The human gut is a complex ecosystem occupied by a diverse microbial community. Modulation of this microbiota impacts health and disease. The definitive way to investigate the impact of dietary intervention on the gut microbiota is a human trial. However, human trials are expensive and can be difficult to control; thus, initial screening is desirable. Utilization of a range of in vitro and in vivo models means that useful information can be gathered prior to the necessity for human intervention. This review discusses the benefits and limitations of these approaches.


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Literature Cited

  1. Alander M, De Smet I, Nollet L, Verstraete W, von Wright A, Mattila-Sandholm T. 1999a. The effect of probiotic strains on the microbiota of the Simulator of the Human Intestinal Microbial Ecosystem (SHIME). Int. J. Food Microbiol. 46:71–79 [Google Scholar]
  2. Alander M, Satokari R, Korpela R, Saxelin M, Vilpponen-Salmela T. et al. 1999b. Persistence of colonization of human colonic mucosa by a probiotic strain, Lactobacillus rhamnosus GG, after oral consumption. Appl. Environ. Microbiol. 65:351–54 [Google Scholar]
  3. Asahara T, Nomoto K, Shimizu K, Watanuki M, Tanaka R. 2001. Increased resistance of mice to Salmonella enterica serovar Typhimurium infection by synbiotic administration of Bifidobacteria and transgalactosylated oligosaccharides. J. Appl. Microbiol. 91:985–96 [Google Scholar]
  4. Bahrami B, Child MW, Macfarlane S, Macfarlane GT. 2011. 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. 77:2934–42 [Google Scholar]
  5. Ballyk M, Dung L, Jones DA. 1998. Effects of random motility on microbial growth and competition in a flow reactor. SIAM J. Appl. Math. 59:573–96 [Google Scholar]
  6. Ballyk M, Smith H. 1999. A model of microbial growth in a plug flow reactor with wall attachment. Math. Biosci. 158:95–126 [Google Scholar]
  7. Ballyk MM, Smith H. 2001. Microbial competition in reactors with wall attachment: a mathematical comparison of chemostat and plug flow models. Microb. Ecol. 41:210–21 [Google Scholar]
  8. Barry J-L, Hoebler C, Macfarlane GT, Macfarlane S, Mathers JC. et al. 1995. Estimation of the fermentability of dietary fibre in vitro: a European interlaboratory study. Br. J. Nutr. 74:303–22 [Google Scholar]
  9. Bartosch S, Woodmansey EJ, Paterson JCM, McMurdo MET, Macfarlane GT. 2005. Microbiological effects of consuming a synbiotic containing Bifidobacterium bifidum, Bifidobacterium lactis and oligofructose in elderly persons, determined by real-time polymerase chain reaction and counting of viable bacteria. Clin. Infect. Dis. 40:28–37 [Google Scholar]
  10. Beards E, Tuohy K, Gibson G. 2010. Bacterial, SCFA and gas profiles of a range of food ingredients following in vitro fermentation by human colonic microbiota. Anaerobe 16:420–25 [Google Scholar]
  11. Berends BR, Urlings HA, Snijders JM, van Knapen F. 1996. Identification and quantification of risk factors in animal management and transport regarding Salmonella spp. in pigs. Int. J. Food Microbiol. 30:37–53 [Google Scholar]
  12. Berner AZ, Fuentes S, Dostal A, Payne AN, Gutierrez PV. et al. 2013. Novel Polyfermentor Intestinal Model (PolyFermS) for controlled ecological studies: validation and effect of pH. PLoS ONE 8:e77772 [Google Scholar]
  13. Bernhardt H, Wellmer A, Zimmermann K, Knoke M. 1995. Growth of Candida albicans in normal and altered faecal flora in the model of continuous flow culture. Mycoses 38:265–70 [Google Scholar]
  14. Bielecka M, Biedrzycka E, Majkowska A. 2002. Selection of probiotics and prebiotics for synbiotics and confirmation of their in vivo effectiveness. Food Res. Int. 35:125–31 [Google Scholar]
