Gut microbiome compositional and functional differences between tumor and non-tumor adjacent tissues from cohorts from the US and Spain

Gut Microbes

Volumn 6, Issue 3, 2015, Pages 161-172

  Allali, Imane ^a,b,e   Delgado, Susana ^c   Marron, Pablo Isidro ^d   Astudillo, Aurora ^d   Yeh, Jen Jen ^a   Ghazal, Hassan ^e   Amzazi, Saaïd ^b   Keku, Temitope ^a   Azcarate Peril, M Andrea ^a  

^a UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^b MOHAMMED V UNIVERSITY   (Morocco)

^c DEPARTMENT OF MICROBIOLOGY AND BIOCHEMISTRY OF DAIRY PRODUCTS   (Spain)

^d DEPARTAMENTO DE BIOQUÍMICA Y BIOLOGÍA MOLECULAR   (Spain)

^e FACULTÉ DES SCIENCES   (Morocco)

Author keywords

[No Author keywords available]

Indexed keywords

BACTERIAL TOXIN; MITOGEN ACTIVATED PROTEIN KINASE; RNA 16S; BACTERIAL DNA; RIBOSOME DNA;

ACTINOBACTERIA; ADULT; AGED; AMERICAN; AMPLICON; ARTICLE; BIOINFORMATICS; CAMPYLOBACTER; CLINICAL ARTICLE; COLORECTAL CANCER; CONTROLLED STUDY; DNA ISOLATION; EIKENELLA; FATTY ACID SYNTHESIS; FEMALE; FIRMICUTES; FUSOBACTERIUM; GEMELLA; GENE FUNCTION; GENE SEQUENCE; HUMAN; HUMAN TISSUE; MALE; METAGENOME; MICROBIAL DIVERSITY; MICROBIOME; MIDDLE AGED; PARVIMONAS; SPAIN; STREPTOCOCCUS; VERY ELDERLY; BACTERIUM; CHEMISTRY; CLASSIFICATION; COLORECTAL TUMOR; COMPARATIVE STUDY; DNA SEQUENCE; GENETICS; INTESTINE FLORA; ISOLATION AND PURIFICATION; MICROBIOLOGY; MICROFLORA; UNITED STATES;

ADULT; AGED; AGED, 80 AND OVER; BACTERIA; COLORECTAL NEOPLASMS; DNA, BACTERIAL; DNA, RIBOSOMAL; FEMALE; GASTROINTESTINAL MICROBIOME; HUMANS; MALE; MICROBIOTA; MIDDLE AGED; RNA, RIBOSOMAL, 16S; SEQUENCE ANALYSIS, DNA; SPAIN; UNITED STATES;

EID: 84944459484     PISSN: 19490976     EISSN: 19490984     Source Type: Journal    
DOI: 10.1080/19490976.2015.1039223     Document Type: Article

References (80)

