From meta-omics to causality: Experimental models for human microbiome research

Microbiome

Volumn 1, Issue 1, 2013, Pages

  Fritz, Joëlle V ^a   Desai, Mahesh S ^a   Shah, Pranjul ^a   Schneider, Jochen G ^a,b   Wilmes, Paul ^a  

^a UNIVERSITY OF LUXEMBOURG   (Luxembourg)

^b SAARLAND UNIVERSITY   (Germany)

Author keywords

Causality; Diet; Disease; Dysbiosis; Ex vivo model; Host microbe interactions; Human microbiome; Hypothesis testing; In silico model; In vitro model; In vivo model; Microfluidics

Indexed keywords

IMMUNOGLOBULIN A; PROBIOTIC AGENT;

BACTERIAL COLONIZATION; BACTERIAL VIRULENCE; BACTERIUM ADHERENCE; BACTEROIDES FRAGILIS; CALORIC INTAKE; CLOSTRIDIUM SPOROGENES; DYSBIOSIS; GENE EXPRESSION; HOST PATHOGEN INTERACTION; HUMAN; MICROBIAL COMMUNITY; MICROBIOME; MICROFLUIDICS; NONHUMAN; PRIORITY JOURNAL; REVIEW;

ANIMALIA;

EID: 84904890211     PISSN: None     EISSN: 20492618     Source Type: Journal    
DOI: 10.1186/2049-2618-1-14     Document Type: Review

References (146)

1. Luckey TD. Introduction to intestinal microecology. Am J Clin Nutr 1972, 25:1292-1294.
2. Peterson J, Garges S, Giovanni M, McInnes P, Wang L, Schloss JA, Bonazzi V, McEwen JE, Wetterstrand KA, Deal C, Baker CC, Di Francesco V, Howcroft TK, Karp RW, Lunsford RD, Wellington CR, Belachew T, Wright M, Giblin C, David H, Mills M, Salomon R, Mullins C, Akolkar B, Begg L, Davis C, Grandison L, Humble M, Khalsa J, Little AR. The NIH human microbiome project. Genome Res 2009, 19:2317-2323. 2792171, 19819907.
3. Markowitz VM, Chen I-M A, Palaniappan K, Chu K, Szeto E, Grechkin Y, Ratner A, Anderson I, Lykidis A, Mavromatis K, Ivanova NN, Kyrpides NC. The integrated microbial genomes system: an expanding comparative analysis resource. Nucleic Acids Res 2010, 38:D382-D390. 10.1093/nar/gkp887, 2808961, 19864254.
4. 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 J-M, Hansen T, Le Paslier D, Linneberg A, Nielsen HB, Pelletier E, Renault P. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 2010, 464:59-65. 10.1038/nature08821, 20203603.
5. Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, Mende DR, Fernandes GR, Tap J, Bruls T, Batto J-M, 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. Enterotypes of the human gut microbiome. Nature 2011, 473:174-180. 10.1038/nature09944, 21508958.
6. Bäckhed 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. 10.1073/pnas.0407076101, 524219, 15505215.
7. Gill SR, Pop M, Deboy RT, Eckburg PB, Turnbaugh PJ, Samuel BS, Gordon JI, Relman D, Fraser-Liggett CM, Nelson KE. Metagenomic analysis of the human distal gut microbiome. Science 2006, 312:1355-1359. 10.1126/science.1124234, 3027896, 16741115.
8. Lathrop SK, Bloom SM, Rao SM, Nutsch K, Lio C-W, Santacruz N, Peterson D, Stappenbeck TS, Hsieh CS. Peripheral education of the immune system by colonic commensal microbiota. Nature 2011, 478:250-254. 10.1038/nature10434, 3192908, 21937990.
9. Olszak T, An D, Zeissig S, Vera MP, Richter J, Franke A, Glickman JN, Siebert R, Baron RM, Kasper DL, Blumberg RS. Microbial exposure during early life has persistent effects on natural killer T cell function. Science 2012, 336:489-493. 10.1126/science.1219328, 3437652, 22442383.
10. Hooper LV, Macpherson AJ. Immune adaptations that maintain homeostasis with the intestinal microbiota. Nat Rev Immunol 2010, 10:159-169. 10.1038/nri2710, 20182457.
11. Van Wey AS, Cookson AL, Roy NC, McNabb WC, Soboleva TK, Shorten PR. Bacterial biofilms associated with food particles in the human large bowel. Mol Nutr Food Res 2011, 55:969-978. 10.1002/mnfr.201000589, 21638777.
12. Leitch ECM, Walker AW, Duncan SH, Holtrop G, Flint HJ. Selective colonization of insoluble substrates by human faecal bacteria. Environ Microbiol 2007, 9:667-679. 10.1111/j.1462-2920.2006.01186.x, 17298367.
13. Ze X, Duncan SH, Louis P, Flint HJ. Ruminococcus bromii is a keystone species for the degradation of resistant starch in the human colon. ISME J 2012, 6:1535-1543. 10.1038/ismej.2012.4, 22343308.
14. Flint HJ, Scott KP, Louis P, Duncan SH. The role of the gut microbiota in nutrition and health. Nat Rev Gastroenterol Hepatol 2012, 9:577-589. 10.1038/nrgastro.2012.156, 22945443.
