Download PDF
Semin Liver Dis 2016; 36(04): 306-311
DOI: 10.1055/s-0036-1594008
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Studying the Microbiome: “Omics” Made Accessible

Paul W. O'Toole
1   Department of Microbiology, APC Microbiome Institute, University College Cork, Cork, Ireland
,
Burkhardt Flemer
1   Department of Microbiology, APC Microbiome Institute, University College Cork, Cork, Ireland
› Author Affiliations
Further Information

Publication History

Publication Date:
20 December 2016 (online)

    Permissions and Reprints

Abstract

The term microbiome refers to the collection of microbes or microbial genes in a specified location or clinical sample. Identifying micro-organisms has historically relied upon bacteriological culture, which is time consuming and difficult to effectively implement. The recent adaptation of culture-independent techniques for profiling microbial communities, allied with next-generation massively parallel DNA sequencing, allows clinician scientists to determine the entire microbial content of a specimen to a forensic level of detail within 48 hours. The technology is still young, and the main thrust of current efforts is to identify how changes in the microbiome covary with a variety of syndromes and diseases, and to determine if these changes are causative or consequential. Regardless of the outcome of these investigations, it is already apparent that the gut microbiome is a useful biomarker for intestinal and extraintestinal disease. In this review, the authors summarize the main concepts in microbiome analysis, and prospects for the microbiome's clinical deployment.

