Skip to main content Accessibility help
×
×
Home

The intestinal microbiota in the rat model: major breakthroughs from new technologies

  • Julie Tomas (a1), Philippe Langella (a1) and Claire Cherbuy (a1)
Abstract

The mammalian intestine harbors a large and diverse community of micro-organisms, known as the intestinal microbiota. Recent developments in molecular profiling methods, mainly based on microbial 16S ribosomal RNA gene sequencing, have provided unprecedented insights into the make-up and diversity of intestinal microbial communities. Using these culture-independent analyses, gut microbiota of several mammals including laboratory rodents, have been revisited. The laboratory rat is one of the major species bred and kept for scientific research. Although this animal is bred in confined environments and subjected to procedures for satisfying health requirements that hamper natural colonization, some major features of mammalian gut microbiota are conserved. However, the gut microbiota varies according to the breeding conditions of the rats and this could impact reproducibility of the experimental models. Determining the non-pathogenic microbial community might be relevant in standards of quality control of laboratory animals. Molecular profiling techniques could be applied to document this information.

Copyright
Corresponding author
*Corresponding author. E-mail: Claire.Cherbuy@jouy.inra.fr
References
Hide All
Abbott, A (2009)s. Return of the rat. Nature 460: 788.
Adlerberth, I and Wold, AE (2009). Establishment of the gut microbiota in Western infants. Acta Paediatrica 98: 229238.
Alpert, C, Sczesny, S, Gruhl, B and Blaut, M (2008). Long-term stability of the human gut microbiota in two different rat strains. Current Issues in Molecular Biology 10: 1724.
Becker, N, Kunath, J, Loh, G and Blaut, M (2011). Human intestinal microbiota: characterization of a simplified and stable gnotobiotic rat model. Gut Microbes 2: 2533.
Berard, M, Megard, C and Montagutelli, X (2004). Are clean rodents good models for man? In The 9th FELASA Symposium, Nantes, France.
Bernbom, N, Norrung, B, Saadbye, P, Molbak, L, Vogensen, FK and Licht, TR (2006). Comparison of methods and animal models commonly used for investigation of fecal microbiota: effects of time, host and gender. Journal of Microbiological Methods 66: 8795.
Bowey, E, Adlercreutz, H and Rowland, I (2003). Metabolism of isoflavones and lignans by the gut microflora: a study in germ-free and human flora associated rats. Food and Chemical Toxicology 41: 631636.
Brooks, SP, McAllister, M, Sandoz, M and Kalmokoff, ML (2003). Culture-independent phylogenetic analysis of the faecal flora of the rat. Canadian Journal of Microbiology 49: 589601.
Buhnik-Rosenblau, K, Danin-Poleg, Y and Kashi, Y (2011). Predominant effect of host genetics on levels of Lactobacillus johnsonii bacteria in the mouse gut. Applied and Environmental Microbiology 77: 65316538.
Carter, P and Foster, H (2006). Gnotobiotics. In: Suckow, M, Weisbroth, S and Franklin, C (eds) The Laboratory Rat, 2nd edn. Elsevier Academic Press, Burlington, pp. 693710.
Cherbuy, C, Andrieux, C, Honvo-Houeto, E, Thomas, M, Ide, C, Druesne, N, Chaumontet, C, Darcy-Vrillon, B and Duee, PH (2004). Expression of mitochondrial HMGCoA synthase and glutaminase in the colonic mucosa is modulated by bacterial species. European Journal of Biochemistry 271: 8795.
Cherbuy, C, Honvo-Houeto, E, Bruneau, A, Bridonneau, C, Mayeur, C, Duee, PH, Langella, P and Thomas, M (2010). Microbiota matures colonic epithelium through a coordinated induction of cell cycle-related proteins in gnotobiotic rat. American Journal of Physiological Gastrointestinal and Liver Physiology 299: G348G357.
Dalby, AB, Frank, DN, St Amand, AL, Bendele, AM and Pace, NR (2006). Culture-independent analysis of indomethacin-induced alterations in the rat gastrointestinal microbiota. Applied and Environmental Microbiology 72: 67076715.