  15. Björklund M, Ouwehand AC, Forssten SD, Nikkilä J, Tiihonen K. et al. 2012. Gut microbiota of healthy elderly NSAID users is selectively modified with the administration of Lactobacillus acidophilus NCFM and lactitol. Age 34:987–99 [Google Scholar]
  16. Bouhnik Y, Flourie B, Andrieux C, Bisetti N, Briet F, Rambaud JC. 1996. Effects of Bifidobacterium sp fermented milk ingested with or without inulin on colonic bifidobacteria and enzymatic activities in healthy humans. Eur. J. Clin. Nutr. 50:269–73 [Google Scholar]
  17. Boureau H, Hartmann L, Karjalainen T, Rowland I, Wilkinson MHF. 2000. Models to study colonisation and colonisation resistance. Microb. Ecol. Health D 2:247–58 [Google Scholar]
  18. Burr DH, Sugiyama H, Harvis G. 1982. Susceptibility to enteric botulinum colonization of antibiotic treated adult mice. Infect. Immun. 36:103–6 [Google Scholar]
  19. Cinquin C, Le Blay G, Fliss I, Lacroix C. 2004. Immobilization of infant fecal microbiota and utilization in an in vitro colonic fermentation model. Microb. Ecol. 48:128–38 [Google Scholar]
  20. Cinquin C, Le Blay G, Fliss I, Lacroix C. 2006. New three-stage in vitro model for infant colonic fermentation with immobilized fecal microbiota. FEMS Microbial. Ecol. 57:324–36 [Google Scholar]
  21. Coleman ME, Dreesen DW, Wiegert RG. 1996. A simulation of microbial competition in the human colonic ecosystem. Appl. Environ. Microbiol. 62:3632–39 [Google Scholar]
  22. Cummings JH, Macfarlane GT. 1991. The control and consequences of bacterial fermentation in the human colon. J. Appl. Bacteriol. 70:443–59 [Google Scholar]
  23. de Graaf AA, Maathuis A, de Waard P, Deutz NEP, Dijkema C. et al. 2010. Profiling human gut bacterial metabolism and its kinetics using [U-13C]glucose and NMR. NMR Biomed. 23:2–12 [Google Scholar]
  24. de Graaf AA, Venema K. 2008. Gaining insight into microbial physiology in the large intestine: a special role for stable isotopes. Adv. Microb. Physiol. 53:73–168 [Google Scholar]
  25. de Jong P, Vissers MMM, van der Meer R, Bovee-Oudenhoven IMJ. 2007. In silico model as a tool for interpretation of intestinal infection studies. Appl. Environ. Microbiol. 73:508–15 [Google Scholar]
  26. Franks AH, Harmsen HJM, Raangs GC, Jansen GJ, Schut F, Welling GW. 1998. Variations of bacteria populations in human feces measured by fluorescent in situ hybridization with group-specific 16S rRNA-targeted oligonucleotide probes. Environ. Microbiol. 64:3336–45 [Google Scholar]
  27. Freter R. 1983. Mechanisms that control the microflora in the large intestine. Human Intestinal Microflora in Health and Disease D Hentges 33–54 New York: Academic [Google Scholar]
  28. Gabridge MG. 1974. Parabiotic chamber for organ cultures: improved model. Appl. Microbiol. 28:774–77 [Google Scholar]
  29. Gerritsen J, Smidt H, Rijkers GT, de Vos WM. 2011. Intestinal microbiota in human health and disease: the impact of probiotics. Genes Nutr. 6:209–40 [Google Scholar]
  30. Gibbons DL, Spencer J. 2011. Mouse and human intestinal immunity: same ballpark, different players; different rules, same score. Mucosal Immunol. 4:148–57 [Google Scholar]
  31. Gibson GR, Cummings JH, Macfarlane GT. 1988. Use of a three-stage continuous culture system to study the effect of mucin on dissimilatory sulfate reduction and methanogenesis by mixed populations of human gut bacteria. Appl. Environ. Microbiol. 54:2750–55 [Google Scholar]
  32. Gietl E, Mengerink W, de Slegte J, Gibson G, Rastall R, van den Heuvel E. 2012. Factors involved in the in vitro fermentability of short carbohydrates in static faecal batch cultures. Int. J. Carbohydr. Chem. 2012:197809 [Google Scholar]
  33. Gill SR, Pop M, DeBoy RT, Eckberg PB, Turnbaugh PJ. et al. 2006. Metagenomic analysis of the human distal gut microbiome. Science 312:1355–59 [Google Scholar]