Keywords

microbiome - microbiota - intestinal disease
 

  • References

  • 1 Gullett JC, Nolte FS. Quantitative nucleic acid amplification methods for viral infections. Clin Chem 2015; 61 (1) 72-78
    CrossrefPubMedGoogle Scholar
  • 2 Browne HP, Forster SC, Anonye BO , et al. Culturing of ‘unculturable’ human microbiota reveals novel taxa and extensive sporulation. Nature 2016; 533 (7604) 543-546
    CrossrefPubMedGoogle Scholar
  • 3 Walker AW, Duncan SH, Louis P, Flint HJ. Phylogeny, culturing, and metagenomics of the human gut microbiota. Trends Microbiol 2014; 22 (5) 267-274
    CrossrefPubMedGoogle Scholar
  • 4 Rigottier-Gois L, Bourhis AG, Gramet G, Rochet V, Doré J. Fluorescent hybridisation combined with flow cytometry and hybridisation of total RNA to analyse the composition of microbial communities in human faeces using 16S rRNA probes. FEMS Microbiol Ecol 2003; 43 (2) 237-245
    CrossrefPubMedGoogle Scholar
  • 5 Mueller S, Saunier K, Hanisch C , et al. Differences in fecal microbiota in different European study populations in relation to age, gender, and country: a cross-sectional study. Appl Environ Microbiol 2006; 72 (2) 1027-1033
    CrossrefPubMedGoogle Scholar
  • 6 Zoetendal EG, Rajilic-Stojanovic M, de Vos WM. High-throughput diversity and functionality analysis of the gastrointestinal tract microbiota. Gut 2008; 57 (11) 1605-1615
    CrossrefPubMedGoogle Scholar
  • 7 Kassinen A, Krogius-Kurikka L, Mäkivuokko H , et al. The fecal microbiota of irritable bowel syndrome patients differs significantly from that of healthy subjects. Gastroenterology 2007; 133 (1) 24-33
    CrossrefPubMedGoogle Scholar
  • 8 Manichanh C, Rigottier-Gois L, Bonnaud E , et al. Reduced diversity of faecal microbiota in Crohn's disease revealed by a metagenomic approach. Gut 2006; 55 (2) 205-211
    CrossrefPubMedGoogle Scholar
  • 9 Consortium HMP ; Human Microbiome Project Consortium. A framework for human microbiome research. Nature 2012; 486 (7402) 215-221
    CrossrefPubMedGoogle Scholar
  • 10 Qin J, Li R, Raes J , et al; MetaHIT Consortium. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 2010; 464 (7285) 59-65
    CrossrefPubMedGoogle Scholar
  • 11 Faust K, Sathirapongsasuti JF, Izard J , et al. Microbial co-occurrence relationships in the human microbiome. PLOS Comput Biol 2012; 8 (7) e1002606
    CrossrefPubMedGoogle Scholar
  • 12 Gevers D, Knight R, Petrosino JF , et al. The Human Microbiome Project: a community resource for the healthy human microbiome. PLoS Biol 2012; 10 (8) e1001377
    CrossrefPubMedGoogle Scholar
  • 13 Lloyd-Price J, Abu-Ali G, Huttenhower C. The healthy human microbiome. Genome Med 2016; 8 (1) 51
    CrossrefPubMedGoogle Scholar
  • 14 Arrieta MC, Stiemsma LT, Amenyogbe N, Brown EM, Finlay B. The intestinal microbiome in early life: health and disease. Front Immunol 2014; 5: 427
    PubMedGoogle Scholar
  • 15 Cho I, Blaser MJ. The human microbiome: at the interface of health and disease. Nat Rev Genet 2012; 13 (4) 260-270
    CrossrefPubMedGoogle Scholar
  • 16 Buttó LF, Schaubeck M, Haller D. Mechanisms of microbe-host interaction in Crohn's disease: dysbiosis vs. pathobiont selection. Front Immunol 2015; 6: 555
    PubMedGoogle Scholar
  • 17 Darfeuille-Michaud A, Boudeau J, Bulois P , et al. High prevalence of adherent-invasive Escherichia coli associated with ileal mucosa in Crohn's disease. Gastroenterology 2004; 127 (2) 412-421
    CrossrefPubMedGoogle Scholar
  • 18 Manichanh C, Borruel N, Casellas F, Guarner F. The gut microbiota in IBD. Nat Rev Gastroenterol Hepatol 2012; 9 (10) 599-608
    CrossrefPubMedGoogle Scholar
  • 19 Quévrain E, Maubert MA, Michon C , et al. Identification of an anti-inflammatory protein from Faecalibacterium prausnitzii, a commensal bacterium deficient in Crohn's disease. Gut 2016; 65 (3) 415-425
    CrossrefPubMedGoogle Scholar
  • 20 Salonen A, de Vos WM, Palva A. Gastrointestinal microbiota in irritable bowel syndrome: present state and perspectives. Microbiology 2010; 156 (Pt 11) 3205-3215
    CrossrefPubMedGoogle Scholar