1. GLOBOCAN. Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012. 2012
2. Colorectal Cancer-Facts and Figures. American Cancer Society, 2011-2013:5-9.
3. Karim-Kos HE, de Vries E, Soerjomataram I, Lemmens V, Siesling S, Coebergh JW. Recent trends of cancer in Europe: a combined approach of incidence, survival and mortality for 17 cancer sites since the 1990s. Eur J Cancer 2008; 44:1345-89; PMID:18280139; http://dx.doi.org/10.1016/j.ejca. 2007.12.015
4. Lopez-Abente G, Ardanaz E, Torrella-Ramos A, Mateos A, Delgado-Sanz C, Chirlaque MD, Colorectal Cancer Working G. Changes in colorectal cancer incidence and mortality trends in Spain. Ann Oncol 2010; 21(Suppl 3):iii76-82; PMID:20427364
5. Gill SR, Pop M, Deboy RT, Eckburg PB, Turnbaugh PJ, Samuel BS, Gordon JI, Relman DA, Fraser-Liggett CM, Nelson KE. Metagenomic analysis of the human distal gut microbiome. Science 2006; 312:1355-9; PMID:16741115; http://dx.doi.org/10.1126/science. 1124234
6. 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; 308:1635-8; PMID:15831718; http://dx. doi.org/10.1126/science.1110591
7. Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, Mende DR, Fernandes GR, Tap J, Bruls T, Batto JM, et al. Enterotypes of the human gut microbiome. Nature 2011; 473:174-80; PMID:21508958; http://dx.doi.org/10.1038/nature09944
8. Qin J, Li R, Raes J, Arumugam M, Burgdorf KS,Manichanh C, Nielsen T, Pons N, Levenez F, Yamada T, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 2010; 464:59-65; PMID:20203603; http://dx.doi.org/10.1038/nature 08821
9. Maccaferri S, Biagi E, Brigidi P. Metagenomics: key to human gut microbiota. Digest Dis 2011; 29:525-30; PMID:22179207; http://dx.doi.org/10.1159/ 000332966
10. Zhao L. The gut microbiota and obesity: from correlation to causality. Nat Rev Microbiol 2013; 11:639-47; PMID:23912213; http://dx.doi.org/10.1038/nrmicro 3089
11. Shen J, Obin MS, Zhao L. The gut microbiota, obesity and insulin resistance. Mol Aspects Med 2013; 34:39-58; PMID:23159341; http://dx.doi.org/10.1016/j. mam.2012.11.001
12. Vaarala O. Human intestinal microbiota and type 1 diabetes. Curr Diab Rep 2013; 13:601-7; PMID:23934614; http://dx.doi.org/10.1007/s11892-013-0409-5
13. Naseer MI, Bibi F, Alqahtani MH, Chaudhary AG, Azhar EI, Kamal MA, Yasir M. Role of gut microbiota in obesity, type 2 diabetes and Alzheimer's disease. CNS Neurol Disord Drug Targets 2014; 13:305-11; PMID:24059313; http://dx.doi.org/10.2174/ 18715273113126660147
14. Tilg H, Moschen AR. Microbiota and diabetes: an evolving relationship. Gut 2014; 63(9):1513-21; PMID:24833634; http://dx.doi.org/10.1136/gutjnl-2014-306928
15. Sears CL, Garrett WS. Microbes, microbiota, and colon cancer. Cell Host Microbe 2014; 15:317-28; PMID:24629338; http://dx.doi.org/10.1016/j.chom. 2014.02.007
16. Rowland IR. The role of the gastrointestinal microbiota in colorectal cancer. Curr Pharm Des 2009; 15:1524-7; PMID:19442169; http://dx.doi.org/10.2174/ 138161209788168191
17. Sofi F, Cesari F, Abbate R, Gensini GF, Casini A. Adherence to Mediterranean diet and health status: meta-analysis. Bmj 2008; 337:a1344; PMID:18786971; http://dx.doi.org/10.1136/bmj. a1344
18. Couto E, Boffetta P, Lagiou P, Ferrari P, Buckland G, Overvad K, Dahm CC, Tjonneland A, Olsen A, Clavel-Chapelon F, et al. Mediterranean dietary pattern and cancer risk in the EPIC cohort. Br J Cancer 2011; 104:1493-9; PMID:21468044; http://dx.doi. org/10.1038/bjc.2011.106
19. Marlow G, Ellett S, Ferguson IR, Zhu S, Karunasinghe N, Jesuthasan AC, Han DY, Fraser AG, Ferguson LR. Transcriptomics to study the effect of a Mediterraneaninspired diet on inflammation in Crohn's disease patients. Hum Genomics 2013; 7:24; PMID:24283712; http://dx.doi.org/10.1186/1479-7364-7-24