15. 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. 10.1111/j.1365-2672.2007.03322.x, 17448155.
16. Louis P, Young P, Holtrop G, Flint HJ. Diversity of human colonic butyrate-producing bacteria revealed by analysis of the butyryl-CoA:acetate CoA-transferase gene. Environ Microbiol 2010, 12:304-314. 10.1111/j.1462-2920.2009.02066.x, 19807780.
17. Louis P, Flint HJ. Diversity, metabolism and microbial ecology of butyrate-producing bacteria from the human large intestine. FEMS Microbiol Lett 2009, 294:1-8. 10.1111/j.1574-6968.2009.01514.x, 19222573.
18. Stappenbeck TS, Hooper LV, Gordon JI. Developmental regulation of intestinal angiogenesis by indigenous microbes via Paneth cells. Proc Natl Acad Sci USA 2002, 99:15451-15455. 10.1073/pnas.202604299, 137737, 12432102.
19. Reinhardt C, Bergentall M, Greiner TU, Schaffner F, Ostergren-Lundén G, Petersen LC, Ruf W, Bäckhed F. Tissue factor and PAR1 promote microbiota-induced intestinal vascular remodelling. Nature 2012, 483:627-631. 10.1038/nature10893, 22407318.
20. Turner ML, Healey GD, Sheldon IM. Immunity and inflammation in the uterus. Reprod Domest Anim 2012, 47(Suppl 4):402-409.
21. Nakamura YK, Omaye ST. Metabolic diseases and pro- and prebiotics: mechanistic insights. Nutr Metab 2012, 9:60.
22. Pflughoeft KJ, Versalovic J. Human microbiome in health and disease. Annual Review of Pathology 2012, 7:99-122. 10.1146/annurev-pathol-011811-132421, 21910623.
23. Savage DC. Microbial ecology of the gastrointestinal tract. Ann Rev Microbiol 1977, 31:107-133.
24. Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, Gill SR, Nelson KE, Relman D. Diversity of the human intestinal microbial flora. Science 2005, 308:1635-1638. 10.1126/science.1110591, 1395357, 15831718.
25. Tap J, Mondot S, Levenez F, Pelletier E, Caron C, Furet J-P, Ugarte E, Muñoz-Tamayo R, Paslier DLE, Nalin R, Dore J, Leclerc M. Towards the human intestinal microbiota phylogenetic core. Environ Microbiol 2009, 11:2574-2584. 10.1111/j.1462-2920.2009.01982.x, 19601958.
26. Walker AW, Ince J, Duncan SH, Webster LM, Holtrop G, Ze X, Brown D, Stares MD, Scott P, Bergerat A, Louis P, McIntosh F, Johnstone AM, Lobley GE, Parkhill J, Flint HJ. Dominant and diet-responsive groups of bacteria within the human colonic microbiota. ISME J 2011, 5:220-230. 10.1038/ismej.2010.118, 3105703,3105703, 20686513.
27. Suau A, Bonnet R, Sutren M, Gibson GR, Collins MD, Doré J, Bonnet GIS, Dore J. Direct analysis of genes encoding 16S rRNA from complex communities reveals many novel molecular species within the human Gut direct analysis of genes encoding 16S rRNA from complex communities reveals many novel molecular species within the human Gut. Appl Environ Microbiol 1999, 65:4799-4807. 91647, 10543789.
28. Hold GL, Pryde SE, Russell VJ, Furrie E, Flint HJ. Assessment of microbial diversity in human colonic samples by 16S rDNA sequence analysis. FEMS Microbiol Ecol 2002, 39:33-39. 10.1111/j.1574-6941.2002.tb00904.x, 19709182.
29. Schloissnig S, Arumugam M, Sunagawa S, Mitreva M, Tap J, Zhu A, Waller A, Mende DR, Kultima JR, Martin J, Kota K, Sunyaev SR, Weinstock GM, Bork P. Genomic variation landscape of the human gut microbiome. Nature 2013, 493:45-50.
30. Human Microbiome Project Consortium Structure, function and diversity of the healthy human microbiome. Nature 2012, 486:207-214. 10.1038/nature11234, 3564958, 22699609, Human Microbiome Project Consortium.
31. Jansson J, Willing B, Lucio M, Fekete A, Dicksved J, Halfvarson J, Tysk C, Schmitt-Kopplin P. Metabolomics reveals metabolic biomarkers of Crohn's disease. PLoS One 2009, 4:e6386. 10.1371/journal.pone.0006386, 2713417, 19636438.
32. Verberkmoes NC, Russell AL, Shah M, Godzik A, Rosenquist M, Halfvarson J, Lefsrud MG, Apajalahti J, Tysk C, Hettich RL, Jansson JK. Shotgun metaproteomics of the human distal gut microbiota. ISME J 2009, 3:179-189. 10.1038/ismej.2008.108, 18971961.
33. Gosalbes MJ, Durbán A, Pignatelli M, Abellan JJ, Jiménez-Hernández N, Pérez-Cobas AE, Latorre A, Moya A. Metatranscriptomic approach to analyze the functional human gut microbiota. PLoS One 2011, 6:e17447. 10.1371/journal.pone.0017447, 3050895, 21408168.
