Comparative analysis of intestinal tract models.

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.

[1]  H. Flint,et al.  Bayesian analysis of non‐linear differential equation models with application to a gut microbial ecosystem , 2011, Biometrical journal. Biometrische Zeitschrift.

[2]  W. Verstraete,et al.  Inulin‐type fructans of longer degree of polymerization exert more pronounced in vitro prebiotic effects , 2007, Journal of applied microbiology.

[3]  W. Verstraete,et al.  The effect of probiotic strains on the microbiota of the Simulator of the Human Intestinal Microbial Ecosystem (SHIME). , 1999, International journal of food microbiology.

[4]  I R Rowland,et al.  In vivo and in vitro models of the human colonic flora. , 1992, Critical reviews in food science and nutrition.

[5]  E. Nielsen,et al.  Use of norfloxacin to study colonization ability of Escherichia coli in in vivo and in vitro models of the porcine gut , 1992, Antimicrobial Agents and Chemotherapy.

[6]  G. Gibson,et al.  Bacterial, SCFA and gas profiles of a range of food ingredients following in vitro fermentation by human colonic microbiota. , 2010, Anaerobe.

[7]  Hal L. Smith,et al.  Microbial Competition for Nutrient and Wall Sites in Plug Flow , 2000, SIAM J. Appl. Math..

[8]  R. Weigert,et al.  Imaging cell biology in live animals: Ready for prime time , 2013, The Journal of cell biology.

[9]  B. Finlay,et al.  Gut microbiota in health and disease. , 2010, Physiological reviews.

[10]  W. D. de Vos,et al.  Intestinal microbiota in human health and disease: the impact of probiotics , 2011, Genes & Nutrition.

[11]  W. Verstraete,et al.  The prenylflavonoid isoxanthohumol from hops (Humulus lupulus L.) is activated into the potent phytoestrogen 8-prenylnaringenin in vitro and in the human intestine. , 2006, The Journal of nutrition.

[12]  S. Salminen,et al.  The effects of polydextrose and xylitol on microbial community and activity in a 4-stage colon simulator. , 2007, Journal of food science.

[13]  G. Gibson,et al.  The Influence of Staphylococcus aureus on Gut Microbial Ecology in an In Vitro Continuous Culture Human Colonic Model System , 2011, PloS one.

[14]  A. Wellmer,et al.  Growth of Candida albicans in normal and altered faecal flora in the model of continuous flow culture , 1995, Mycoses.

[15]  G. Gibson,et al.  Development of a fermentation system to model sessile bacterial populations in the human colon , 2004 .

[16]  M. Nyman,et al.  Carboxylic acids in the hindgut of rats fed highly soluble inulin and Bifidobacterium lactis (Bb-12), Lactobacillus salivarius (UCC500) or Lactobacillus rhamnosus (GG) , 2007, Scandinavian Journal of Food & Nutrition.

[17]  G. Macfarlane,et al.  Colonization of Mucin by Human Intestinal Bacteria and Establishment of Biofilm Communities in a Two-Stage Continuous Culture System , 2005, Applied and Environmental Microbiology.

[18]  W. Verstraete,et al.  Oral exposure to PAH: bioactivation processes in the human gut. , 2003, Communications in agricultural and applied biological sciences.

[19]  S. Pirt,et al.  The theory of fed batch culture with reference to the penicillin fermentation , 1974 .

[20]  Y. Nakamura,et al.  Influence of Bacillus subtilis C-3102 on microbiota in a dynamic in vitro model of the gastrointestinal tract simulating human conditions. , 2012, Beneficial microbes.

[21]  S. Raimondi,et al.  In vitro comparison of the prebiotic effects of two inulin-type fructans. , 2008, Anaerobe.

[22]  W. Verstraete,et al.  Gastrointestinal microbes increase arsenic bioaccessibility of ingested mine tailings using the simulator of the human intestinal microbial ecosystem. , 2007, Environmental science & technology.

[23]  Maria Saarela,et al.  Bifidobacterial Diversity in Human Feces Detected by Genus-Specific PCR and Denaturing Gradient Gel Electrophoresis , 2001, Applied and Environmental Microbiology.

[24]  W. D. de Vos,et al.  Linking phylogenetic identities of bacteria to starch fermentation in an in vitro model of the large intestine by RNA-based stable isotope probing. , 2009, Environmental microbiology.

[25]  W. Verstraete,et al.  Different human gut models reveal the distinct fermentation patterns of Arabinoxylan versus inulin. , 2013, Journal of agricultural and food chemistry.

