Human biology can only be fully assessed by combining an analysis of both the host and its surrounding environment. As a part of the environment, the human gastrointestinal tract hosts more than 100 trillion bacteria making up the gut microbiota. The human host provides a nutrient-rich environment while the microbiota provides indispensable functions that humans cannot exert themselves. Shifts in the bacterial makeup of the human gut microbiota have been associated with disorders such as inflammatory bowel disease (IBD), irritable bowel syndrome and obesity. However, since most bacteria inhabiting our gut are not cultivable to date, until recently little was known about their individual functions. Metagenomics, i.e. the analysis of the collective genomes present in a defined ecosystem, gives insight into these specific functions. The first extensive catalogue of the intestinal metagenome outnumbers the size of the human genome by a factor of 150. Recently, 3 distinct ‘types’ of gut composition within the human population have been highlighted. These so-called ‘enterotypes’ are characterized by the dominant genera (Bacteroides, Prevotella and Ruminococcus) and their co-occurring phylogenetic groups. In accordance with the previously described impact of nutritional behavior (diet, probiotics and prebiotics) on specific bacterial populations, an association has been observed between long-term dietary habits and enterotypes. This recent discovery, i.e. that belonging to one or the other enterotype might be modulated by the diet opens up new perspectives in the fields of IBD, nutrition and therapeutic strategies.

Keywords:
Microbiota, Crohn’s disease, Ulcerative colitis, Nutrition, Enterotypes
1.
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.
2.
Tap J, Mondot S, Levenez F, Pelletier E, Caron C, Furet JP, Ugarte E, Munoz-Tamayo R, Paslier DL, Nalin R, Dore J, Leclerc M: Towards the human intestinal microbiota phylogenetic core. Environ Microbiol 2009;11:2574–2584.
3.
Dethlefsen L, Eckburg PB, Bik EM, Relman DA: Assembly of the human intestinal microbiota. Trends Ecol Evol 2006;21:517–523.
4.
Ley RE, Hamady M, Lozupone C, Turnbaugh PJ, Ramey RR, Bircher JS, Schlegel ML, Tucker TA, Schrenzel MD, Knight R, Gordon JI: Evolution of mammals and their gut microbes. Science 2008;320:1647–1651.
5.
Bocci V: The neglected organ: bacterial flora has a crucial immunostimulatory role. Perspect Biol Med 1992;35:251–260.
6.
Backhed F, Ley RE, Sonnenburg JL, Peterson DA, Gordon JI: Host-bacterial mutualism in the human intestine. Science 2005;307:1915–1920.
7.
Cummings JH: Microbial digestion of complex carbohydrates in man. Proc Nutr Soc 1984;43:35–44.
8.
Hooper LV, Midtvedt T, Gordon JI: How host-microbial interactions shape the nutrient environment of the mammalian intestine. Annu Rev Nutr 2002;22:283–307.
9.
Kelly D, Campbell JI, King TP, Grant G, Jansson EA, Coutts AG, Pettersson S, Conway S: Commensal anaerobic gut bacteria attenuate inflammation by regulating nuclear-cytoplasmic shuttling of PPAR-gamma and RelA. Nat Immunol 2004;5:104–112.
10.
Willing BP, Van Kessel AG: Enterocyte proliferation and apoptosis in the caudal small intestine is influenced by the composition of colonizing commensal bacteria in the neonatal gnotobiotic pig. J Anim Sci 2007;85:3256–3266.
11.
Berg RD: The indigenous gastrointestinal microflora. Trends Microbiol 1996;4:430–435.
12.
Savage DC: Microorganisms associated with epithelial surfaces and stability of the indigenous gastrointestinal microflora. Nahrung 1987;31:383–395.
13.
Edwards DP: The roles of tolerance in the evolution, maintenance and breakdown of mutualism. Naturwissenschaften 2009;96:1137–1145.
14.
Gaboriau-Routhiau V, Rakotobe S, Lecuyer E, Mulder I, Lan A, Bridonneau C, Rochet V, Pisi A, De Paepe M, Brandi G, Eberl G, Snel J, Kelly D, Cerf-Bensussan N: The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. Immunity 2009;31:677–689.
15.
Neish AS: Microbes in gastrointestinal health and disease. Gastroenterology 2009;136:65–80.