Davey, KJ, O'Mahony, SM, Schellekens, H, O'Sullivan, O, Bienenstock, J, Cotter, PD, Dinan, TG and Cryan, JF (2012). Gender-dependent consequences of chronic olanzapine in the rat: effects on body weight, inflammatory, metabolic and microbiota parameters. Psychopharmacology (Berlin) 221: 155169.
de La Serre, CB, Ellis, CL, Lee, J, Hartman, AL, Rutledge, JC and Raybould, HE (2010). Propensity to high-fat diet-induced obesity in rats is associated with changes in the gut microbiota and gut inflammation. American Journal of Physiological Gastrointestinal and Liver Physiology 299: G440G448.
de Waard, R, Snel, J, Bokken, GC, Tan, PS, Schut, F and Huis In't Veld, JH (2002). Comparison of faecal Lactobacillus populations in experimental animals from different breeding facilities and possible consequences for probiotic studies. Letters in Applied Microbiology 34: 105109.
Delroisse, JM, Boulvin, AL, Parmentier, I, Dauphin, RD, Vandenbol, M and Portetelle, D (2008). Quantification of Bifidobacterium spp. and Lactobacillus spp. in rat fecal samples by real-time PCR. Research in Microbiology 163: 663670.
Dethlefsen, L, McFall-Ngai, M and Relman, DA (2007). An ecological and evolutionary perspective on human-microbe mutualism and disease. Nature 449: 811818.
Dewhirst, FE, Chien, CC, Paster, BJ, Ericson, RL, Orcutt, RP, Schauer, DB and Fox, JG (1999). Phylogeny of the defined murine microbiota: altered Schaedler flora. Applied and Environmental Microbiology 65: 32873292.
Dinoto, A, Suksomcheep, A, Ishizuka, S, Kimura, H, Hanada, S, Kamagata, Y, Asano, K, Tomita, F and Yokota, A (2006). Modulation of rat cecal microbiota by administration of raffinose and encapsulated Bifidobacterium breve. Applied and Environmental Microbiology 72: 784792.
Dostal, A, Chassard, C, Hilty, FM, Zimmermann, MB, Jaeggi, T, Rossi, S and Lacroix, C (2012). Iron depletion and repletion with ferrous sulfate or electrolytic iron modifies the composition and metabolic activity of the gut microbiota in rats. Journal of Nutrition 142: 271277.
Dumas, ME, Wilder, SP, Bihoreau, MT, Barton, RH, Fearnside, JF, Argoud, K, D'Amato, L, Wallis, RH, Blancher, C, Keun, HC, Baunsgaard, D, Scott, J, Sidelmann, UG, Nicholson, JK and Gauguier, D (2007). Direct quantitative trait locus mapping of mammalian metabolic phenotypes in diabetic and normoglycemic rat models. Nature Genetics 39: 666672.
Edwards, CA, Rumney, C, Davies, M, Parrett, AM, Dore, J, Martin, F, Schmitt, J, Stahl, B, Norin, E, Midtvedt, T, Rowland, IR, Heavey, P, Köhler, H, Stocks, B and Schroten, H (2003). A human flora-associated rat model of the breast-fed infant gut. Journal of Pediatric Gastroenterology and Nutrition 37: 168177.
Fak, F, Ahrne, S, Molin, G, Jeppsson, B and Westrom, B (2008). Microbial manipulation of the rat dam changes bacterial colonization and alters properties of the gut in her offspring. American Journal of Physiological Gastrointestinal and Liver Physiology 294: G148–154.
Frese, SA, Benson, AK, Tannock, GW, Loach, DM, Kim, J, Zhang, M, Oh, PL, Heng, NC, Patil, PB, Juge, N, Mackenzie, DA, Pearson, BM, Lapidus, A, Dalin, E, Tice, H, Goltsman, E, Land, M, Hauser, L, Ivanova, N, Kyrpides, NC and Walter, J (2011). The evolution of host specialization in the vertebrate gut symbiont Lactobacillus reuteri. PLoS Genetics 7: e1001314.
Friswell, MK, Gika, H, Stratford, IJ, Theodoridis, G, Telfer, B, Wilson, ID and McBain, AJ (2010). Site and strain-specific variation in gut microbiota profiles and metabolism in experimental mice. PLoS One 5: e8584.
Fushuku, S and Fukuda, K (2008). Inhomogeneity of fecal flora in separately reared laboratory mice, as detected by denaturing gradient gel electrophoresis (DGGE). Experimental Animals 57: 9599.
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 and Cerf-Bensussan, N (2009). The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. Immunity 31: 677689.
Gerard, P, Beguet, F, Lepercq, P, Rigottier-Gois, L, Rochet, V, Andrieux, C and Juste, C (2004). Gnotobiotic rats harboring human intestinal microbiota as a model for studying cholesterol-to-coprostanol conversion. FEMS Microbiology Ecology 47: 337343.