34. Roume H, El Muller E, Cordes T, Renaut J, Hiller K, Wilmes P. A biomolecular isolation framework for eco-systems biology. ISME J 2013, 7:110-121. 10.1038/ismej.2012.72, 3526178, 22763648.
35. Wikoff WR, Anfora AT, Liu J, Schultz PG, Lesley S, Peters EC, Siuzdak G. Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proc Natl Acad Sci USA 2009, 106:3698-3703. 10.1073/pnas.0812874106, 2656143, 19234110.
36. Velagapudi VR, Hezaveh R, Reigstad CS, Gopalacharyulu P, Yetukuri L, Islam S, Felin J, Perkins R, Borén J, Oresic M, Bäckhed F. The gut microbiota modulates host energy and lipid metabolism in mice. J Lipid Res 2010, 51:1101-1112. 10.1194/jlr.M002774, 2853437, 20040631.
37. Costello EK, Lauber CL, Hamady M, Fierer N, Gordon JI, Knight R. Bacterial community variation in human body habitats across space and time. Science 2009, 326:1694-1697. 10.1126/science.1177486, 3602444, 19892944.
38. Maurice CF, Haiser HJ, Turnbaugh PJ. Xenobiotics shape the physiology and gene expression of the active human gut microbiome. Cell 2013, 152:39-50. 10.1016/j.cell.2012.10.052, 23332745.
39. Trexler PC, Hon D, Orcutt RP. Development of Gnotobiotics and contamination control in laboratory animal science introduction: nomenclature 1999, Memphis, TN: American Association for Laboratory Animal Science, 50 Years of Laboratory Animal Science. American association for laboratory animal science, book chapter sixteen 121-128. http://www.aalas.org/association/about.aspx.
40. Lundell A-C, Björnsson V, Ljung A, Ceder M, Johansen S, Lindhagen G, Törnhage C-J, Adlerberth I, Wold AE, Rudin A. Infant B cell memory differentiation and early gut bacterial colonization. J Immunol 2012, 188:4315-4322. 10.4049/jimmunol.1103223, 22490441.
41. Cilieborg MS, Boye M, Sangild PT. Bacterial colonization and gut development in preterm neonates. Early Hum Dev 2012, 88(Suppl 1):S41-S49.
42. Garrett WS, Lord GM, Punit S, Lugo-Villarino G, Mazmanian SK, Ito S, Glickman JN, Glimcher LH. Communicable ulcerative colitis induced by T-bet deficiency in the innate immune system. Cell 2007, 131:33-45. 10.1016/j.cell.2007.08.017, 2169385, 17923086.
43. Elinav E, Strowig T, Kau AL, Henao-Mejia J, Thaiss C, Booth CJ, Peaper DR, Bertin J, Eisenbarth SC, Gordon JI, Flavell R. NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis. Cell 2011, 145:745-757. 10.1016/j.cell.2011.04.022, 3140910, 21565393.
44. Kim HJ, Huh D, Hamilton G, Ingber DE. Human gut-on-a-chip inhabited by microbial flora that experiences intestinal peristalsis-like motions and flow. Lab Chip 2012, 12:2165-2174. 10.1039/c2lc40074j, 22434367.
45. Goldsmith JR, Jobin C. Think small: zebrafish as a model system of human pathology. J Biomed Biotechnol 2012, 2012:817341. 3371824, 22701308.
46. Patton EE, Zon LI. The art and design of genetic screens: zebrafish. Nat Rev Genet 2001, 2:956-966. 10.1038/35103567, 11733748.
47. Meeker ND, Trede NS. Immunology and zebrafish: spawning new models of human disease. Dev Comp Immunol 2008, 32:745-757. 10.1016/j.dci.2007.11.011, 18222541.
48. Danilova N, Steiner L. B cells develop in the zebrafish pancreas. Proc Natl Acad Sci USA 2002, 99:13711-13716. 10.1073/pnas.212515999, 129751, 12370418.
49. Ma B, Da L, Na J, Copeland NG. Mouse models of human disease. Part II: recent progress and future directions. Genes Dev 1997, 11:11-43. 10.1101/gad.11.1.11, 9000048.
50. Mestas J, Hughes CCW. Of mice and not men: differences between mouse and human immunology. J Immunol 2004, 172:2731-2738.
51. Ley RE, Bäckhed F, Turnbaugh P, Lozupone C, Knight RD, Gordon JI. Obesity alters gut microbial ecology. Proc Natl Acad Sci USA 2005, 102:11070-11075. 10.1073/pnas.0504978102, 1176910, 16033867.
52. Patterson JK, Lei XG, Miller DD. The pig as an experimental model for elucidating the mechanisms governing dietary influence on mineral absorption. Exp Biol Med (Maywood) 2008, 233:651-664.
53. Rawls JF, Samuel BS, Gordon JI. Gnotobiotic zebrafish reveal evolutionarily conserved responses to the gut microbiota. Proc Natl Acad Sci USA 2004, 101:4596-4601. 10.1073/pnas.0400706101, 384792, 15070763.
54. Rawls JF, Mahowald M, Ley RE, Gordon JI. Reciprocal gut microbiota transplants from zebrafish and mice to germ-free recipients reveal host habitat selection. Cell 2006, 127:423-433. 10.1016/j.cell.2006.08.043, 17055441.