20. David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, Ling AV, Devlin AS, Varma Y, Fischbach MA, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 2014; 505:559-63; PMID:24336217; http://dx.doi.org/ 10.1038/nature12820
21. Ahn J, Sinha R, Pei Z, Dominianni C, Wu J, Shi J, Goedert JJ, Hayes RB, Yang L. Human gut microbiome and risk for colorectal cancer. J Natl Cancer Inst 2013; 105:1907-11; PMID:24316595; http://dx.doi. org/10.1093/jnci/djt300
22. Zhu Q, Gao R, Wu W, Qin H. The role of gut microbiota in the pathogenesis of colorectal cancer. Tumour Biol 2013; 34:1285-300; PMID:23397545; http://dx. doi.org/10.1007/s13277-013-0684-4
23. Azcarate-Peril MA, Sikes M, Bruno-Barcena JM. The intestinal microbiota, gastrointestinal environment and colorectal cancer: a putative role for probiotics in prevention of colorectal cancer? Am J Physiol Gastrointest Liver Physiol 2011; 301:G401-24; PMID:21700901; http://dx.doi.org/10.1152/ajpgi.00110.2011
24. Gorbach SL, Thadepalli H. Isolation of Clostridium in human infections: evaluation of 114 cases. J Infect Dis 1975; 131(Suppl):S81-5; PMID:805193; http://dx. doi.org/10.1093/infdis/131.Supplement.S81
25. Klein RS, Recco RA, Catalano MT, Edberg SC, Casey JI, Steigbigel NH. Association of Streptococcus bovis with carcinoma of the colon. N Engl J Med 1977; 297:800-2; PMID:408687; http://dx.doi.org/ 10.1056/NEJM197710132971503
26. Keusch GT. Opportunistic infections in colon carcinoma. Am J Clin Nutr 1974; 27:1481-5; PMID:4611196
27. McCoy AN, Araujo-Perez F, Azcarate-Peril A, Yeh JJ, Sandler RS, Keku TO. Fusobacterium is associated with colorectal adenomas. PLoS One 2013; 8:e53653; PMID:23335968; http://dx.doi.org/10.1371/journal. pone.0053653
28. Kostic AD, Gevers D, Pedamallu CS, Michaud M, Duke F, Earl AM, Ojesina AI, Jung J, Bass AJ, Tabernero J, et al. Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res 2012; 22:292-8; PMID:22009990; http://dx.doi.org/10.1101/gr.126573.111
29. Marchesi JR, Dutilh BE, Hall N, Peters WH, Roelofs R, Boleij A, Tjalsma H. Towards the human colorectal cancer microbiome. PLoS One 2011; 6:e20447; PMID:21647227; http://dx.doi.org/10.1371/journal. pone.0020447
30. Hamer HM, Jonkers D, Venema K, Vanhoutvin S, Troost FJ, Brummer RJ. Review article: the role of butyrate on colonic function. Aliment Pharmacol Ther 2008; 27:104-19; PMID:17973645; http://dx.doi.org/ 10.1111/j.1365-2036.2007.03562.x
31. Kostic AD, Chun E, Robertson L, Glickman JN, Gallini CA, Michaud M, Clancy TE, Chung DC, Lochhead P, Hold GL, et al. Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell Host Microbe 2013; 14:207-15; PMID:23954159; http://dx.doi.org/ 10.1016/j.chom.2013.07.007
32. Brim H, Yooseph S, Zoetendal EG, Lee E, Torralbo M, Laiyemo AO, Shokrani B, Nelson K, Ashktorab H. Microbiome analysis of stool samples from African Americans with colon polyps. PloS One 2013; 8: e81352; PMID:24376500; http://dx.doi.org/10.1371/ journal.pone.0081352
33. Weir TL, Manter DK, Sheflin AM, Barnett BA, Heuberger AL, Ryan EP. Stool microbiome and metabolome differences between colorectal cancer patients and healthy adults. PLoS One 2013; 8:e70803; PMID:23940645; http://dx.doi.org/10.1371/journal. pone.0070803
34. Sobhani I, Tap J, Roudot-Thoraval F, Roperch JP, Letulle S, Langella P, Corthier G, Tran Van Nhieu J, Furet JP. Microbial dysbiosis in colorectal cancer (CRC) patients. PloS One 2011; 6:e16393; PMID:21297998; http://dx.doi.org/10.1371/journal. pone.0016393