Gerritsen, J, Smidt, H, Rijkers, GT and de Vos, WM (2011). Intestinal microbiota in human health and disease: the impact of probiotics. Genes and Nutrition 6: 209240.
Geuking, MB, Cahenzli, J, Lawson, MA, Ng, DC, Slack, E, Hapfelmeier, S, McCoy, KD and Macpherson, AJ (2011). Intestinal bacterial colonization induces mutualistic regulatory T cell responses. Immunity 34: 794806.
Gibbs, RA, Weinstock, GM, Metzker, ML, Muzny, DM, Sodergren, EJ, Scherer, S, Scott, G, Steffen, D, Worley, KC, Burch, PE, et al. (2004). Genome sequence of the Brown Norway rat yields insights into mammalian evolution. Nature 428: 493521.
Gill, SR, Pop, M, Deboy, RT, Eckburg, PB, Turnbaugh, PJ, Samuel, BS, Gordon, JI, Relman, DA, Fraser-Liggett, CM and Nelson, KE (2006). Metagenomic analysis of the human distal gut microbiome. Science 312: 13551359.
Glad, T, Bernhardsen, P, Nielsen, KM, Brusetti, L, Andersen, M, Aars, J and Sundset, MA (2010). Bacterial diversity in faeces from polar bear (Ursus maritimus) in Arctic Svalbard. BMC Microbiology 10: 10.
Gootenberg, DB and Turnbaugh, PJ (2011). Companion animals symposium: humanized animal models of the microbiome. Journal of Animal Science 89: 15311537.
Hansen, A, Ejsing-Duun, M, AASTED, B, Josephsen, J, GB Christensen, FV, Hufeldt, M and Buschard, K (2007). The impact of the postnatal gut microbiota on animal models. In The 10th FELASA Symposium and the XIV ICLAS General Assembly and Conference, Cernobbio, Italy.
Hedrich, H (2006). Taxonomy and stocks and strains. In: Suckow, M, Weisbroth, S and Franklin, C (eds) The Laboratory Rat, 2nd edn, Elsevier Academic Press, pp. 7192.
Hufeldt, MR, Nielsen, DS, Vogensen, FK, Midtvedt, T and Hansen, AK (2010). Variation in the gut microbiota of laboratory mice is related to both genetic and environmental factors. Comparative Medicine 60: 336347.
Iannaccone, PM and Jacob, HJ (2009). Rats! Disease Models and Mechanisms 2: 206210.
Inoue, R and Ushida, K (2003a). Development of the intestinal microbiota in rats and its possible interactions with the evolution of the luminal IgA in the intestine. FEMS Microbiology Ecology 45: 147153.
Inoue, R and Ushida, K (2003b). Vertical and horizontal transmission of intestinal commensal bacteria in the rat model. FEMS Microbiology Ecology 46: 213219.
Islam, KB, Fukiya, S, Hagio, M, Fujii, N, Ishizuka, S, Ooka, T, Ogura, Y, Hayashi, T and Yokota, A (2011). Bile acid is a host factor that regulates the composition of the cecal microbiota in rats. Gastroenterology 141: 17731781.
Jacob, HJ (2010). The rat: a model used in biomedical research. Methods in Molecular Biology 597: 111.
Jacob, HJ, Lazar, J, Dwinell, MR, Moreno, C and Geurts, AM (2010). Gene targeting in the rat: advances and opportunities. Trends in Genetics 26: 510518.
Joly, F, Mayeur, C, Bruneau, A, Noordine, ML, Meylheuc, T, Langella, P, Messing, B, Duee, PH, Cherbuy, C and Thomas, M (2010). Drastic changes in fecal and mucosa-associated microbiota in adult patients with short bowel syndrome. Biochimie 92: 753761.
Jussi, V, Erkki, E and Paavo, T (2005). Comparison of cellular fatty acid profiles of the microbiota in different gut regions of BALB/c and C57BL/6J mice. Antonie Van Leeuwenhoek 88: 6774.
Karlsson, CL, Molin, G, Fak, F, Johansson Hagslatt, ML, Jakesevic, M, Hakansson, A, Jeppsson, B, Westrom, B and Ahrne, S (2011). Effects on weight gain and gut microbiota in rats given bacterial supplements and a high-energy-dense diet from fetal life through to 6 months of age. British Journal of Nutrition 106: 887895.
Ketabi, A, Dieleman, LA and Ganzle, MG (2011). Influence of isomalto-oligosaccharides on intestinal microbiota in rats. Journal of Applied Microbiology 110: 12971306.