  34. Gmeiner M, Kneifel W, Kulbe KD, Wouters R, De Boever P, Nollet L. et al. 2000. Influence of a synbiotic mixture consisting of Lactobacillus acidophilus 74-2 and a fructooligosaccharide preparation on the microbial ecology sustained in a simulation of the human intestinal microbial ecosystem (SHIME reactor). Appl. Microbiol. Biotechnol. 53:219–23 [Google Scholar]
  35. Gorbach SL, Barza M, Giulaiano M, Jacobus NV. 1988. Colonization resistance of the human intestinal microflora: testing the hypothesis in normal volunteers. Eur. J. Clin. Microbiol. Infect. Dis. 7:98–102 [Google Scholar]
  36. Grant AJ, Woodward J, Maskell DJ. 2006. Development of an ex vivo organ culture model using human gastro-intestinal tissue and Campylobacter jejuni. FEMS Microbiol. Lett. 263:240–43 [Google Scholar]
  37. Grootaert C, Van den Abbeele P, Marzorati M, Broekaert WF, Courtin CM. et al. 2009. Comparison of prebiotic effects of arabinoxylan oligosaccharides and inulin in a simulator of the human intestinal microbial ecosystem. FEMS Microbiol. Ecol. 69:231–42 [Google Scholar]
  38. Gumienna M, Lasik M, Czarnecki Z. 2011. Bioconversion of grape and chokeberry wine polyphenols during simulated gastrointestinal in vitro digestion. Int. J. Food Sci. Nutr. 62:226–33 [Google Scholar]
  39. Hansen SR, Hubbell SP. 1980. Single-nutrient microbial competition: qualitative agreement between experimental and theoretically forecast outcomes. Science 207:1491–93 [Google Scholar]
  40. Hatanaka M, Nakamura Y, Maathuis AJH, Venema K, Murota I, Yamamoto N. 2012. Influence of Bacillus subtilis C-3102 on microbiota in a dynamic in vitro model of the gastrointestinal tract simulating human conditions. Benef. Microbes 3:229–36 [Google Scholar]
  41. Hazenberg MP, Bakker M, Verschoor-Burggraaf A. 1981. Effects of the human intestinal flora on germ-free mice. J. Appl. Bacteriol. 50:95–106 [Google Scholar]
  42. Hicks S, Candy DCA, Phillips AD. 1996. Adhesion of enteroaggressive Escherichia coli to pediatric intestinal mucosa in vitro. Infect. Immun. 64:4751–60 [Google Scholar]
  43. Hobden MR, Martin-Morales A, Guérin-Deremaux L, Wils D, Costabile A. et al. 2013. In vitro fermentation of NUTRIOSE® FB06, a wheat dextrin soluble fibre, in a continuous culture human colonic model system. PLoS ONE 8:e77128 [Google Scholar]
  44. Holzapfel WH, Haberer P, Snel J, Schilinger U, Huis in't Veld JHJ. 1998. Overview of gut flora and probiotics. Int. J. Food Microbiol. 41:85–101 [Google Scholar]
  45. Jones DA, Le D, Smith H, Kojouharov HV. 2002. Bacterial wall attachment in a flow reactor. SIAM J. Appl. Math. 62:1728–71 [Google Scholar]
  46. Jones DA, Smith H. 2000. Microbial competition for nutrient and wall sites in plug flow. SIAM J. Appl. Math. 60:1576–600 [Google Scholar]
  47. Kamada N, Seo S-U, Chen GY, Núñez G. 2013. Role of the gut microbiota in immunity and inflammatory disease. Nat. Rev. Immunol. 13:321–35 [Google Scholar]
  48. Kim HJ, Huh D, Hamilton G, Ingber DE. 2012. Human gut-on-a-chip inhabited by microbial flora that experiences intestinal peristalsis-like motions and flow. Lab. Chip 12:1265–74 [Google Scholar]
  49. Kim HJ, Ingber DE. 2013. Gut-on-a-chip microenvironment induces human intestinal cells to undergo villus differentiation. Integr. Biol. 5:1130–40 [Google Scholar]
  50. Klinger A, Orzekowsky-Schroeder R, von Smolinski D, Blessenohl M, Schueth A. 2012. Complex morphology and functional dynamics of vital murine intestinal mucosa revealed by autofluorescence 2-photon microscopy. Histochem. Cell Biol. 137:269–78 [Google Scholar]
  51. Kontula P, Jaskari J, Nollet L, De Smet I, von Wright A. 1998. The colonization of a simulator of the human intestinal microbial ecosystem by a probiotic strain fed on a fermented oat bran product: effects on the gastrointestinal microbiota. Appl. Microbiol. Biotechnol. 50:246–52 [Google Scholar]