55. Kibe R, Sakamoto M, Yokota H, Aiba Y, Koga Y, Benno Y, Ishikawa H. Movement and fixation of intestinal microbiota after administration of human feces to germfree mice movement and fixation of intestinal microbiota after administration of human feces to germfree mice. Appl Environ Microbiol 2005, 71:3171-3178. 10.1128/AEM.71.6.3171-3178.2005, 1151853, 15933018.
56. Turnbaugh PJ, Ridaura VK, Faith JJ, Rey FE, Gordon JI. The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice. Sci Transl Med 2009, 1:6ra14. 10.1126/scitranslmed.3000322, 2894525, 20368178.
57. Macpherson AJ, Harris NL. Interactions between commensal intestinal bacteria and the immune system. Nat Rev Immunol 2004, 4:478-485. 10.1038/nri1373, 15173836.
58. Umesaki Y, Setoyama H, Matsumoto S, Okada Y. Expansion of alpha beta T-cell receptor-bearing intestinal intraepithelial lymphocytes after microbial colonization in germ-free mice and its independence from thymus. Immunology 1993, 79:32-37. 1422052, 8509140.
59. Helgeland L, Vaage JT, Rolstad B, Midtvedt T, Brandtzaeg P. Microbial colonization influences composition and T-cell receptor V beta repertoire of intraepithelial lymphocytes in rat intestine. Immunology 1996, 89:494-501. 10.1046/j.1365-2567.1996.d01-783.x, 1456593, 9014812.
60. Smith K, McCoy KD, Macpherson AJ. Use of axenic animals in studying the adaptation of mammals to their commensal intestinal microbiota. Semin Immunol 2007, 19:59-69. 10.1016/j.smim.2006.10.002, 17118672.
61. Atarashi K, Tanoue T, Shima T, Imaoka A, Kuwahara T, Momose Y, Cheng G, Yamasaki S, Saito T, Ohba Y, Taniguchi T, Takeda K, Hori S, Ivanov II, Umesaki Y, Itoh K, Honda K. Induction of colonic regulatory T cells by indigenous Clostridium species. Science 2011, 331:337-341. 10.1126/science.1198469, 21205640.
62. Ivanov II, Atarashi K, Manel N, Brodie EL, Shima T, Karaoz U, Wei D, Goldfarb KC, Santee C, Lynch SV, Tanoue T, Imaoka A, Itoh K, Takeda K, Umesaki Y, Honda K, Littman DR. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 2009, 139:485-498. 10.1016/j.cell.2009.09.033, 2796826, 19836068.
63. Gaboriau-Routhiau V, Rakotobe S, Lécuyer 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. 10.1016/j.immuni.2009.08.020, 19833089.
64. Savage DC, Siegel JE, Snellen JE, Whitt DD. Transit time of epithelial cells in the small intestines of germfree mice and transit time of epithelial cells in the small intestines of germfree mice and ex-germfree mice associated with indigenous microorganisms. Appl Environ Microbiol 1981, 42:996-1001. 244145, 7198427.
65. Khoury KA, Floch MH, Hersh T. Small intestinal mucosal cell proliferation and bacterial flora in the conventionalization of the germfree mouse. J Exp Med 1969, 130:659-670. 10.1084/jem.130.3.659, 2138714, 4896909.
66. 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, 444:1027-1031. 10.1038/nature05414, 17183312.
67. Turnbaugh PJ, Bäckhed F, Fulton L, Gordon JI. Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe 2008, 3:213-223. 10.1016/j.chom.2008.02.015, 18407065.
68. Vijay-Kumar M, Aitken JD, Carvalho F, Cullender TC, Mwangi S, Srinivasan S, Sitaraman SV, Knight R, Ley RE, Gewirtz AT. Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5. Science 2010, 328:228-231. 10.1126/science.1179721, 20203013.
69. Nanthakumar NN, Dai D, Meng D, Chaudry N, Newburg DS, Walker WA. Regulation of intestinal ontogeny: effect of glucocorticoids and luminal microbes on galactosyltransferase and trehalase induction in mice. Glycobiology 2005, 15:221-232.
70. Hooper LV, Wong MH, Thelin A, Hansson L, Falk PG, Gordon JI. Molecular analysis of commensal host-microbial relationships in the intestine. Science 2001, 291:881-884. 10.1126/science.291.5505.881, 11157169.
71. Hirayama K, Itoht K, Takahashit E, Shinozaki K, Sawasaki T. Composition of faecal microbiota and metabolism of faecal bacteria of pig-flora-associated (PFA) mice. Microb Ecol Health Dis 1996, 9:199-206.
72. Claus SP, Tsang TM, Wang Y, Cloarec O, Skordi E, Martin F-P, Rezzi S, Ross A, Kochhar S, Holmes E, Nicholson JK. Systemic multicompartmental effects of the gut microbiome on mouse metabolic phenotypes. Mol Syst Biol 2008, 4:219. 2583082, 18854818.
73. Welling GW, Groen G, Tuinte JH, Koopman JP, Kennis HM. Biochemical effects on germ-free mice of association with several strains of anaerobic bacteria. J Gen Microbiol 1980, 117:57-63.
