P, Langella P: Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci USA 2008, 105:16731-16736.
  • [10]Terdiman JP: Prevention of postoperative recurrence in Crohn’s disease. Clin Gastroenterol Hepatol 2008, 6:616-620.
  • [11]Regueiro M, Schraut W, Baidoo L, Kip KE, Sepulveda AR, Pesci M, Harrison J, Plevy SE: Infliximab prevents Crohn’s disease recurrence after ileal resection. Gastroenterology 2009, 136:441-450.
  • [12]Rutgeerts P, Geboes K, Vantrappen G, Kerremans R, Coenegrachts JL, Coremans G: Natural history of recurrent Crohn’s disease at the ileocolonic anastomosis after curative surgery. Gut 1984, 25:665-672.
  • [13]Dave M, Johnson LA, Walk ST, Young VB, Stidham RW, Chaudhary MN, Funnell J, Higgins PDR: A randomised trial of sheathed versus standard forceps for obtaining uncontaminated biopsy specimens of microbiota from the terminal ileum. Gut 2011, 60:1043-1049.
  • [14]Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, Gill SR, Nelson KE, Relman DA: Diversity of the human intestinal microbial flora. Science 2005, 308:1635-1638.
  • [15]Walker AW, Sanderson JD, Churcher C, Parkes GC, Hudspith BN, Rayment N, Brostoff J, Parkhill J, Dougan G, Petrovska L: High-throughput clone library analysis of the mucosa-associated microbiota reveals dysbiosis and differences between inflamed and non-inflamed regions of the intestine in inflammatory bowel disease. BMC Microbiol 2011, 11:7. BioMed Central Full Text
  • [16]Caporaso JG, Kuczynski J, Stombaugh J, Bittinger K, Bushman FD, Costello EK, Fierer N, Peña AG, Goodrich JK, Gordon JI, Huttley GA, Kelley ST, Knights D, Koenig JE, Ley RE, Lozupone CA, McDonald D, Muegge BD, Pirrung M, Reeder J, Sevinsky JR, Turnbaugh PJ, Walters WA, Widmann J, Yatsunenko T, Zaneveld J, Knight R: QIIME allows analysis of high-throughput community sequencing data. Nat Methods 2010, 7:335-336.
  • [17]Haas BJ, Gevers D, Earl AM, Feldgarden M, Ward DV, Giannoukos G, Ciulla D, Tabbaa D, Highlander SK, Sodergren E, Methé B, DeSantis TZ, Petrosino JF, Knight R, Birren BW: Chimeric 16S rRNA sequence formation and detection in Sanger and 454-pyrosequenced PCR amplicons. Genome Res 2011, 21:494-504.
  • [18]Caporaso JG, Bittinger K, Bushman FD, DeSantis TZ, Andersen GL, Knight R: PyNAST: a flexible tool for aligning sequences to a template alignment. Bioinformatics 2010, 26:266-267.
  • [19]Price MN, Dehal PS, Arkin AP: FastTree: computing large minimum evolution trees with profiles instead of a distance matrix. Mol Biol Evol 2009, 26:1641-1650.
  • [20]Wang Q, Garrity GM, Tiedje JM, Cole JR: Naive Bayesian classifier for rapid assignment of rRNA sequences into the new bacterial taxonomy. Appl Environ Microbiol 2007, 73:5261-5267.
  • [21]Chao A: Non-parametric estimation of the number of classes in a population. Scand J Stat 1987, 11:265-270.
  • [22]Faith DP: Phylogenetic pattern and the quantification of organismal biodiversity. Philos Trans R Soc Lond B Biol Sci 1994, 345:45-58.
  • [23]Lozupone C, Knight R: UniFrac: a new phylogenetic method for comparing microbial communities. Appl Environ Microbiol 2005, 71:8228-8235.
  • [24]R Development Core Team: R: A Language and Environment for Statistical Computing. Vienna: R Foundation for Statistical Computing; 2011.
  • [25]Wickham H: Ggplot2: Elegant Graphics for Data Analysis. Springer New York; 2009. http://cran.r-project.org/web/packages/ggplot2/ webcite
  • [26]Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE, Sogin ML, Jones WJ, Roe BA, Affourtit JP, Egholm M, Henrissat B, Heath AC, Knight R, Gordon JI: A core gut microbiome in obese and lean twins. Nature 2009, 457:480-484.