  52. Kovatcheva-Datchary P, Egert M, Maathuis A, Rajilić-Stojanović M, de Graaf AA. et al. 2009. Linking phylogenetic identities of bacteria to starch fermentation in an in vitro model of the large intestine by RNA-based stable isotope probing. Environ. Microbiol. 11:914–26 [Google Scholar]
  53. Laird BD, Van de Wiele TR, Corriveau MC, Jamieson HE, Parsons MB. et al. 2007. Gastrointestinal microbes increase arsenic bioaccessibility of ingested mine tailings using the simulator of the human intestinal microbial ecosystem. Environ. Sci. Technol. 41:5542–47 [Google Scholar]
  54. Lawson DJ, Holtrop G, Flint H. 2011. Bayesian analysis of non-linear differential equation models with application to a gut microbial ecosystem. Biom. J. 53:543–56 [Google Scholar]
  55. Lesmes U, Beards EJ, Gibson GR, Tuohy KM, Shimoni E. 2008. Effects of resistant starch type III polymorphs on human colon microbiota and short chain fatty acids in human gut models. J. Agric. Food Chem. 56:5415–21 [Google Scholar]
  56. Likotrafiti E, Tuohy KM, Gibson GR, Rastall RA. 2014. An in vitro study of the effect of probiotics, prebiotics and synbiotics on the elderly faecal microbiota. Anaerobe 27:50–55 [Google Scholar]
  57. Maathuis AJH, Keller D, Farmer S. 2010. Survival and metabolic activity of the GanedenBC30 strain of Bacillus coagulans in a dynamic in vitro model of the stomach and small intestine. Benef. Microbes 1:31–36 [Google Scholar]
  58. Maathuis AJH, van den Heuvel EG, Schoterman MHC, Venema K. 2012. Galacto-oligosaccharides have prebiotic activity in a dynamic in vitro colon model using a 13C-labelling technique. J. Nutr. 142:1205–12 [Google Scholar]
  59. Maccaferri S, Vitali B, Klinder A, Kolida S, Ndagijimana M. et al. 2010. Rifaximin modulates the colonic microbiota of patients with Crohn's disease: an in vitro approach using a continuous culture colonic model system. J. Antimicrob. Chemother. 65:2556–65 [Google Scholar]
  60. Macfarlane GT, Gibson GR, Cummings JH. 1992. Comparison of fermentation reactions in different regions of the human colon. J. Appl. Bacteriol. 72:57–64 [Google Scholar]
  61. Macfarlane GT, Macfarlane S, Gibson GR. 1998. Validation of a three-stage compound continuous culture system for investigating the effect of retention time on the ecology and metabolism of bacteria in the human colon. Microb. Ecol. 35:180–87 [Google Scholar]
  62. Macfarlane GT, Macfarlane S. 2007. Models for intestinal fermentation: association between food components, delivery systems, bioavailability and functional interactions in the gut. Curr. Opin. Biotech. 18:156–62 [Google Scholar]
  63. Macfarlane S, Woodmansey EJ, Macfarlane GT. 2005. Colonization of mucin by human intestinal bacteria and establishment of biofilm communities in a two-stage continuous culture system. Appl. Environ. Microbiol. 71:7483–92 [Google Scholar]
  64. Maia OB, Duarte R, Silva AM, Cara DC, Nicoli JR. 2001. Evaluation of the components of a commercial probiotic in gnotobiotic mice experimentally challenged with Salmonella enterica subsp. enterica ser. Typhimurium. Vet. Microbiol. 79:183–89 [Google Scholar]
  65. Mäkeläinen H, Mäkivuokko H, Salminen S, Rautonen N, Ouwehand AC. 2007. The effects of polydextrose and xylitol on microbial community and activity in a 4-stage colon simulator. J. Food Sci. 72:153–59 [Google Scholar]
  66. Mäkeläinen H, Forssten S, Saarinen M, Stowell J, Rautonen N, Ouwehand AC. 2009. Xylo-oligosaccharides enhance the growth of bifidobacteria and B. lactis in a simulated colon model. Benef. Microbes 1:81–91 [Google Scholar]
  67. Mäkivuokko H, Saarinen M, Ouwehand A, Rautonen N. 2006. Effects of lactose on colon microbial community structure and function in a four-stage continuous culture system. Biosci. Biotechnol. Biochem. 70:2056–63 [Google Scholar]