74. Manichanh C, Reeder J, Gibert P, Varela E, Llopis M, Antolin M, Guigo R, Knight R, Guarner F. Reshaping the gut microbiome with bacterial transplantation and antibiotic intake. Genome Res 2010, 20:1411-1419. 10.1101/gr.107987.110, 2945190, 20736229.
75. Meinl W, Sczesny S, Brigelius-Flohé R, Blaut M, Glatt H. Impact of gut microbiota on intestinal and hepatic levels of phase 2 xenobiotic-metabolizing enzymes in the rat. Drug Metab Dispo 2009, 37:1179-1186.
76. Swann JR, Want EJ, Geier FM, Spagou K, Wilson ID, Sidaway JE, Nicholson JK, Holmes E. Systemic gut microbial modulation of bile acid metabolism in host tissue compartments. Proc Natl Acad Sci USA 2011, 108(Suppl):4523-4530. 10.1073/pnas.1006734107, 3063584, 20837534.
77. Nicholls AW, Mortishire-smith RJ, Nicholson JK. Urinary metabolite variation in acclimatizing germ-free rats. Chem Res Toxicol 2003, 16:1395-1404. 10.1021/tx0340293, 14615964.
78. Chin SF, Storkson JM, Liu W, Albright KJ, Pariza MW. Conjugated linoleic acid (9,11- and 10,12-octadecadienoic acid) is produced in conventional but not germ-free rats fed linoleic acid. J Nutr 1994, 124:694-701.
79. Morton KC, Wang CY. Enhanced macromolecular binding of N-[4-(5-nitro-2-furyl)-2-thiazolyl]- formamide in germfree versus conventional rats. Cancer Res 1983, 43:3628-3632.
80. Ducluzeau R, Raibaud P, Dickinson AB, Sacquet E, Mocquot G. Hydrolysis of urea in vitro and in vivo, in the cecum of gnotobiotic rats, by different bacterial strains isolated from the digestive tract of conventional rats. C R Acad Sci Hebd Seances Acad Sci D 1966, 262:944-947.
81. Wostmann BS, Bruckner-Kardoss E. Oxidation-reduction potentials in cecal contents of germfree and conventional rats. Proc Soc Exp Biol Med 1966, 121:1111-1114.
82. Gérard P, Béguet F, Lepercq P, Rigottier-Gois L, Rochet V, Andrieux C, Juste C. Gnotobiotic rats harboring human intestinal microbiota as a model for studying cholesterol-to-coprostanol conversion. FEMS Microbiol Ecol 2004, 47:337-343. 10.1016/S0168-6496(03)00285-X, 19712322.
83. Bowey E, Adlercreutz H, Rowland I. Metabolism of isoflavones and lignans by the gut microflora: a study in germ-free and human flora associated rats. Food Chem Toxicol 2003, 41:631-636. 10.1016/S0278-6915(02)00324-1, 12659715.
84. Szentkuti L, Riedesel H, Enss ML, Gaertner K, Von Engelhardt W. Pre-epithelial mucus layer in the colon of conventional and germ-free rats. Histochem J 1990, 22:491-497. 10.1007/BF01007234, 1702088.
85. Meslin JC, Fontaine N, Andrieux C. Variation of mucin distribution in the rat intestine, caecum and colon: effect of the bacterial flora. Comp Biochem Physiol A Mol Integr Physiol 1999, 123:235-239. 10.1016/S1095-6433(99)00056-2, 10501018.
86. Sharma R, Schumacher U. Morphometric analysis of intestinal mucins under different dietary conditions and gut flora in rats. Dig Dis Sci 1995, 40:2532-2539. 10.1007/BF02220438, 8536508.
87. Helgeland L, Dissen E, Dai K-Z, Midtvedt T, Brandtzaeg P, Vaage JT. Microbial colonization induces oligoclonal expansions of intraepithelial CD8 T cells in the gut. Eur J Immunol 2004, 34:3389-3400. 10.1002/eji.200425122, 15517613.
88. Banasaz M, Norin E, Holma R, Midtvedt T. Increased enterocyte production in gnotobiotic rats mono-associated with Lactobacillus rhamnosus GG. Appl Environ Microbiol 2002, 68:3031-3034. 10.1128/AEM.68.6.3031-3034.2002, 123962, 12039764.
89. Leser TD, Amenuvor JZ, Jensen TK, Lindecrona RH, Boye M, Møller K. Culture-independent analysis of gut bacteria: the Pig gastrointestinal tract microbiota revisited culture-independent analysis of gut bacteria: the Pig gastrointestinal tract microbiota revisited. Appl Environ Microbiol 2002, 68:673-690. 10.1128/AEM.68.2.673-690.2002, 126712, 11823207.
90. Guo X, Xia X, Tang R, Zhou J, Zhao H, Wang K. Development of a real-time PCR method for Firmicutes and Bacteroidetes in faeces and its application to quantify intestinal population of obese and lean pigs. Lett Appl Microbiol 2008, 47:367-373. 10.1111/j.1472-765X.2008.02408.x, 19146523.
91. Chowdhury SR, King DE, Willing BP, Band MR, Beever JE, Lane AB, Loor JJ, Marini JC, Rund L, Schook LB, Van Kessel AG, Gaskins HR. Transcriptome profiling of the small intestinal epithelium in germfree versus conventional piglets. BMC Genomics 2007, 8:215. 10.1186/1471-2164-8-215, 1949829, 17615075.