[26]  S. Hicks,et al.  Adhesion of enteroaggregative Escherichia coli to pediatric intestinal mucosa in vitro , 1996, Infection and immunity.

[27]  T. Mattila-Sandholm,et al.  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 , 1998, Applied Microbiology and Biotechnology.

[28]  S. Hubbell,et al.  Single-nutrient microbial competition: qualitative agreement between experimental and theoretically forecast outcomes. , 1980, Science.

[29]  G. Gibson,et al.  Effects of resistant starch type III polymorphs on human colon microbiota and short chain fatty acids in human gut models. , 2008, Journal of agricultural and food chemistry.

[30]  E. Quigley Prebiotics and probiotics; modifying and mining the microbiota. , 2010, Pharmacological research.

[31]  E. Zoetendal,et al.  Arabinoxylans and inulin differentially modulate the mucosal and luminal gut microbiota and mucin-degradation in humanized rats. , 2011, Environmental microbiology.

[32]  D. Ingber,et al.  Human gut-on-a-chip inhabited by microbial flora that experiences intestinal peristalsis-like motions and flow. , 2012, Lab on a chip.

[33]  K. Venema,et al.  Galacto-oligosaccharides have prebiotic activity in a dynamic in vitro colon model using a (13)C-labeling technique. , 2012, The Journal of nutrition.

[34]  G. Macfarlane,et al.  The control and consequences of bacterial fermentation in the human colon. , 1991, The Journal of applied bacteriology.

[35]  D. C. Cara,et al.  Evaluation of the components of a commercial probiotic in gnotobiotic mice experimentally challenged with Salmonella enterica subsp. enterica ser. Typhimurium. , 2001, Veterinary microbiology.

[36]  E. Zoetendal,et al.  Temperature Gradient Gel Electrophoresis Analysis of 16S rRNA from Human Fecal Samples Reveals Stable and Host-Specific Communities of Active Bacteria , 1998, Applied and Environmental Microbiology.

[37]  S. Gorbach,et al.  Colonization resistance of the human intestinal microflora: Testing the hypothesis in normal volunteers , 1988, European Journal of Clinical Microbiology and Infectious Diseases.

[38]  D. von Smolinski,et al.  Complex morphology and functional dynamics of vital murine intestinal mucosa revealed by autofluorescence 2-photon microscopy , 2012, Histochemistry and Cell Biology.

[39]  M. G. Gabridge Parabiotic Chamber for Organ Cultures: Improved Model , 1974, Applied microbiology.

[40]  J. Heesemann,et al.  A novel ex vivo set‐up for dynamic long‐term characterization of processes on mucosal interfaces by confocal imaging and simultaneous cytokine measurements , 2011, Cellular microbiology.

[41]  G. Macfarlane,et al.  Adherence and Cytokine Induction in Caco-2 Cells by Bacterial Populations from a Three-Stage Continuous-Culture Model of the Large Intestine , 2011, Applied and Environmental Microbiology.

[42]  R. van der Meer,et al.  In Silico Model as a Tool for Interpretation of Intestinal Infection Studies , 2006, Applied and Environmental Microbiology.

[43]  M. Roberfroid,et al.  Functional food science and gastrointestinal physiology and function , 1998, British Journal of Nutrition.

[44]  M. Rescigno,et al.  Probiotic and postbiotic activity in health and disease: comparison on a novel polarised ex-vivo organ culture model , 2012, Gut.

[45]  D. Gibbons,et al.  Mouse and human intestinal immunity: same ballpark, different players; different rules, same score , 2011, Mucosal Immunology.

[46]  S. Salminen,et al.  Adhesion of probiotic micro-organisms to intestinal mucus , 1999 .

[47]  M. Mcmurdo,et al.  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. , 2005, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[48]  A. Majkowska,et al.  Selection of probiotics and prebiotics for synbiotics and confirmation of their in vivo effectiveness , 2002 .

[49]  Philippe Marteau,et al.  A Multicompartmental Dynamic Computer-controlled Model Simulating the Stomach and Small Intestine , 1995 .

[50]  G. Gibson,et al.  An in vitro study of the effect of probiotics, prebiotics and synbiotics on the elderly faecal microbiota. , 2014, Anaerobe.

[51]  Massimo Marzorati,et al.  The Gut Microbiota as Target for Innovative Drug Development: Perspectives and a Case Study of Inflammatory Bowel Diseases , 2011 .

[52]  F. Bornet,et al.  Relationships between transit time in man and in vitro fermentation of dietary fiber by fecal bacteria , 2000, European Journal of Clinical Nutrition.