  68. Mäkivuokko H, Nurmi J, Nurminen P, Stowell J, Rautonen N. 2005. In vitro effects on polydextrose by colonic bacteria and caco-2 cell cyclooxygenase gene expression. Nutr. Cancer 52:94–104 [Google Scholar]
  69. Malinen E, Mättö J, Salmitie M, Alander M, Saarela M, Palva A. 2002. PCR-ELISA II: analysis of bifidobacterium populations in human faecal samples from a consumption trial with Bifidobacterium lactis Bb-12 and a galacto-oligosaccharide preparation. Syst. Appl. Microbiol. 25:249–58 [Google Scholar]
  70. Marteau P, Minekus M, Havenaar R, Huis In't Veld JHJ. 1997. Survival of lactic acid bacteria in a dynamic model of the stomach and small intestine: validation and the effects of bile. J. Dairy Sci. 80:1031–37 [Google Scholar]
  71. Marteau P, Pochart P, Doré J, Béra-Maillet C, Vernalier A, Corthier G. 2001. Comparative study of bacterial groups within the human cecal and fecal microbiota. Appl. Environ. Microbiol. 67:4929–42 [Google Scholar]
  72. Martinez RCR, Aynaou A-E, Albrecht S, Schols HA, De Martinis ECP. 2011. In vitro evaluation of gastrointestinal survival of Lactobacillus amylovorus DSM 16698 alone and combined with galactooligoaccharides, milk and/or Bifidobacterium animalis subsp. lactis Bb-12. Int. J. Food Microbiol. 149:152–58 [Google Scholar]
  73. Marzorati M, Possemiers S, Van Den Abbeele P, Van De Wiele B, Vanhoecke B, Verstraete W. 2010. Technology and method to study microbial growth and adhesion to host-related surface and the host-microbiota interactions. WO Patent 2010/118857 A2, Ghent Univ. Belgium [Google Scholar]
  74. Marzorati M, Vanhoecke B, Ryck TD, Sadabad MS, Pinheiro I. 2014. The HIM™ module: a new tool to study the host-microbiota interaction in the human gastrointestinal tract in vitro. BMC Microbiol. 14:133 [Google Scholar]
  75. Mestas J, Hughes CCW. 2004. Of mice and not men: differences between mouse and human immunology. J. Immunol. 172:2731–38 [Google Scholar]
  76. Miller TL, Wolin MJ. 1981. Fermentation by the human large intestine microbial community in an in vitro semicontinuous culture system. Appl. Environ. Microbiol. 42:400–7 [Google Scholar]
  77. Minekus M, Marteau P, Havenaar R, Huis In't Veld JHJ. 1995. A multicompartmental dynamic computer-controlled model simulating the stomach and small intestine. Altern. Lab Anim. 23:197–209 [Google Scholar]
  78. Minekus M, Smeets-Peeters M, Bernalier A, Marol-Bonnin S, Havenaar R. et al. 1999. A computer-controlled system to simulate conditions of the large intestine with peristaltic mixing, water absorption and absorption of fermentation products. Appl. Microbiol. Biotechnol. 53:108–14 [Google Scholar]
  79. Molly K, Woestyne MV, Verstraete W. 1993. Development of 5-step multichamber reactor as a simulation of the human intestinal microbial ecosystem. Appl. Microbiol. Biotechnol. 39:254–58 [Google Scholar]
  80. Muñoz-Tamayo R, Laroche B, Walter É, Doré J, Leclerc M. 2010. Mathematical modelling of carbohydrate degradation by human colonic microbiota. J. Theor. Biol. 266:189–201 [Google Scholar]
  81. Muñoz-Tamayo R, Laroche B, Walter É, Doré J, Duncan SH. et al. 2011. Kinetic modelling of lactate utilization and butyrate production by key human colonic bacterial species. FEMS Microbiol. Ecol. 76:615–24 [Google Scholar]
  82. Mysore JV, Duhamel GE. 1994. Morphometric analysis of enteric lesions in C3H/HeN mice inoculated with Serpulina hyodysentericae serotypes 2 and 4 with or without oral streptomycin pretreatment. Can. J. Vet. Res. 58:281–86 [Google Scholar]
  83. Naylor TA, Connolly PC, Martini LG, Elder DP, Minekus M. et al. 2006. Use of a gastrointestinal model and GastroPLUS™ for the prediction of in vivo performance. Ind. Pharm. 12:9–12 [Google Scholar]
  84. Nielsen EM, Schlundt J. 1992. Use of norfloxacin to study colonization ability of Escherichia coli in in vivo and in vitro models of the porcine gut. Antimicrob. Agents Chemother. 36:401–7 [Google Scholar]