  • [27]Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG, Contreras M, Magris M, Hidalgo G, Baldassano RN, Anokhin AP, Heath AC, Warner B, Reeder J, Kuczynski J, Caporaso JG, Lozupone CA, Lauber C, Clemente JC, Knights D, Knight R, Gordon JI: Human gut microbiome viewed across age and geography. Nature 2012, 486:222-227.
  • [28]Warnes GR, Bolker B, Bonebakker L, Gentleman R, Liaw WHA, Lumley T, Maechler M, Magnusson A, Moeller S, Schwartz M, Venables B: gplots: Various R programming tools for plotting data. 2010.
  • [29]Dethlefsen L, Huse S, Sogin ML, Relman DA: The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing. PLoS Biol 2008, 6:e280.
  • [30]Ley RE, Turnbaugh PJ, Klein S, Gordon JI: Microbial ecology: human gut microbes associated with obesity. Nature 2006, 444:1022-1023.
  • [31]Bäckhed F, Ley RE, Sonnenburg JL, Peterson DA, Gordon JI: Host-bacterial mutualism in the human intestine. Science 2005, 307:1915-1920.
  • [32]Muegge BD, Kuczynski J, Knights D, Clemente JC, González A, Fontana L, Henrissat B, Knight R, Gordon JI: Diet Drives Convergence in Gut Microbiome Functions Across Mammalian Phylogeny and Within Humans. Science 2011, 332:970-974.
  • [33]Huse SM, Welch DM, Morrison HG, Sogin ML: Ironing out the wrinkles in the rare biosphere through improved OTU clustering. Environ Microbiol 2010, 12:1889-1898.
  • [34]Soergel DAW: Computational Methods for Evaluating Microbial Diversity (Ph.D. dissertation, University of California, Berkeley). Berkeley: Ph.D. dissertation. University of California; 2010.
  • [35]Degnan PH, Ochman H: Illumina-based analysis of microbial community diversity. ISME J 2011, 6:183-194.
  • [36]Kang S, Denman SE, Morrison M, Yu Z, Dore J, Leclerc M, McSweeney CS: Dysbiosis of fecal microbiota in Crohn’s disease patients as revealed by a custom phylogenetic microarray. Inflamm Bowel Dis 2010, 16:2034-2042.
  • [37]Mondot S, Kang S, Furet JP, Aguirre de Carcer D, McSweeney C, Morrison M, Marteau P, Doré J, Leclerc M: Highlighting new phylogenetic specificities of Crohn’s disease microbiota. Inflammatory Bowel Diseases 2011, 17:185-192.
  • [38]Jia W, Whitehead RN, Griffiths L, Dawson C, Waring RH, Ramsden DB, Hunter JO, Cole JA: Is the abundance of Faecalibacterium prausnitzii relevant to Crohn’s disease? FEMS Microbiol Lett 2010, 310:138-144.
  • [39]Joossens M, Huys G, Cnockaert M, De Preter V, Verbeke K, Rutgeerts P, Vandamme P, Vermeire S: Dysbiosis of the faecal microbiota in patients with Crohn’s disease and their unaffected relatives. Gut 2011, 60:631-637.
  • [40]Linskens RK, Huijsdens XW, Savelkoul PH, Vandenbroucke-Grauls CM, Meuwissen SG: The bacterial flora in inflammatory bowel disease: current insights in pathogenesis and the influence of antibiotics and probiotics. Scand J Gastroenterol Suppl 2001, 234:29-40.
  • [41]Andoh A, Tsujikawa T, Sasaki M, Mitsuyama K, Suzuki Y, Matsui T, Matsumoto T, Benno Y, Fujiyama Y: Faecal microbiota profile of Crohn’s disease determined by terminal restriction fragment length polymorphism analysis. Aliment Pharmacol Ther 2009, 29:75-82.
  • [42]Ott SJ, Musfeldt M, Wenderoth DF, Hampe J, Brant O, Fölsch UR, Timmis KN, Schreiber S: Reduction in diversity of the colonic mucosa associated bacterial microflora in patients with active inflammatory bowel disease. Gut 2004, 53:685-693.
  • [43]Martinez-Medina M, Aldeguer X, Gonzalez-Huix F, Acero D, Garcia-Gil LJ: Abnormal microbiota composition in the ileocolonic mucosa of Crohn’s disease patients as revealed by polymerase chain reaction-denaturing gradient gel electrophoresis. Inflamm Bowel Dis 2006, 12:1136-1145.