92. Pang X, Hua X, Yang Q, Ding D, Che C, Cui L, Jia W, Bucheli P, Zhao L. Inter-species transplantation of gut microbiota from human to pigs. ISME J 2007, 1:156-162. 10.1038/ismej.2007.23, 18043625.
93. Bates JM, Mittge E, Kuhlman J, Baden KN, Cheesman SE, Guillemin K. Distinct signals from the microbiota promote different aspects of zebrafish gut differentiation. Dev Biol 2006, 297:374-386. 10.1016/j.ydbio.2006.05.006, 16781702.
94. Treiner E, Duban L, Bahram S, Radosavljevic M, Wanner V, Tilloy F, Affaticati P, Gilfillan S, Lantz O. Selection of evolutionarily conserved mucosal-associated invariant T cells by MR1. Nature 2003, 422:164-169. 10.1038/nature01433, 12634786.
95. Bäckhed F, Manchester JK, Semenkovich CF, Gordon JI. Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc Natl Acad Sci USA 2007, 104:979-984. 10.1073/pnas.0605374104, 1764762, 17210919.
96. Caballero-Franco C, Keller K, De Simone C, Chadee K. The VSL#3 probiotic formula induces mucin gene expression and secretion in colonic epithelial cells. Am J Physiol Gastrointest Liver Physiol 2007, 292:G315-G322.
97. Gootenberg DB, Turnbaugh PJ. Companion animals symposium: humanized animal models of the microbiome. J Anim Sci 2011, 89:1531-1537. 10.2527/jas.2010-3371, 20833767.
98. Yin Y, Wang Y, Zhu L, Liu W, Liao N, Jiang M, Zhu B, Yu HD, Xiang C, Wang X. Comparative analysis of the distribution of segmented filamentous bacteria in humans, mice and chickens. ISME J 2013, 7:615-621. 10.1038/ismej.2012.128, 23151642.
99. Chung H, Pamp SJ, Hill J, Surana NK, Edelman SM, Troy EB, Reading NC, Villablanca EJ, Wang S, Mora JR, Umesaki Y, Mathis D, Benoist C, Relman D, Kasper DL. Gut immune maturation depends on colonization with a host-specific microbiota. Cell 2012, 149:1578-1593. 10.1016/j.cell.2012.04.037, 22726443.
100. Round JL, Mazmanian SK. Inducible Foxp3 + regulatory T-cell development by a commensal bacterium of the intestinal microbiota. Proc Natl Acad Sci USA 2010, 107:12204-12209. 10.1073/pnas.0909122107, 2901479, 20566854.
101. Hapfelmeier S, Lawson ME, Slack E, Kirundi JK, Stoel M, Heikenwalder M, Cahenzli J, Velykoredko Y, Balmer ML, Endt K, Geuking MB, Curtiss R, McCoy KD, Macpherson AJ. Reversible microbial colonization of germ-free mice reveals the dynamics of IgA immune responses. Science 2010, 328:1705-1709. 10.1126/science.1188454, 20576892.
102. Tremaroli V, Bäckhed F. Functional interactions between the gut microbiota and host metabolism. Nature 2012, 489:242-249. 10.1038/nature11552, 22972297.
103. Legrand N, Ploss A, Balling R, Becker PD, Borsotti C, Brezillon N, Debarry J, De Jong Y, Deng H, Di Santo JP, Eisenbarth S, Eynon E, Flavell R, Guzman C, Huntington ND, Kremsdorf D, Manns MP, Manz MG, Mention J-J, Ott M, Rathinam C, Rice CM, Rongvaux A, Stevens S, Spits H, Strick-Marchand H, Takizawa H, Van Lent AU, Wang C, Weijer K. Humanized mice for modeling human infectious disease: challenges, progress, and outlook. Cell Host Microbe 2009, 6:5-9. 10.1016/j.chom.2009.06.006, 19616761.
104. Gimeno R, Weijer K, Voordouw A, Uittenbogaart CH, Legrand N, Alves NL, Wijnands E, Blom B, Spits H. Monitoring the effect of gene silencing by RNA interference in human CD34+ cells injected into newborn RAG2-/- gammac-/- mice: functional inactivation of p53 in developing T cells. Blood 2004, 104:3886-3893. 10.1182/blood-2004-02-0656, 15319293.
105. Ito M, Hiramatsu H, Kobayashi K, Suzue K, Kawahata M, Hioki K, Ueyama Y. NOD / SCID / gamma null c mouse: an excellent recipient mouse model for engraftment of human cells. Blood 2002, 100:3175-3182. 10.1182/blood-2001-12-0207, 12384415.
106. Melkus MW, Estes JD, Padgett-Thomas A, Gatlin J, Denton PW, Othieno F, Wege AK, Haase AT, Garcia JV. Humanized mice mount specific adaptive and innate immune responses to EBV and TSST-1. Nat Med 2006, 12:1316-1322. 10.1038/nm1431, 17057712.
107. Traggiai E, Chicha L, Mazzucchelli L, Bronz L, Piffaretti J-C, Lanzavecchia A, Manz MG. Development of a human adaptive immune system in cord blood cell-transplanted mice. Science 2004, 304:104-107. 10.1126/science.1093933, 15064419.