35. Wu GD, Chen J, Hoffmann C, Bittinger K, Chen YY, Keilbaugh SA, Bewtra M, Knights D, Walters WA, Knight R, et al. Linking long-term dietary patterns with gut microbial enterotypes. Science 2011; 334:105-8; PMID:21885731; http://dx.doi.org/ 10.1126/science.1208344
36. Ou J, Carbonero F, Zoetendal EG, DeLany JP, Wang M, Newton K, Gaskins HR, O'Keefe SJ. Diet, microbiota, and microbial metabolites in colon cancer risk in rural Africans and African Americans. Am J Clin Nutr 2013; 98:111-20; PMID:23719549; http://dx.doi.org/ 10.3945/ajcn.112.056689
37. O'Keefe SJD, Chung D, Mahmoud N, Sepulveda AR, Manafe M, Arch J, Adada H, van der Merwe T. Why do African Americans get more colon cancer than native Africans? J Nutr 2007; 137:175S-82S; PMID:17182822
38. Langille MG, Zaneveld J, Caporaso JG, McDonald D, Knights D, Reyes JA, Clemente JC, Burkepile DE, Vega Thurber RL, Knight R, et al. Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences. Nat Biotechnol 2013; 31:814-21; PMID:23975157; http://dx.doi.org/ 10.1038/nbt.2676
39. Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, Nielsen T, Pons N, Levenez F, Yamada T, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 2010; 464:59-65; PMID:20203603; http://dx.doi.org/10.1038/ nature08821
40. Dave M, Higgins PD, Middha S, Rioux KP. The human gut microbiome: current knowledge, challenges, and future directions. Transl Res 2012; 160:246-57; PMID:22683238; http://dx.doi.org/10.1016/j. trsl.2012.05.003
41. Keku TO, Dulal S, Deveaux A, Jovov B, Han X. The gastrointestinal microbiota and colorectal cancer. Am J Physiol Gastrointest Liver Physiol 2014; 308(5):G351-G363; http://dx.doi.org/10.1152/ajpgi 00360 2012
42. Chen W, Liu F, Ling Z, Tong X, Xiang C. Human intestinal lumen and mucosa-associated microbiota in patients with colorectal cancer. PloS One 2012; 7: e39743; PMID:22761885; http://dx.doi.org/10.1371/ journal.pone.0039743
43. Shen XJ, Rawls JF, Randall T, Burcal L, Mpande CN, Jenkins N, Jovov B, Abdo Z, Sandler RS, Keku TO. Molecular characterization of mucosal adherent bacteria and associations with colorectal adenomas. Gut Microbes 2010; 1:138-47; PMID:20740058; http:// dx.doi.org/10.4161/gmic.1.3.12360
44. Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG, Contreras M, Magris M, Hidalgo G, Baldassano RN, Anokhin AP, et al. Human gut microbiome viewed across age and geography. Nature 2012; 486:222-7; PMID:22699611
45. De Filippo C, Cavalieri D, Di Paola M, Ramazzotti M, Poullet JB, Massart S, Collini S, Pieraccini G, Lionetti P. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci U S A 2010; 107:14691-6; PMID:20679230; http://dx.doi.org/10.1073/ pnas.1005963107
46. Turroni F, Duranti S, Bottacini F, Guglielmetti S, Van Sinderen D, Ventura M. Bifidobacterium bifidum as an example of a specialized human gut commensal. Front Microbiol 2014; 5:437; PMID:25191315; http://dx.doi.org/10.3389/fmicb.2014.00437
47. Belenguer A, Duncan SH, Calder AG, Holtrop G, Louis P, Lobley GE, Flint HJ. Two routes of metabolic cross-feeding between Bifidobacterium adolescentis and butyrate-producing anaerobes from the human gut. Appl Envir Microbiol 2006; 72:3593-9; PMID:16672507; http://dx.doi.org/10.1128/ AEM.72.5.3593-3599.2006
48. Hill MJ, Drasar BS, Hawksworth G, Aries V, Crowther JS, Williams RE. Bacteria and aetiology of cancer of large bowel. Lancet 1971; 1:95-100; PMID:4099643; http://dx.doi.org/10.1016/S0140-6736(71)90837-3
49. Toprak N, Yagci A, Gulluoglu B, Akin M, Demirkalem P, Celenk T, Soyletir G. A possible role of Bacteroides fragilis enterotoxin in the aetiology of colorectal cancer. Clin Microbiol Infect 2006; 8:782-6; PMID:16842574; http://dx.doi.org/10.1111/j.1469-0691.2006.01494.x