  • 21 Jeffery IB, Quigley EM, Öhman L, Simrén M, O'Toole PW. The microbiota link to irritable bowel syndrome: an emerging story. Gut Microbes 2012; 3 (6) 572-576
    CrossrefPubMedGoogle Scholar
  • 22 Hayes PA, Fraher MH, Quigley EM. Irritable bowel syndrome: the role of food in pathogenesis and management. Gastroenterol Hepatol (N Y) 2014; 10 (3) 164-174
    PubMedGoogle Scholar
  • 23 Qin N, Yang F, Li A , et al. Alterations of the human gut microbiome in liver cirrhosis. Nature 2014; 513 (7516) 59-64
    CrossrefPubMedGoogle Scholar
  • 24 Quigley EM, Monsour HP. The gut microbiota and nonalcoholic fatty liver disease. Semin Liver Dis 2015; 35 (3) 262-269
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Llopis M, Cassard AM, Wrzosek L , et al. Intestinal microbiota contributes to individual susceptibility to alcoholic liver disease. Gut 2016; 65 (5) 830-839
    CrossrefPubMedGoogle Scholar
  • 26 Vrieze A, Van Nood E, Holleman F , et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology 2012; 143 (4) 913-6 .e7
    CrossrefPubMedGoogle Scholar
  • 27 Hungate RE. Symposium: selected topics in microbial ecology. I. Microbial ecology of the rumen. Bacteriol Rev 1960; 24 (4) 353-364
    PubMedGoogle Scholar
  • 28 Savage DC. Microbial ecology of the gastrointestinal tract. Annu Rev Microbiol 1977; 31: 107-133
    CrossrefPubMedGoogle Scholar
  • 29 Sender R, Fuchs S, Milo R. Revised estimates for the number of human and bacteria cells in the body. PLoS Biol 2016; 14 (8) e1002533
    CrossrefPubMedGoogle Scholar
  • 30 Woese CR, Fox GE. Phylogenetic structure of the prokaryotic domain: the primary kingdoms. Proc Natl Acad Sci U S A 1977; 74 (11) 5088-5090
    CrossrefPubMedGoogle Scholar
  • 31 Medlin L, Elwood HJ, Stickel S, Sogin ML. The characterization of enzymatically amplified eukaryotic 16S-like rRNA-coding regions. Gene 1988; 71 (2) 491-499
    CrossrefPubMedGoogle Scholar
  • 32 Venter JC, Remington K, Heidelberg JF , et al. Environmental genome shotgun sequencing of the Sargasso Sea. Science 2004; 304 (5667) 66-74
    CrossrefPubMedGoogle Scholar
  • 33 Eckburg PB, Bik EM, Bernstein CN , et al. Diversity of the human intestinal microbial flora. Science 2005; 308 (5728) 1635-1638
    CrossrefPubMedGoogle Scholar
  • 34 Schrader C, Schielke A, Ellerbroek L, Johne R. PCR inhibitors - occurrence, properties and removal. J Appl Microbiol 2012; 113 (5) 1014-1026
    CrossrefPubMedGoogle Scholar
  • 35 Gohl DM, Vangay P, Garbe J , et al. Systematic improvement of amplicon marker gene methods for increased accuracy in microbiome studies. Nat Biotechnol 2016; 34 (9) 942-949
    CrossrefPubMedGoogle Scholar
  • 36 Klindworth A, Pruesse E, Schweer T , et al. Evaluation of general 16S ribosomal RNA gene PCR primers for classical and next-generation sequencing-based diversity studies. Nucleic Acids Res 2013; 41 (1) e1
    CrossrefPubMedGoogle Scholar
  • 37 Flemer B, Lynch DB, Brown JM , et al. Tumour-associated and non-tumour-associated microbiota in colorectal cancer. Gut 2016; gutjnl-2015-309595
    PubMedGoogle Scholar
  • 38 Lu H, Ren Z, Li A , et al. Deep sequencing reveals microbiota dysbiosis of tongue coat in patients with liver carcinoma. Sci Rep 2016; 6: 33142
    CrossrefPubMedGoogle Scholar
  • 39 Baxter NT, Ruffin MT, Rogers MAM, Schloss PD. Microbiota-based model improves the sensitivity of fecal immunochemical test for detecting colonic lesions. Genome Med 2016; 8 (1) 37
    CrossrefPubMedGoogle Scholar
  • 40 Amaral-Zettler LA, McCliment EA, Ducklow HW, Huse SM. A method for studying protistan diversity using massively parallel sequencing of V9 hypervariable regions of small-subunit ribosomal RNA genes. PLoS One 2009; 4 (7) e6372
    CrossrefPubMedGoogle Scholar
  • 41 Singer E, Bushnell B, Coleman-Derr D , et al. High-resolution phylogenetic microbial community profiling. ISME J 2016; 10 (8) 2020-2032
    CrossrefPubMedGoogle Scholar
  • 42 Caporaso JG, Kuczynski J, Stombaugh J , et al. QIIME allows analysis of high-throughput community sequencing data. Nat Methods 2010; 7 (5) 335-336
    CrossrefPubMedGoogle Scholar