[53]  J. Doré,et al.  Mathematical modelling of carbohydrate degradation by human colonic microbiota. , 2010, Journal of theoretical biology.

[54]  M. Hazenberg,et al.  Effects of the human intestinal flora on germ-free mice. , 1981, The Journal of applied bacteriology.

[55]  Hristo V. Kojouharov,et al.  Bacterial Wall Attachment in a Flow Reactor , 2002, SIAM J. Appl. Math..

[56]  Hal L. Smith,et al.  Competition in a Chemostat with Wall Attachment , 2000, SIAM J. Appl. Math..

[57]  D. Jones,et al.  Microbial Competition in Reactors with Wall Attachment , 2001, Microbial Ecology.

[58]  M. Ballyk,et al.  A model of microbial growth in a plug flow reactor with wall attachment. , 1999, Mathematical biosciences.

[59]  G. Macfarlane,et al.  Models for intestinal fermentation: association between food components, delivery systems, bioavailability and functional interactions in the gut. , 2007, Current opinion in biotechnology.

[60]  J. Gordon,et al.  Honor thy symbionts , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[61]  Willy Verstraete,et al.  The HMI™ module: a new tool to study the Host-Microbiota Interaction in the human gastrointestinal tract in vitro , 2014, BMC Microbiology.

[62]  P. Brigidi,et al.  Rifaximin modulates the colonic microbiota of patients with Crohn's disease: an in vitro approach using a continuous culture colonic model system. , 2010, The Journal of antimicrobial chemotherapy.

[63]  W. Verstraete,et al.  Prebiotic effects of chicory inulin in the simulator of the human intestinal microbial ecosystem. , 2004, FEMS microbiology ecology.

[64]  G. Macfarlane,et al.  Comparison of fermentation reactions in different regions of the human colon. , 1992, The Journal of applied bacteriology.

[65]  C. Chassard,et al.  Advances and perspectives in in vitro human gut fermentation modeling. , 2012, Trends in biotechnology.

[66]  M. Pinto,et al.  Enterocyte-like differentiation and polarization of the human colon carcinoma cell line Caco-2 in culture , 1983 .

[67]  A. Ouwehand,et al.  Effects of Lactose on Colon Microbial Community Structure and Function in a Four-Stage Semi-Continuous Culture System , 2006, Bioscience, biotechnology, and biochemistry.

[68]  G. Gibson,et al.  Effects of the in vitro fermentation of oligofructose and inulin by bacteria growing in the human large intestine. , 1993, The Journal of applied bacteriology.

[69]  Willy Gsell,et al.  Anaesthesia and physiological monitoring during in vivo imaging of laboratory rodents: considerations on experimental outcomes and animal welfare , 2012, EJNMMI Research.

[70]  T. Miller,et al.  Fermentation by the human large intestine microbial community in an in vitro semicontinuous culture system , 1981, Applied and environmental microbiology.

[71]  W. D. de Vos,et al.  Novel Polyfermentor Intestinal Model (PolyFermS) for Controlled Ecological Studies: Validation and Effect of pH , 2013, PloS one.

[72]  J. Swings,et al.  Identification of lactic acid bacteria: culture-dependent and culture-independent methods , 2004 .

[73]  W. Verstraete,et al.  Comparison of prebiotic effects of arabinoxylan oligosaccharides and inulin in a simulator of the human intestinal microbial ecosystem. , 2009, FEMS microbiology ecology.

[74]  D. Waaij,et al.  The colonization resistance of the digestive tract in different animal species and in man; a comparative study , 1990 .

[75]  Gerwin C. Raangs,et al.  Variations of Bacterial Populations in Human Feces Measured by Fluorescent In Situ Hybridization with Group-Specific 16S rRNA-Targeted Oligonucleotide Probes , 1998, Applied and Environmental Microbiology.

[76]  M. Quigley,et al.  Determination of neutral sugars and hexosamines by high-performance liquid chromatography with pulsed amperometric detection , 1992 .

[77]  W. Verstraete,et al.  In vitro model to study the modulation of the mucin-adhered bacterial community , 2009, Applied Microbiology and Biotechnology.

[78]  G. Jennings,et al.  Oral challenge with Aeromonas in protein-malnourished mice. , 1994, Journal of diarrhoeal diseases research.

[79]  W. Verstraete,et al.  Incorporating a mucosal environment in a dynamic gut model results in a more representative colonization by lactobacilli , 2011, Microbial biotechnology.

[80]  E. Zoetendal,et al.  Microbial Community Development in a Dynamic Gut Model Is Reproducible, Colon Region Specific, and Selective for Bacteroidetes and Clostridium Cluster IX , 2010, Applied and Environmental Microbiology.