50. Sears CL. Enterotoxigenic Bacteroides fragilis: a rogue among symbiotes. Clin Microbiol Rev 2009; 2:349-69; PMID:19366918; http://dx.doi.org/10.1128/ CMR.00053-08
51. Reynolds TY, Rockwell S, Glazer PM. Genetic instability induced by the tumor microenvironment. Cancer Res 1996; 56:5754-7; PMID:8971187
52. Hirayama A, Kami K, Sugimoto M, Sugawara M, Toki N, Onozuka H, Kinoshita T, Saito N, Ochiai A, Tomita M, et al. Quantitative metabolome profiling of colon and stomach cancer microenvironment by capillary electrophoresis time-of-flight mass spectrometry. Cancer Res 2009; 69:4918-25; PMID:19458066; http://dx.doi.org/10.1158/0008-5472.CAN-08-4806
53. Decker MD. Eikenella corrodens. Infect Control 1986; 7:36-41; PMID:3512467
54. Dewhirst FE, Chen T, Izard J, Paster BJ, Tanner AC, Yu WH, Lakshmanan A, Wade WG. The human oral microbiome. J Bacteriol 2010; 192:5002-17; PMID:20656903; http://dx.doi.org/10.1128/JB.00542-10
55. Fricke WF, Maddox C, Song Y, Bromberg JS. Human microbiota characterization in the course of renal transplantation. Am J Transplant 2014; 14:416-27; PMID:24373208; http://dx.doi.org/10.1111/ajt.12588
56. Lee SH, Fang YC, Luo JP, Kuo HI, Chen HC. Inflammatory pseudotumour associated with chronic persistent Eikenella corrodens infection: a case report and brief review. J Clin Pathol 2003; 56:868-70; PMID: 14600136; http://dx.doi.org/10.1136/jcp.56.11.868
57. Yetimoglu C, Rafeiner P, Engel D, Fournier JY. Spinal infections due to Eikenella corrodens: case report and literature review. Neurochirurgie 2014; 60:197-200; PMID:24874721; http://dx.doi.org/10.1016/j. neuchi.2014.03.002
58. Rivas Castillo FJ, Gomez Martinez JR, Lopez Alvarez F, Garcia Velasco F. Eikenella corrodens: a rare cause of deep neck infection. Acta Otorrinolaringol Esp 2014; pii: S0001-6519(14)00125-3; PMID:25308794; http://dx.doi.org/10.1016
59. Gowda AL, Mease SJ, Dhar Y. Eikenella corrodens septic hip arthritis in a healthy adult treated with arthroscopic irrigation and debridement. Am J Orthop (Belle Mead NJ) 2014; 43:419-21; PMID:25251528
60. Garnier F, Masson G, Bedu A, Masson P, Decroisette E, Guigonis V, Fermeaux V, De Barbentane MC, Denis F, Ploy MC. Maternofetal infections due to Eikenella corrodens. J Med Microbiol 2009; 58:273-5; PMID:19141750; http://dx.doi.org/10.1099/ jmm.0.002568-0
61. Ohkusa T, Okayasu I, Ogihara T, Morita K, Ogawa M, Sato N. Induction of experimental ulcerative colitis by Fusobacterium varium isolated from colonic mucosa of patients with ulcerative colitis. Gut 2003; 52:79-83; PMID:12477765; http://dx.doi.org/10.1136/ gut.52.1.79
62. Warren RL, Freeman DJ, Pleasance S, Watson P, Moore RA, Cochrane K, Allen-Vercoe E, Holt RA. Co-occurrence of anaerobic bacteria in colorectal carcinomas. Microbiome 2013; 1:16; PMID:24450771; http://dx.doi.org/10.1186/2049-2618-1-16
63. Castellarin M, Warren RL, Freeman JD, Dreolini L, Krzywinski M, Strauss J, Barnes R, Watson P, Allen-Vercoe E, Moore RA, et al. Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Res 2012; 22:299-306; PMID:22009989; http://dx.doi.org/10.1101/gr.126516.111
64. Tahara T, Yamamoto E, Suzuki H, Maruyama R, Chung W, Garriga J, Jelinek J, Yamano HO, Sugai T, An B, et al. Fusobacterium in colonic flora and molecular features of colorectal carcinoma. Cancer Res 2014; 74:1311-8; PMID:24385213; http://dx.doi.org/ 10.1158/0008-5472.CAN-13-1865
65. Geng J, Fan H, Tang X, Zhai H, Zhang Z. Diversified pattern of the human colorectal cancer microbiome. Gut Pathog 2013; 5:2; PMID:23497613; http://dx. doi.org/10.1186/1757-4749-5-2