  85. Nilsson U, Nyman M. 2007. Carboxylic acids in the hindgut of rats fed highly soluble inulin and Bifidobacterium lactis (Bb-12), Lactobacillus salivarius (UCC500) or Lactobacillus rhamnosus (GG). Scan. J. Food Nutr. 51:13–21 [Google Scholar]
  86. Oufir LE, Barry JL, Flourié B, Cherbut C, Cloarec D. et al. 2000. Relationships between transit time in man and in vitro fermentation of dietary fiber by fecal bacteria. Eur. J. Clin. Nutr. 54:603–9 [Google Scholar]
  87. Ouwehand AC, Kirijavainen PV, Grönlund M-M, Isolauri E, Salminen SJ. 1999. Adhesion of probiotic micro-organisms to intestinal mucus. Int. Dairy J. 9:623–30 [Google Scholar]
  88. Ouwehand AC, Suomalainen T, Tölkko S, Salminen S. 2002. In vitro adhesion of propionic acid bacteria to human intestinal mucus. Le Lait 82:123–30 [Google Scholar]
  89. Payne AN, Zihler A, Chassard C, Lacroix C. 2012. Advances and perspectives in in vitro human gut fermentation modelling. Trends Biotechnol. 30:17–25 [Google Scholar]
  90. Pazzaglia G, Winoto I, Jennings G. 1994. Oral challenge with Aeromonas in protein-malnourished mice. J. Diarrhoeal Dis. Res. 12:108–12 [Google Scholar]
  91. Petrof EO, Gloor GB, Vanner SJ, Weese SJ, Carter D. et al. 2013. Stool substitute transplant therapy for the eradication of Clostridium difficile infection: “RePOOPulating” the gut. Microbiome 1:3 [Google Scholar]
  92. Phillips ML. 2009. Gut reaction: environmental effects on the human microbiota. Environ. Health Perspect. 117:198–205 [Google Scholar]
  93. Pinto M, Robine-Leon S, Appay MD, Kendinger M, Triadou N. et al. 1983. Enterocyte-like differentiation and polarization of the human colon carcinoma cell line Caco-2 in culture. Biol. Cell 47:323–30 [Google Scholar]
  94. Pirt SH. 1974. The theory of fed batch culture with reference to the penicillin fermentation. J. Appl. Chem. Biotechnol. 24:415–24 [Google Scholar]
  95. Pompei A, Cordisco L, Raimondi S, Amaretti A, Pagnoni UM. et al. 2008. In vitro comparison of the prebiotic effects of two inulin-type fructans. Anaerobe 14:280–86 [Google Scholar]
  96. Possemiers S, Bolca S, Grootaert C, Heyerick A, Decroos K. 2006. The prenylflavonoid isoxanthohumol from hops (Humulus lupulus L.) is activated into the potent phytoestrogen 8-prenylnaringenin in vitro and in the human intestine. J. Nutr. 136:1862–67 [Google Scholar]
  97. Probert HM, Gibson GR. 2004. Development of a fermentation system to model sessile bacterial populations in the human colon. Biofilms 1:13–19 [Google Scholar]
  98. Qin J, Ruigiang L, Raes J, Arumugam M, Solvsten B. et al. 2010. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464:59–65 [Google Scholar]
  99. Quigley EM. 2010. Prebiotics and probiotics; modifying and mining the microbiota. Pharmacol. Res. 61:213–18 [Google Scholar]
  100. Quigley ME, Englyst HN. 1992. Determination of neutral sugars and hexosamines by high-performance liquid chromatography with pulsed amperometric detection. Analyst 117:1715–18 [Google Scholar]
  101. Raibaud P, Ducluzeau R, Dubos F, Hudault S, Bewa H, Muller MC. 1980. Implantation of bacteria from the digestive tract of man and various animals into gnotobiotic mice. Am. J. Clin. Nutr. 33:2440–47 [Google Scholar]
  102. Rajilić-Stojanović M, Heilig HGHJ, Molenaar D, Kajander K, Surakka A. et al. 2009. Development and application of the human intestinal tract chip, a phylogenetic microarray: analysis of universally conserved phylotypes in the abundant microbiota of young and elderly adults. Environ. Microbiol. 11:1736–51 [Google Scholar]
  103. Rajilić-Stojanović M, Maathuis A, Heilig HGHJ, Venema K, de Vos WM, Smidt H. 2010. Evaluating the microbial diversity of an in vitro model of the human large intestine by phylogenetic microarray analysis. Microbiology 156:3270–81 [Google Scholar]