[81]  D. Maskell,et al.  Development of an ex vivo organ culture model using human gastro-intestinal tissue and Campylobacter jejuni. , 2006, FEMS microbiology letters.

[82]  Albert A de Graaf,et al.  Gaining insight into microbial physiology in the large intestine: a special role for stable isotopes. , 2008, Advances in microbial physiology.

[83]  R. Wiegert,et al.  A simulation of microbial competition in the human colonic ecosystem , 1996, Applied and environmental microbiology.

[84]  A. Palva,et al.  Development of an extensive set of 16S rDNA‐targeted primers for quantification of pathogenic and indigenous bacteria in faecal samples by real‐time PCR , 2004, Journal of applied microbiology.

[85]  G. Duhamel,et al.  Morphometric analysis of enteric lesions in C3H/HeN mice inoculated with Serpulina hyodysenteriae serotypes 2 and 4 with or without oral streptomycin pretreatment. , 1994, Canadian journal of veterinary research = Revue canadienne de recherche veterinaire.

[86]  M. Pop,et al.  Metagenomic Analysis of the Human Distal Gut Microbiome , 2006, Science.

[87]  G. Macfarlane,et al.  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 , 1988, Applied and environmental microbiology.

[88]  E. Zoetendal,et al.  In vitro evaluation of gastrointestinal survival of Lactobacillus amylovorus DSM 16698 alone and combined with galactooligosaccharides, milk and/or Bifidobacterium animalis subsp. lactis Bb-12. , 2011, International journal of food microbiology.

[89]  W. Verstraete,et al.  Development of a 5-step multi-chamber reactor as a simulation of the human intestinal microbial ecosystem , 1993, Applied Microbiology and Biotechnology.

[90]  Eric Walter,et al.  Kinetic modelling of lactate utilization and butyrate production by key human colonic bacterial species. , 2011, FEMS microbiology ecology.

[91]  A. Ouwehand,et al.  Xylo-oligosaccharides enhance the growth of bifidobacteria and Bifidobacterium lactis in a simulated colon model. , 2010, Beneficial microbes.

[92]  R. Havenaar,et al.  A computer-controlled system to simulate conditions of the large intestine with peristaltic mixing, water absorption and absorption of fermentation products , 1999, Applied Microbiology and Biotechnology.

[93]  A. Maathuis,et al.  Survival and metabolic activity of the GanedenBC30 strain of Bacillus coagulans in a dynamic in vitro model of the stomach and small intestine. , 2010, Beneficial microbes.

[94]  M. Phillips Gut Reaction: Environmental Effects on the Human Microbiota , 2009, Environmental health perspectives.

[95]  P. Raibaud,et al.  Implantation of bacteria from the digestive tract of man and various animals into gnotobiotic mice. , 1980, The American journal of clinical nutrition.

[96]  I. Fliss,et al.  Immobilization of Infant Fecal Microbiota and Utilization in an in vitro Colonic Fermentation Model , 2004, Microbial Ecology.

[97]  G. Macfarlane,et al.  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 , 1998, Microbial Ecology.

[98]  R. Havenaar,et al.  Survival of lactic acid bacteria in a dynamic model of the stomach and small intestine: validation and the effects of bile. , 1997, Journal of dairy science.

[99]  Sofia Kolida,et al.  In vitro effects of selected synbiotics on the human faecal microbiota composition. , 2008, FEMS microbiology ecology.

[100]  J. Stowell,et al.  In Vitro Effects on Polydextrose by Colonic Bacteria and Caco-2 Cell Cyclooxygenase Gene Expression , 2005, Nutrition and cancer.

[101]  S. Salminen,et al.  In vitro adhesion of propionic acid bacteria to human intestinal mucus , 2002 .

[102]  J. Mathers,et al.  Estimation of the fermentability of dietary fibre in vitro: a European interlaboratory study , 1995, British Journal of Nutrition.

[103]  Sang-Uk Seo,et al.  Role of the gut microbiota in immunity and inflammatory disease , 2013, Nature Reviews Immunology.

[104]  W. D. de Vos,et al.  Evaluating the microbial diversity of an in vitro model of the human large intestine by phylogenetic microarray analysis. , 2010, Microbiology.

[105]  R. Knight,et al.  The Effect of Diet on the Human Gut Microbiome: A Metagenomic Analysis in Humanized Gnotobiotic Mice , 2009, Science Translational Medicine.

[106]  W. D. de Vos,et al.  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 , 2009, Environmental microbiology.