108. Kovatcheva-Datchary P, Zoetendal EG, Venema K, De Vos WM, Smidt H. Tools for the tract: understanding the functionality of the gastrointestinal tract. Therap Adv Gastroenterol 2009, 2:9-22. 10.1177/1756283X09337646, 3002528, 21180550.
109. Molly K, Vande Woestyne M, Verstraete W. Development of a 5-step multi-chamber reactor as a simulation of the human intestinal microbial ecosystem. Appl Microbiol Biotechnol 1993, 39:254-258.
110. Van den Abbeele P, Roos S, Eeckhaut V, MacKenzie D, Derde M, Verstraete W, Marzorati M, Possemiers S, Vanhoecke B, Van Immerseel F, Van de Wiele T. Incorporating a mucosal environment in a dynamic gut model results in a more representative colonization by lactobacilli. Microb Biotechnol 2012, 5:106-115. 10.1111/j.1751-7915.2011.00308.x, 21989255.
111. Minekus M, Marteau P, Havenaar R, Huis INTVELDJHJ. A multicompartmental dynamic computer-controlled model simulating the stomach and small intestine. ATLA 1995, 23:197-209.
112. Minekus M, Smeets-Peeters M, Bernalier A, Marol-Bonnin S, Havenaar R, Marteau P, Alric M, Fonty G, Huis in't Veld JH. A computer-controlled system to simulate conditions of the large intestine with peristaltic mixing, water absorption and absorption of fermentation products. Appl Microbiol Biotechnol 1999, 53:108-114. 10.1007/s002530051622, 10645630.
113. Macfarlane GT, Gibson GR, Cummings JH. Comparison of fermentation reactions in different regions of the human colon. J Appl Bacteriol 1992, 72:57-64.
114. Molly K, Vande Woestyne M, De Smet I, Verstraete W. Validation of the simulator of the human intestinal microbial ecosystem (SHIME) reactor using microorganism-associated activities. Microb Ecol Health Dis 1994, 7:191-200.
115. Vermeiren J, Van den Abbeele P, Laukens D, Vigsnaes LK, De Vos M, Boon N, Van de Wiele T. Decreased colonization of fecal Clostridium coccoides/Eubacterium rectale species from ulcerative colitis patients in an in vitro dynamic gut model with mucin environment. FEMS Microbiol Ecol 2012, 79:685-696. 10.1111/j.1574-6941.2011.01252.x, 22092917.
116. Bahrami B, Child MW, Macfarlane S, Macfarlane GT. Adherence and cytokine induction in Caco-2 cells by bacterial populations from a three-stage continuous-culture model of the large intestine. Appl Environ Microbiol 2011, 77:2934-2942. 10.1128/AEM.02244-10, 3126424, 21378047.
117. Bahrami B, Macfarlane S, Macfarlane GT. Induction of cytokine formation by human intestinal bacteria in gut epithelial cell lines. J Appl Microbiol 2011, 110:353-363. 10.1111/j.1365-2672.2010.04889.x, 21070518.
118. Payne AN, Zihler A, Chassard C, Lacroix C. Advances and perspectives in in vitro human gut fermentation modeling. Trends Biotechnol 2012, 30:17-25. 10.1016/j.tibtech.2011.06.011, 21764163.
119. Rose W, McGowin CL, Spagnuolo RA, Eaves-Pyles TD, Popov VL, Pyles RB. Commensal bacteria modulate innate immune responses of vaginal epithelial cell multilayer cultures. PLoS One 2012, 7:e32728. 10.1371/journal.pone.0032728, 3296736, 22412914.
120. Fukuda S, Toh H, Hase K, Oshima K, Nakanishi Y, Yoshimura K, Tobe T, Clarke JM, Topping DL, Suzuki T, Taylor TD, Itoh K, Kikuchi J, Morita H, Hattori M, Ohno H. Bifidobacteria can protect from enteropathogenic infection through production of acetate. Nature 2011, 469:543-547. 10.1038/nature09646, 21270894.
121. Buess M, Nuyten DSA, Hastie T, Nielsen T, Pesich R, Brown PO. Characterization of heterotypic interaction effects in vitro to deconvolute global gene expression profiles in cancer. Genome Biol 2007, 8:R191. 10.1186/gb-2007-8-9-r191, 2375029, 17868458.
122. Bhatia SN, Balis UJ, Yarmush ML, Toner M. Probing heterotypic cell interactions: hepatocyte function in microfabricated co-cultures. J Biomater Sci Polym Ed 1998, 9:1137-1160. 10.1163/156856298X00695, 9860177.
123. Shah P, Vedarethinam I, Kwasny D, Andresen L, Dimaki M, Skov S, Svendsen WE. Microfluidic bioreactors for culture of non-adherent cells. Sensors Actuators B: Chemical 2011, 156:1002-1008.
124. Meyvantsson I, Beebe DJ. Cell culture models in microfluidic systems. Annu Rev Anal Chem (Palo Alto Calif) 2008, 1:423-449.
125. Pasirayi G, Auger V, M Scott S, K S M Rahman P, Islam M, O'Hare L, Ali Z. Microfluidic bioreactors for cell culturing: a review. Micro Nanosystemse 2011, 3:137-160.