16.
Round JL, Mazmanian SK: The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol 2009;9:313–323.
17.
Mondot S, Kang S, Furet JP, Aguirre de Carcer D, McSweeney C, Morrison M, Marteau P, Dore J, Leclerc M: Highlighting new phylogenetic specificities of Crohn’s disease microbiota. Inflamm Bowel Dis 2011;17:185–192.
18.
Backhed F, Ding H, Wang T, Hooper LV, Koh GY, Nagy A, Semenkovich CF, Gordon JI: The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci USA 2004;101:15718–15723.
19.
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.
20.
Lepage P, Hasler R, Spehlmann ME, Rehman A, Zvirbliene A, Begun A, Ott S, Kupcinskas L, Dore J, Raedler A, Schreiber S: Twin study indicates loss of interaction between microbiota and mucosa of patients with ulcerative colitis. Gastroenterology 2011;141:227–236.
21.
Ley RE, Backhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI: Obesity alters gut microbial ecology. Proc Natl Acad Sci USA 2005;102:11070–11075.
22.
Ley RE, Turnbaugh PJ, Klein S, Gordon JI: Microbial ecology: human gut microbes associated with obesity. Nature 2006;444:1022–1023.
23.
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.
24.
Marteau P, Lepage P, Mangin I, Suau A, Dore J, Pochart P, Seksik P: Review article: gut flora and inflammatory bowel disease. Aliment Pharmacol Ther 2004;20(suppl 4):18–23.
25.
Seksik P, Sokol H, Lepage P, Vasquez N, Manichanh C, Mangin I, Pochart P, Dore J, Marteau P: Review article: the role of bacteria in onset and perpetuation of inflammatory bowel disease. Aliment Pharmacol Ther 2006;24(suppl 3):11–18.
26.
Sartor RB: Intestinal microflora in human and experimental inflammatory bowel disease. Curr Opin Gastroenterol 2001;17:324–330.
27.
Nagalingam NA, Lynch SV: Role of the microbiota in inflammatory bowel diseases. Inflamm Bowel Dis 2012;18;968–984.
28.
Tamboli CP, Neut C, Desreumaux P, Colombel JF: Dysbiosis as a prerequisite for ibd. Gut 2004;53:1057.
29.
Lahti L, Salojarvi J, Nikkila J, Salonen A, De Vos W: Meta-analysis of human gut microbiota: Community composition and health associations F1000 Posters. 2011;2:1147.
30.
Ott SJ, Schreiber S: Reduced microbial diversity in inflammatory bowel diseases. Gut 2006;55:1207.
31.
Sokol H, Pigneur B, Watterlot L, Lakhdari O, Bermudez-Humaran LG, Gratadoux JJ, Blugeon S, Bridonneau C, Furet JP, Corthier G, Grangette C, Vasquez N, Pochart P, Trugnan G, Thomas G, Blottiere HM, Dore 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.
32.
Sokol H, Seksik P, Furet JP, Firmesse O, Nion-Larmurier I, Beaugerie L, Cosnes J, Corthier G, Marteau P, Dore J: Low counts of Faecalibacterium prausnitzii in colitis microbiota. Inflamm Bowel Dis 2009;15:1183–1189.
33.
Gophna U, Sommerfeld K, Gophna S, Doolittle WF, Veldhuyzen van Zanten SJ: Differences between tissue-associated intestinal microfloras of patients with Crohn’s disease and ulcerative colitis. J Clin Microbiol 2006;44:4136–4141.
34.
Seksik P, Rigottier-Gois L, Gramet G, Sutren M, Pochart P, Marteau P, Jian R, Dore J: Alterations of the dominant faecal bacterial groups in patients with Crohn’s disease of the colon. Gut 2003;52:237–242.
35.
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.
36.
Grossfeld GD, Li YP, DP PL, Carroll PR: Patterns of failure after primary local therapy for prostate cancer and rationale for secondary therapy. Urology 2002;60:57–62;discussion 62–63.
37.
Michail S, Durbin M, Turner D, Griffiths AM, Mack DR, Hyams J, Leleiko N, Kenche H, Stolfi A, Wine E: Alterations in the gut microbiome of children with severe ulcerative colitis. Inflamm Bowel Dis 2011, E-pub ahead of print.