66. Dejea CM, Wick EC, Hechenbleikner EM, White JR, Mark Welch JL, Rossetti BJ, Peterson SN, Snesrud EC, Borisy GG, Lazarev M, et al. Microbiota organization is a distinct feature of proximal colorectal cancers. Proc Natl Acad Sci U S A 2014; 111:18321-6; PMID:25489084; http://dx.doi.org/10.1073/ pnas.1406199111
67. Kostic AD, Gevers D, Pedamallu CS, Michaud M, Duke F, Earl AM, Ojesina AI, Jung J, Bass AJ, Tabernero J, et al. Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res 2011; 146:1489-99; PMID:22009990
68. Chen HM, Yu YN, Wang JL, Lin YW, Kong X, Yang CQ, Yang L, Liu ZJ, Yuan YZ, Liu F, et al. Decreased dietary fiber intake and structural alteration of gut microbiota in patients with advanced colorectal adenoma. Am J Clin Nutr 2013; 97:1044-52; PMID:23553152; http://dx.doi.org/10.3945/ ajcn.112.046607
69. Zackular JP, Rogers MA, Ruffin MTt, Schloss PD. The human gut microbiome as a screening tool for colorectal cancer. Cancer Prev Res (Phila) 2014; 7:1112-21; PMID:25104642; http://dx.doi.org/10.1158/1940-6207.CAPR-14-0129
70. Burns MB, Lynch J, Starr TK, Knights D, Bleckham R. Virulence genes are a signature of the microbiome in the colorectal tumor microenvironment. 2014; http:// dx.doi.org/10.1101/009431
71. Dutilh BE, Backus L, van Hijum SA, Tjalsma H. Screening metatranscriptomes for toxin genes as functional drivers of human colorectal cancer. Best Pract Res Clin Gastroenterol 2013; 27:85-99; PMID:23768555; http://dx.doi.org/10.1016/j. bpg.2013.03.008
72. Devine AA, Gonzalez A, Speck KE, Knight R, Helmrath M, Lund PK, Azcarate-Peril MA. Impact of ileocecal resection and concomitant antibiotics on the microbiome of the murine jejunum and colon. PloS One 2013; 8:e73140; PMID:24015295; http://dx.doi. org/10.1371/journal.pone.0073140
73. Edwards U, Rogall T, Blocker H, Emde M, Bottger EC. Isolation and direct complete nucleotide determination of entire genes. Characterization of a gene coding for 16S ribosomal RNA. Nucleic Acids Res 1989; 17:7843-53; PMID:2798131; http://dx.doi.org/ 10.1093/nar/17.19.7843
74. Fierer N, Hamady M, Lauber CL, Knight R. The influence of sex, handedness, and washing on the diversity of hand surface bacteria. Proc Natl Acad Sci U S A 2008; 105:17994-9; PMID:19004758; http://dx.doi.org/ 10.1073/pnas.0807920105
75. Caporaso JG, Kuczynski J, Stombaugh J, Bittinger K, Bushman FD, Costello EK, Fierer N, Pena AG, Goodrich JK, Gordon JI, et al. QIIME allows analysis of high-throughput community sequencing data. Nat Methods 2010; 7:335-6; PMID:20383131; http://dx. doi.org/10.1038/nmeth.f.303
76. Reeder J, Knight R. Rapidly denoising pyrosequencing amplicon reads by exploiting rank-abundance distributions. Nat Methods 2010; 7:668-9; PMID:20805793; http://dx.doi.org/10.1038/nmeth0910-668b
77. Edgar RC. Search and clustering orders of magnitude faster than BLAST. Bioinformatics 2010; 26:2460-1; PMID:20709691; http://dx.doi.org/10.1093/ bioinformatics/btq461
78. Price MN, Dehal PS, Arkin AP. FastTree 2-approximately maximum-likelihood trees for large alignments. PLoS One 2010; 5:e9490; PMID:20224823; http://dx. doi.org/10.1371/journal.pone.0009490
79. Lozupone C, Hamady M, Knight R. UniFrac-an online tool for comparing microbial community diversity in a phylogenetic context. BMC Bioinformatics 2006; 7:371; PMID:16893466; http://dx.doi.org/ 10.1186/1471-2105-7-371
80. Abubucker S, Segata N, Goll J, Schubert AM, Izard J, Cantarel BL, Rodriguez-Mueller B, Zucker J, Thiagarajan M, Henrissat B, et al. Metabolic reconstruction for metagenomic data and its application to the human microbiome. PLoS Comput Biol 2012; 8:e1002358