126. Huh D, Hamilton GA, Ingber DE. From 3D cell culture to organs-on-chips. Trends Cell Biol 2011, 21:745-754. 10.1016/j.tcb.2011.09.005, 22033488.
127. Turnbaugh PJ, Ley RE, Hamady M, Fraser-Liggett CM, Knight R, Gordon JI. The human microbiome project. Nature 2007, 449:804-810. 10.1038/nature06244, 17943116.
128. Kim J, Hegde M, Jayaraman A. Co-culture of epithelial cells and bacteria for investigating host-pathogen interactions. Lab Chip 2010, 10:43-50. 10.1039/b911367c, 20024049.
129. Park J, Kerner A, Burns MA, Lin XN. Microdroplet-enabled highly parallel co-cultivation of microbial communities. PLoS One 2011, 6:e17019. 10.1371/journal.pone.0017019, 3045426, 21364881.
130. McBain AJ. Chapter 4: In vitro biofilm models: an overview. Adv Appl Microbiol 2009, 69:99-132.
131. Coenye T, Nelis HJ. In vitro and in vivo model systems to study microbial biofilm formation. J Microbiol Methods 2010, 83:89-105. 10.1016/j.mimet.2010.08.018, 20816706.
132. Saleh-Lakha S, Trevors JT. Perspective: microfluidic applications in microbiology. J Microbiol Methods 2010, 82:108-111. 10.1016/j.mimet.2010.03.022, 20363265.
133. Bhatia SN, Balis UJ, Yarmush ML, Toner M. Effect of cell-cell interactions in preservation of cellular phenotype: cocultivation of hepatocytes and nonparenchymal cells. FASEB J 1999, 13:1883-1900.
134. Stybayeva G, Zhu H, Ramanculov E, Dandekar S, George M, Revzin A. Micropatterned co-cultures of T-lymphocytes and epithelial cells as a model of mucosal immune system. Biochem Biophys Res Commun 2009, 380:575-580. 10.1016/j.bbrc.2009.01.164, 2659419, 19285003.
135. Lindén SK, Driessen KM, McGuckin MA. Improved in vitro model systems for gastrointestinal infection by choice of cell line, pH, microaerobic conditions, and optimization of culture conditions. Helicobacter 2007, 12:341-353. 10.1111/j.1523-5378.2007.00509.x, 17669108.
136. Pellicanò A, Leone I, Imeneo M, Amorosi A, Luzza F. Co-culture of human gastric endoscopic biopsies with Helicobacter pylori: a simple method for studying early phases of bacteria-host interaction. J Microbiol Methods 2008, 75:346-349. 10.1016/j.mimet.2008.05.025, 18588923.
137. Subbiahdoss G, Kuijer R, Grijpma DW, Van der Mei HC, Busscher HJ. Microbial biofilm growth vs. tissue integration: " the race for the surface" experimentally studied. Acta Biomater 2009, 5:1399-1404. 10.1016/j.actbio.2008.12.011, 19158003.
138. Saldarriaga Fernández IC, Busscher HJ, Metzger SW, Grainger DW, Van der Mei HC. Competitive time- and density-dependent adhesion of staphylococci and osteoblasts on crosslinked poly(ethylene glycol)-based polymer coatings in co-culture flow chambers. Biomaterials 2011, 32:979-984. 10.1016/j.biomaterials.2010.10.011, 20980049.
139. Skolimowski M, Abeille F, Nielsen MW, Lopacinska JD, Molin S, Taboryski R, Sternberg C, Dufva M, Geschke O, Emnéus J. Microfluidic model of cystic fibrosis bronchi. Fifteenth International Conference on Miniaturized Systems for Chemistry and Life Science, Seattle, Washington, USA (2011), Curran Associates, Inc 2012, 3:2. 118.
140. Grivel J-C, Margolis L. Use of human tissue explants to study human infectious agents. Nat Protoc 2009, 4:256-269. 10.1038/nprot.2008.245, 3427853, 19197269.
141. Tsilingiri K, Barbosa T, Penna G, Caprioli F, Sonzogni A, Viale G, Rescigno M. Probiotic and postbiotic activity in health and disease: comparison on a novel polarised ex-vivo organ culture model. Gut 2012, 61:1007-1015. 10.1136/gutjnl-2011-300971, 22301383.
142. Palsson BO. Systems biology: properties of reconstructed networks 2006, 334. Cambridge, UK: Cambridge Univ Press.
143. Thiele I, Heinken A, Fleming RMT. A systems biology approach to studying the role of microbes in human health. Curr Opin Biotechnol 2013, 24:4-12. 10.1016/j.copbio.2012.10.001, 23102866.
144. Zengler K, Palsson BO. A road map for the development of community systems (CoSy) biology. Nat Rev Microbiol 2012, 10:366-372.
145. Heinken A, Sahoo S, Fleming RMT, Thiele I. Systems-level characterization of a host-microbe metabolic symbiosis in the mammalian gut. Gut microbes 2013, 4:28-40. 10.4161/gmic.22370, 3555882, 23022739.
146. Ma MG, Lindén SK, Sutton P, Florin TH. Mucin dynamics and enteric pathogens. Nat Rev Microbiol 2011, 9:265-278. 10.1038/nrmicro2538, 21407243.