38.
Handelsman J: Metagenomics: application of genomics to uncultured microorganisms. Microbiol Mol Biol Rev 2004;68:669–685.
39.
Lepage P, Leclerc MC, Joossens M, Mondot S, Blottiere HM, Raes J, Ehrlich D, Dore J: A metagenomic insight into our gut’s microbiome. Gut 2012, E-pub ahead of print. PubMed PMID: 22525886.
40.
Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, Nielsen T, Pons N, Levenez F, Yamada T, Mende DR, Li J, Xu J, Li S, Li D, Cao J, Wang B, Liang H, Zheng H, Xie Y, Tap J, Lepage P, Bertalan M, Batto JM, Hansen T, Le Paslier D, Linneberg A, Nielsen HB, Pelletier E, Renault P, Sicheritz-Ponten T, Turner K, Zhu H, Yu C, Jian M, Zhou Y, Li Y, Zhang X, Qin N, Yang H, Wang J, Brunak S, Dore J, Guarner F, Kristiansen K, Pedersen O, Parkhill J, Weissenbach J, Bork P, Ehrlich SD: A human gut microbial gene catalogue established by metagenomic sequencing. Nature 2010;464:59–65.
41.
Chapman-Kiddell CA, Davies PS, Gillen L, Radford-Smith GL: Role of diet in the development of inflammatory bowel disease. Inflamm Bowel Dis 2010;16:137–151.
42.
Burkitt DP: Related disease – related cause? Lancet 1969;2:1229–1231.
43.
Aune D, Chan DS, Lau R, Vieira R, Greenwood DC, Kampman E, Norat T: Dietary fibre, whole grains, and risk of colorectal cancer: systematic review and dose-response meta-analysis of prospective studies. BMJ 2011;343:d6617.
44.
Lattimer JM, Haub MD: Effects of dietary fiber and its components on metabolic health. Nutrients 2010;2:1266–1289.
45.
Venkatraman A, Ramakrishna BS, Shaji RV, Kumar NS, Pulimood A, Patra S: Amelioration of dextran sulfate colitis by butyrate: role of heat shock protein 70 and NF-kappaB. Am J Physiol Gastrointest Liver Physiol 2003;285:G177–G184.
46.
Jowett SL, Seal CJ, Pearce MS, Phillips E, Gregory W, Barton JR, Welfare MR: Influence of dietary factors on the clinical course of ulcerative colitis: a prospective cohort study. Gut 2004;53:1479–1484.
47.
Tilg H, Kaser A: Diet and relapsing ulcerative colitis: take off the meat? Gut 2004;53:1399–1401.
48.
Asakura H, Suzuki K, Kitahora T, Morizane T: Is there a link between food and intestinal microbes and the occurrence of Crohn’s disease and ulcerative colitis? J Gastroenterol Hepatol 2008;23:1794–1801.
49.
Shoda R, Matsueda K, Yamato S, Umeda N: Epidemiologic analysis of Crohn disease in Japan: increased dietary intake of n-6 polyunsaturated fatty acids and animal protein relates to the increased incidence of Crohn disease in Japan. Am J Clin Nutr 1996;63:741–745.
50.
Palmer C, Bik EM, DiGiulio DB, Relman DA, Brown PO: Development of the human infant intestinal microbiota. PLoS Biol 2007;5:e177.
51.
Wang Z, Xiao G, Yao Y, Guo S, Lu K, Sheng Z: The role of bifidobacteria in gut barrier function after thermal injury in rats. J Trauma 2006;61:650–657.
52.
Cani PD, Neyrinck AM, Fava F, Knauf C, Burcelin RG, Tuohy KM, Gibson GR, Delzenne NM: Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia 2007;50:2374–2383.
53.
Joossens M, De Preter V, Ballet V, Verbeke K, Rutgeerts P, Vermeire S: Effect of oligofructose-enriched inulin (OF-IN) on bacterial composition and disease activity of patients with Crohn’s disease: results from a double-blinded randomised controlled trial. Gut 2012;61:958.
54.
Flint HJ, Bayer EA, Rincon MT, Lamed R, White BA: Polysaccharide utilization by gut bacteria: potential for new insights from genomic analysis. Nat Rev Microbiol 2008;6:121–131.