  • [44]Gophna U, Sommerfeld K, Gophna S, Doolittle WF, Veldhuyzen van Zanten SJO: Differences between tissue-associated intestinal microfloras of patients with Crohn’s disease and ulcerative colitis. J Clin Microbiol 2006, 44:4136-4141.
  • [45]Keighley MR, Arabi Y, Dimock F, Burdon DW, Allan RN, Alexander-Williams J: Influence of inflammatory bowel disease on intestinal microflora. Gut 1978, 19:1099-1104.
  • [46]Manichanh C, Rigottier-Gois L, Bonnaud E, Gloux K, Pelletier E, Frangeul L, Nalin R, Jarrin C, Chardon P, Marteau P, Roca J, Dore J: Reduced diversity of faecal microbiota in Crohn’s disease revealed by a metagenomic approach. Gut 2006, 55:205-211.
  • [47]Hedin CRH, Mullard M, Sharratt E, Jansen C, Sanderson JD, Shirlaw P, Howe LC, Djemal S, Stagg AJ, Lindsay JO, Whelan K: Probiotic and prebiotic use in patients with inflammatory bowel disease: a case–control study. Inflamm Bowel Dis 2010, 16:2099-2108.
  • [48]Scanlan PD, Shanahan F, O’Mahony C, Marchesi JR: Culture-independent analyses of temporal variation of the dominant fecal microbiota and targeted bacterial subgroups in Crohn’s disease. J Clin Microbiol 2006, 44:3980-3988.
  • [49]Judd TA, Day AS, Lemberg DA, Turner D, Leach ST: Update of fecal markers of inflammation in inflammatory bowel disease. J Gastroenterol Hepatol 2011, 26:1493-1499.
  • [50]Butterworth AD, Thomas AG, Akobeng AK: Probiotics for induction of remission in Crohn’s disease. Cochrane Database Syst Rev 2008, 3:CD006634.
  • [51]Doherty G, Bennett G, Patil S, Cheifetz A, Moss AC: Interventions for prevention of post-operative recurrence of Crohn’s disease. Cochrane Database Syst Rev 2009, 4:CD006873.
  • [52]Rolfe VE, Fortun PJ, Hawkey CJ, Bath-Hextall F: Probiotics for maintenance of remission in Crohn’s disease. Cochrane Database Syst Rev 2006, 4:CD004826.
  • [53]Benjamin JL, Hedin CRH, Koutsoumpas A, Ng SC, McCarthy NE, Hart AL, Kamm MA, Sanderson JD, Knight SC, Forbes A, Stagg AJ, Whelan K, Lindsay JO: Randomised, double-blind, placebo-controlled trial of fructo-oligosaccharides in active Crohn’s disease. Gut 2011, 60:923-929.
  • [54]Tolstoy L: Anna Karenina. Penguin Classics; 2004.
  • [55]Barrett JC, Hansoul S, Nicolae DL, Cho JH, Duerr RH, Rioux JD, Brant SR, Silverberg MS, Taylor KD, Barmada MM, Bitton A, Dassopoulos T, Datta LW, Green T, Griffiths AM, Kistner EO, Murtha MT, Regueiro MD, Rotter JI, Schumm LP, Steinhart AH, Targan SR, Xavier RJ, Libioulle C, Sandor C, Lathrop M, Belaiche J, Dewit O, Gut I, Heath S, et al.: Genome-wide association defines more than 30 distinct susceptibility loci for Crohn’s disease. Nat Genet 2008, 40:955-962.
  • [56]Franke A, McGovern DPB, Barrett JC, Wang K, Radford-Smith GL, Ahmad T, Lees CW, Balschun T, Lee J, Roberts R, Anderson CA, Bis JC, Bumpstead S, Ellinghaus D, Festen EM, Georges M, Green T, Haritunians T, Jostins L, Latiano A, Mathew CG, Montgomery GW, Prescott NJ, Raychaudhuri S, Rotter JI, Schumm P, Sharma Y, Simms LA, Taylor KD, Whiteman D, et al.: Genome-wide meta-analysis increases to 71 the number of confirmed Crohn’s disease susceptibility loci. Nat Genet 2010, 42:1118-1125.
  文献评价指标  
  下载次数:28次 浏览次数:24次