  • 43 Schloss PD, Westcott SL, Ryabin T , et al. Introducing mothur: open-source, platform-independent, community-supported software for describing and comparing microbial communities. Appl Environ Microbiol 2009; 75 (23) 7537-7541
    CrossrefPubMedGoogle Scholar
  • 44 Edgar RC. Search and clustering orders of magnitude faster than BLAST. Bioinformatics 2010; 26 (19) 2460-2461
    CrossrefPubMedGoogle Scholar
  • 45 Team RCR. A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2013
    Google Scholar
  • 46 Kanehisa M, Goto S, Sato Y, Kawashima M, Furumichi M, Tanabe M. Data, information, knowledge and principle: back to metabolism in KEGG. Nucleic Acids Res 2014; 42 (Database issue) D199-D205
    CrossrefPubMedGoogle Scholar
  • 47 Ashburner M, Ball CA, Blake JA , et al; The Gene Ontology Consortium. Gene ontology: tool for the unification of biology. Nat Genet 2000; 25 (1) 25-29
    CrossrefPubMedGoogle Scholar
  • 48 Consortium HMP ; Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature 2012; 486 (7402) 207-214
    CrossrefPubMedGoogle Scholar
  • 49 Zeller G, Tap J, Voigt AY , et al. Potential of fecal microbiota for early-stage detection of colorectal cancer. Mol Syst Biol 2014; 10: 766
    CrossrefPubMedGoogle Scholar
  • 50 Castellarin M, Warren RL, Freeman JD , et al. Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Res 2012; 22 (2) 299-306
    CrossrefPubMedGoogle Scholar
  • 51 Franzosa EA, Morgan XC, Segata N , et al. Relating the metatranscriptome and metagenome of the human gut. Proc Natl Acad Sci U S A 2014; 111 (22) E2329-E2338
    CrossrefPubMedGoogle Scholar
  • 52 Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 2006; 444 (7122) 1027-1031
    CrossrefPubMedGoogle Scholar
  • 53 Muccioli GG, Naslain D, Bäckhed F , et al. The endocannabinoid system links gut microbiota to adipogenesis. Mol Syst Biol 2010; 6: 392
    CrossrefPubMedGoogle Scholar
  • 54 Perry RJ, Peng L, Barry NA , et al. Acetate mediates a microbiome-brain-β-cell axis to promote metabolic syndrome. Nature 2016; 534 (7606) 213-217
    CrossrefPubMedGoogle Scholar
  • 55 Sayin SI, Wahlström A, Felin J , et al. Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist. Cell Metab 2013; 17 (2) 225-235
    CrossrefPubMedGoogle Scholar
  • 56 Le Chatelier E, Nielsen T, Qin J , et al; MetaHIT consortium. Richness of human gut microbiome correlates with metabolic markers. Nature 2013; 500 (7464) 541-546
    CrossrefPubMedGoogle Scholar
  • 57 Zeevi D, Korem T, Zmora N , et al. Personalized nutrition by prediction of glycemic responses. Cell 2015; 163 (5) 1079-1094
    CrossrefPubMedGoogle Scholar
  • 58 Rajilić-Stojanović M, Biagi E, Heilig HG , et al. Global and deep molecular analysis of microbiota signatures in fecal samples from patients with irritable bowel syndrome. Gastroenterology 2011; 141 (5) 1792-1801
    CrossrefPubMedGoogle Scholar
  • 59 Carroll IM, Ringel-Kulka T, Keku TO , et al. Molecular analysis of the luminal- and mucosal-associated intestinal microbiota in diarrhea-predominant irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol 2011; 301 (5) G799-G807
    CrossrefPubMedGoogle Scholar
  • 60 Jeffery IB, O'Toole PW, Öhman L , et al. An irritable bowel syndrome subtype defined by species-specific alterations in faecal microbiota. Gut 2012; 61 (7) 997-1006
    CrossrefPubMedGoogle Scholar
  • 61 Sears CL, Garrett WS. Microbes, microbiota, and colon cancer. Cell Host Microbe 2014; 15 (3) 317-328
    CrossrefPubMedGoogle Scholar
  • 62 Flynn KJ, Baxter NT, Schloss PD. Metabolic and community synergy of oral bacteria in colorectal cancer. mSphere 2016; 1 (3) 102-116
    PubMedGoogle Scholar
  • 63 Vipperla K, O'Keefe SJ. Diet, microbiota, and dysbiosis: a ‘recipe’ for colorectal cancer. Food Funct 2016; 7 (4) 1731-1740
    CrossrefPubMedGoogle Scholar
  • 64 Yu J, Feng Q, Wong SH , et al. Metagenomic analysis of faecal microbiome as a tool towards targeted non-invasive biomarkers for colorectal cancer. Gut 2015; gutjnl-2015-309800
    PubMedGoogle Scholar
  • 65 Zackular JP, Rogers MA, Ruffin IV MT, Schloss PD. The human gut microbiome as a screening tool for colorectal cancer. Cancer Prev Res (Phila) 2014; 7 (11) 1112-1121
    CrossrefPubMedGoogle Scholar