55.
Hughes R, Magee EA, Bingham S: Protein degradation in the large intestine: Relevance to colorectal cancer. Curr Issues Intest Microbiol 2000;1:51–58.
56.
Cummings JH, Macfarlane GT: The control and consequences of bacterial fermentation in the human colon. J Appl Bacteriol 1991;70:443–459.
57.
Gibson SA, McFarlan C, Hay S, MacFarlane GT: Significance of microflora in proteolysis in the colon. Appl Environ Microbiol 1989;55:679–683.
58.
Macfarlane GT, Allison C, Gibson SA, Cummings JH: Contribution of the microflora to proteolysis in the human large intestine. J Appl Bacteriol 1988;64:37–46.
59.
Christl SU, Eisner HD, Dusel G, Kasper H, Scheppach W: Antagonistic effects of sulfide and butyrate on proliferation of colonic mucosa: a potential role for these agents in the pathogenesis of ulcerative colitis. Dig Dis Sci 1996;41:2477–2481.
60.
Roediger WE: Colonic epithelial metabolism in ulcerative colitis. Gut 1993;34:1646.
61.
Roediger WE, Duncan A, Kapaniris O, Millard S: Reducing sulfur compounds of the colon impair colonocyte nutrition: implications for ulcerative colitis. Gastroenterology 1993;104:802–809.
62.
Medani M, Collins D, Docherty NG, Baird AW, O’Connell PR, Winter DC: Emerging role of hydrogen sulfide in colonic physiology and pathophysiology. Inflamm Bowel Dis 2011;17:1620–1625.
63.
Miller TW, Wang EA, Gould S, Stein EV, Kaur S, Lim L, Amarnath S, Fowler DH, Roberts DD: Hydrogen sulfide is an endogenous potentiator of T cell activation. J Biol Chem 2012;287:4211–4221.
64.
Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, Mende DR, Fernandes GR, Tap J, Bruls T, Batto JM, Bertalan M, Borruel N, Casellas F, Fernandez L, Gautier L, Hansen T, Hattori M, Hayashi T, Kleerebezem M, Kurokawa K, Leclerc M, Levenez F, Manichanh C, Nielsen HB, Nielsen T, Pons N, Poulain J, Qin J, Sicheritz-Ponten T, Tims S, Torrents D, Ugarte E, Zoetendal EG, Wang J, Guarner F, Pedersen O, de Vos WM, Brunak S, Doré J, MetaHIT Consortium, Antolín M, Artiguenave F, Blottiere HM, Almeida M, Brechot C, Cara C, Chervaux C, Cultrone A, Delorme C, Denariaz G, Dervyn R, Foerstner KU, Friss C, van de Guchte M, Guedon E, Haimet F, Huber W, van Hylckama-Vlieg J, Jamet A, Juste C, Kaci G, Knol J, Lakhdari O, Layec S, Le Roux K, Maguin E, Mérieux A, Melo Minardi R, M’rini C, Muller J, Oozeer R, Parkhill J, Renault P, Rescigno M, Sanchez N, Sunagawa S, Torrejon A, Turner K, Vandemeulebrouck G, Varela E, Winogradsky Y, Zeller G, Weissenbach J, Ehrlich SD, Bork P: Enterotypes of the human gut microbiome. Nature. 2011 May 12;473:174–80.
65.
Wu GD, Chen J, Hoffmann C, Bittinger K, Chen YY, Keilbaugh SA, Bewtra M, Knights D, Walters WA, Knight R, Sinha R, Gilroy E, Gupta K, Baldassano R, Nessel L, Li H, Bushman FD, Lewis JD: Linking long-term dietary patterns with gut microbial enterotypes. Science 2011;334:105–108.
66.
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 USA 2010;107:14691–14696.
67.
Louis P, Scott KP, Duncan SH, Flint HJ: Understanding the effects of diet on bacterial metabolism in the large intestine. J Appl Microbiol 2007;102:1197–1208.
68.
Martins dos Santos V, Müller M, de Vos WM: Systems biology of the gut: the interplay of food, microbiota and host at the mucosal interface. Curr Opin Biotechnol. 2010 Aug; 21:539–550.
© 2012 S. Karger AG, Basel
2013
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.