  104. Reis PM, Raab TW, Chuat JY, Leser ME, Miller R. et al. 2008. Influence of surfactants on lipase fat digestion in a model gastro-intestinal system. Food Biophys. 3:370–81 [Google Scholar]
  105. Rinttilä T, Kassinen A, Malinen E, Krogius L, Palva A. 2004. Development of an extensive set of 16S rDNA-targeted primers for quantification of pathogenic and indigenous bacteria in faecal samples by real-time PCR. J. Appl. Microbiol. 97:1166–77 [Google Scholar]
  106. Rufener WH Jr, Nelson WO, Wolin MJ. 1963. Maintenance of the rumen microbial population. Appl. Microbiol. 11:196–201 [Google Scholar]
  107. Rumney CJ, Rowland IR. 1992. In vivo and in vitro models of the human colonic flora. Crit. Rev. Food Sci. Nutr. 31:299–331 [Google Scholar]
  108. Salminen S, Bouley C, Boutron-Ruault MC, Cummings JH, Franck A. et al. 1998. Functional food science and gastrointestinal physiology and function. Br. J. Nutr. 80:S147–71 [Google Scholar]
  109. Sannasiddappa TH, Costabile A, Gibson GR, Clarke SR. 2011. The influence of Staphylococcus aureus on gut microbial ecology in an in vitro continuous culture human colonic model system. PLoS ONE 6:e23227 [Google Scholar]
  110. Satokari RM, Vaughan EE, Akkermans ADL, Saarela M, de Vos W. 2001. Bifidobacterial diversity in human feces detected by genus-specific PCR and denaturing gradient gel electrophoresis. Appl. Environ. Microbiol. 67:504–13 [Google Scholar]
  111. Saulnier DMA, Gibson GR, Kolida S. 2008. In vitro effects of selected synbiotics on the human faecal microbiota composition. FEMS Microbiol. Ecol. 66:516–27 [Google Scholar]
  112. Sekirov I, Russell SL, Antunes CM, Finlay BB. 2010. Gut microbiota in health and disease. Physiol. Rev. 90:859–904 [Google Scholar]
  113. Slyter LL, Nelson WO, Wolin MJ. 1964. Modifications of a device for maintenance of the rumen microbial population in continuous culture. Appl. Microbiol. 12:374–77 [Google Scholar]
  114. Stemmons ED, Smith H. 2000. Competition in a chemostat with wall attachment. SIAM J. Appl. Math. 61:567–95 [Google Scholar]
  115. Temmerman R, Swings J. 2004. Identification of lactic acid bacteria: culture-dependent and culture-independent methods. Trends Food Sci. Tech. 15:348–59 [Google Scholar]
  116. Tlaskalová-Hogenová H, Štěpánková R, Kozákova H, Hudcovic T, Vannucci L. et al. 2011. The role of gut microbiota (commensal bacteria) and the mucosal barrier in the pathogenesis of inflammatory and autoimmune diseases and cancer: contribution of germ-free and gnotobiotic animal models of human diseases. Cell. Mol. Immun. 8:100–20 [Google Scholar]
  117. Tremoleda JL, Kerton A, Gsell W. 2012. Anaesthesia and physiology monitoring during in vivo imaging of laboratory rodents: considerations on experimental outcomes and animal welfare. EJNMMI Res. 2:44 [Google Scholar]
  118. Tsilingiri K, Barbosa T, Penna G, Caprioli F, Sonzogni A. et al. 2012. Probiotic and postbiotic activity in health and disease: comparison on a novel polarised ex-vivo organ culture model. Gut 61:1007–15 [Google Scholar]
  119. Turnbaugh PJ, Ridaura VK, Faith JJ, Rey FE, Knight R, Gordon JI. 2009. The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice. Sci. Transl. Med. 1:6ra14 [Google Scholar]
  120. Van de Wiele T, Boeckaert C, Verstraete W, Siciliano S. 2003. Oral exposure PAH: bioactivation processes in the human gut. Commun. Agric. Appl. Biol. Sci. 68:3–6 [Google Scholar]
  121. Van de Wiele T, Boon N, Possemiers S, Jacobs H, Verstraete W. 2004. Prebiotic effects of chicory inulin in the simulator of the human intestinal microbial ecosystem. FEMS Microbio. Ecol. 51:143–53 [Google Scholar]
  122. Van de Wiele T, Boon N, Possemiers S, Jacobs H, Verstraete W. 2007. Inulin-type fructans of longer degree of polymerization exert more pronounced in vitro prebiotic effects. J. Appl. Microbiol. 102:452–60 [Google Scholar]