[107]  W. Verstraete,et al.  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) , 2000, Applied Microbiology and Biotechnology.

[108]  A. Palva,et al.  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. , 2002, Systematic and applied microbiology.

[109]  J. Nikkilä,et al.  Gut microbiota of healthy elderly NSAID users is selectively modified with the administration of Lactobacillus acidophilus NCFM and lactitol , 2011, AGE.

[110]  Mary Ballyk,et al.  Effects of Random Motility on Microbial Growth and Competition in a Flow Reactor , 1998, SIAM J. Appl. Math..

[111]  P. Bork,et al.  A human gut microbial gene catalogue established by metagenomic sequencing , 2010, Nature.

[112]  T. Raab,et al.  Influence of Surfactants on Lipase Fat Digestion in a Model Gastro-intestinal System , 2008, Food biophysics.

[113]  R. Havenaar,et al.  Use of a gastro-intestinal model and gastroplus[tm] for the prediction of in vivo performance , 2006 .

[114]  R. Tanaka,et al.  Increased resistance of mice to Salmonella enterica serovar Typhimurium infection by synbiotic administration of Bifidobacteria and transgalactosylated oligosaccharides , 2001, Journal of applied microbiology.

[115]  R. Freter,et al.  CHAPTER 2 – Mechanisms That Control the Microflora in the Large Intestine , 1983 .

[116]  G. Gloor,et al.  Stool substitute transplant therapy for the eradication of Clostridium difficile infection: ‘RePOOPulating’ the gut , 2013, Microbiome.

[117]  M. Lasik,et al.  Bioconversion of grape and chokeberry wine polyphenols during simulated gastrointestinal in vitro digestion , 2011, International journal of food sciences and nutrition.

[118]  M. Wolin,et al.  MODIFICATIONS OF A DEVICE FOR MAINTENANCE OF THE RUMEN MICROBIAL POPULATION IN CONTINUOUS CULTURE. , 1964, Applied microbiology.

[119]  C. Hughes,et al.  Of Mice and Not Men: Differences between Mouse and Human Immunology , 2004, The Journal of Immunology.

[120]  B. R. Berends,et al.  Identification and quantification of risk factors in animal management and transport regarding Salmonella spp. in pigs. , 1996, Journal of food microbiology.

[121]  Michael H. F. Wilkinson Model intestinal microflora in computer simulation: a simulation and modeling package for host-microflora interactions , 2002, IEEE Transactions on Biomedical Engineering.

[122]  H. Sugiyama,et al.  Susceptibility to enteric botulinum colonization of antibiotic-treated adult mice , 1982 .

[123]  R. Satokari,et al.  Persistence of Colonization of Human Colonic Mucosa by a Probiotic Strain, Lactobacillus rhamnosusGG, after Oral Consumption , 1999, Applied and Environmental Microbiology.

[124]  B. Flourié,et al.  Effects of Bifidobacterium sp fermented milk ingested with or without inulin on colonic bifidobacteria and enzymatic activities in healthy humans. , 1996, European journal of clinical nutrition.

[125]  M. Wolin,et al.  Maintenance of the rumen microbial population in continuous culture. , 1963, Applied microbiology.

[126]  J. Doré,et al.  Comparative Study of Bacterial Groups within the Human Cecal and Fecal Microbiota , 2001, Applied and Environmental Microbiology.

[127]  J. H. I. Huis in't Veld,et al.  Overview of gut flora and probiotics. , 1998, International journal of food microbiology.

[128]  W. D. de Vos,et al.  Profiling human gut bacterial metabolism and its kinetics using [U‐13C]glucose and NMR , 2010, NMR in biomedicine.

[129]  M. Wilkinson,et al.  Models to Study Colonisation and Colonisation Resistance , 2000 .

[130]  G. Gibson,et al.  Factors Involved in the In Vitro Fermentability of Short Carbohydrates in Static Faecal Batch Cultures , 2012 .

[131]  Donald E Ingber,et al.  Gut-on-a-Chip microenvironment induces human intestinal cells to undergo villus differentiation. , 2013, Integrative biology : quantitative biosciences from nano to macro.

[132]  L. Vannucci,et al.  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 , 2011, Cellular and Molecular Immunology.

[133]  I. Rowland,et al.  In Vitro Fermentation of NUTRIOSE® FB06, a Wheat Dextrin Soluble Fibre, in a Continuous Culture Human Colonic Model System , 2013, PloS one.

[134]  Christophe Lacroix,et al.  New three-stage in vitro model for infant colonic fermentation with immobilized fecal microbiota. , 2006, FEMS microbiology ecology.