  123. Van den Abbeele P, Grootaert C, Possemiers S, Verstraete W, Verbeken K, Van de Wiele T. 2009. In vitro model to study the modulation of the mucin-adhered bacterial community. Appl. Microbiol. Biotechnol. 83:349–59 [Google Scholar]
  124. Van den Abbeele P, Grootaert C, Marzorati M, Possemiers S, Verstraete W. et al. 2010. Microbial community development in a dynamic gut model is reproducible, colon region specific, and selective for Bacteroidetes and Clostridium Cluster IX. Appl. Environ. Microbiol. 76:5237–46 [Google Scholar]
  125. Van den Abbeele P, Gérard P, Rabot S, Bruneau A, El Aidy S. et al. 2011. Arabinoxylans and inulin differentially modulate the mucosal and luminal gut microbiota and mucin-degradation in humanized rats. Environ. Microbiol. 13:2667–80 [Google Scholar]
  126. Van den Abbeele P, Roos S, Eeckhaut V, MacKenzie DA, Derde M. et al. 2012. Incorporating a mucosal environment in a dynamic gut model results in a more representative colonization by lactobacilli. Microb. Biotechnol. 5:106–15 [Google Scholar]
  127. Van den Abbeele P, Venema K, Van de Wiele T, Verstraete W, Possemiers S. 2013. Different human gut models reveal the distinct fermentation patterns of arabinoxylan versus inulin. J. Agric. Food Chem. 61:9819–27 [Google Scholar]
  128. Van der Waaij D, Van der Waaij BD. 1990. The colonization resistance of the digestive tract in different animal species and in man; a comparative study. Epidemiol. Infect. 105:237–43 [Google Scholar]
  129. Venema K, Maathuis AJH, Steijart MN, de Graaf AA. 2012. Use of 13C-labelled carbohydrates to trace microbial metabolism in the colon; light in the tunnel!. FASEB J. 26:638.1 [Google Scholar]
  130. Vermeiren J, Possemiers S, Marzorati M, Van de Wiele T. 2011. The gut microbiota as target for innovative drug development: perspectives and a case study of inflammatory bowel disease. Drug Development—A Case Study Based Insight into Modern Strategies C Rundfeldt 1–33 Ghent, Belg.: InTech [Google Scholar]
  131. Wang X, Gibson GR. 1993. Effects of the in vitro fermentation of oligofructose and inulin by bacteria growing in the human large intestine. J. Appl. Bacteriol. 75:373–80 [Google Scholar]
  132. Weigert R, Porat-Shliom N, Amomphimoltham P. 2013. Imaging cell biology in live animals: ready for prime time. J. Cell Biol. 201:969–79 [Google Scholar]
  133. Wieser A, Guggenberfer C, Pritsch M, Heesemann J, Schubert S. 2011. A novel ex vivo set-up for dynamic long-term characterization of processes on mucosal interfaces by confocal imaging and simultaneous cytokine measurements. Cell Microbiol. 13:742–51 [Google Scholar]
  134. Wilkinson MHF. 2002a. Model intestinal microflora in computer simulation (MIMICS). MIMICS Tech. Rep. MIMICS Cellular Automation Program Design and Performance Testing, University of Groningen, The Netherlands. http://www.cs.rug.nl/∼michael/techrep1.pdf [Google Scholar]
  135. Wilkinson MHF. 2002b. Model intestinal microflora in computer simulation (MIMICS). MIMICS Tech. Rep. Ordinary Differential Equations for Modelling Bacterial Interactions in the Gut, University of Groningen, The Netherlands. http://www.cs.rug.nl/∼michael/techrep2.pdf [Google Scholar]
  136. Wilkinson MHF. 2002c. Model intestinal microflora in computer simulation: a simulation and modeling package for host-microflora interactions. IEEE Trans. Biomed. Eng. 49:1077–85 [Google Scholar]
  137. Xu J, Gordon JI. 2003. Inaugural article: honor thy symbionts. Proc. Natl. Acad. Sci. USA 100:10452–59 [Google Scholar]
  138. Zoetendal EG, Akkermans ADL, de Vos WM. 1998. Communities of active bacteria samples reveals stable and host-specific analysis of 16S rRNA from Human fecal temperature gradient gel electrophoresis. Appl. Environ. Microbiol. 64:3854–59 [Google Scholar]

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