Lauritsen, LFS, Hufeldt, MR, Aasted, B, Friis Hansen, CH, Midtvedt, T, Buschard, K and Hansen, AK (2010). The impact of a germ free perinatal period on the variation in animal models of human inflammatory diseases – a review. Scandinavian Journal of Laboratory Animal Science 37: 4354.
Leser, TD, Amenuvor, JZ, Jensen, TK, Lindecrona, RH, Boye, M and Moller, K (2002). Culture-independent analysis of gut bacteria: the pig gastrointestinal tract microbiota revisited. Applied and Environmental Microbiology 68: 673690.
Ley, RE, Hamady, M, Lozupone, C, Turnbaugh, PJ, Ramey, RR, Bircher, JS, Schlegel, ML, Tucker, TA, Schrenzel, MD, Knight, R and Gordon, JI (2008). Evolution of mammals and their gut microbes. Science 320: 16471651.
Ley, RE, Peterson, DA and Gordon, JI (2006). Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell 124: 837848.
Li, JV, Reshat, R, Wu, Q, Ashrafian, H, Bueter, M, le Roux, CW, Darzi, A, Athanasiou, T, Marchesi, JR, Nicholson, JK, Holmes, E and Gooderham, NJ (2011). Experimental bariatric surgery in rats generates a cytotoxic chemical environment in the gut contents. Frontiers in Microbiology 2: 183.
Licht, TR, Hansen, M, Bergstrom, A, Poulsen, M, Krath, BN, Markowski, J, Dragsted, LO and Wilcks, A (2010). Effects of apples and specific apple components on the cecal environment of conventional rats: role of apple pectin. BMC Microbiology 10: 13.
Licht, TR, Hansen, M, Poulsen, M and Dragsted, LO (2006). Dietary carbohydrate source influences molecular fingerprints of the rat faecal microbiota. BMC Microbiology 6: 98.
Manichanh, C, Reeder, J, Gibert, P, Varela, E, Llopis, M, Antolin, M, Guigo, R, Knight, R and Guarner, F (2010). Reshaping the gut microbiome with bacterial transplantation and antibiotic intake. Genome Research 20: 14111419.
Mashimo, T and Serikawa, T (2009). Rat resources in biomedical research. Current Pharmaceutical Biotechnology 10: 214220.
Neish, AS (2009). Microbes in gastrointestinal health and disease. Gastroenterology 136: 6580.
Nelson, TA, Holmes, S, Alekseyenko, AV, Shenoy, M, Desantis, T, Wu, CH, Andersen, GL, Winston, J, Sonnenburg, J, Pasricha, PJ and Spormann, A (2011). PhyloChip microarray analysis reveals altered gastrointestinal microbial communities in a rat model of colonic hypersensitivity. Journal of Neurogastroenterology and Motility 23: 169177, e141–162.
Norin, E and Midtvedt, T (2010). Intestinal microflora functions in laboratory mice claimed to harbor a “normal” intestinal microflora. Is the SPF concept running out of date? Anaerobe 16: 311313.
Orcutt, R, Gianni, F and Judge, R (1987). Development of an ‘Altered Schaedler Flora’ for NCI gnotobiotic rodents. Microecology and Therapy 17: 59.
Pontoizeau, C, Fearnside, JF, Navratil, V, Domange, C, Cazier, JB, Fernandez-Santamaria, C, Kaisaki, PJ, Emsley, L, Toulhoat, P, Bihoreau, MT, Nicholson, JK, Gauguier, D and Dumas, ME (2011). Broad-ranging natural metabotype variation drives physiological plasticity in healthy control inbred rat strains. Journal of Proteome Research 10: 16751689.
Qi, H, Xiang, Z, Han, G, Yu, B, Huang, Z and Chen, D (2011). Effects of different dietary protein sources on cecal microflora in rats. African Journal of Biotechnology 10: 37043708.
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, Li, S, Jian, M, Zhou, Y, Li, Y, Zhang, X, Li, S, Qin, N, Yang, H, Wang, J, Brunak, S, Doré, J, Guarner, F, Kristiansen, K, Pedersen, O, Parkhill, J, Weissenbach, J; MetaHIT Consortium, Bork, P, Ehrlich, D and Wang, J (2010). A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464: 5965.
Roesch, LF, Lorca, GL, Casella, G, Giongo, A, Naranjo, A, Pionzio, AM, Li, N, Mai, V, Wasserfall, CH, Schatz, D, Neu, J, Triplett, EW (2009). Culture-independent identification of gut bacteria correlated with the onset of diabetes in a rat model. ISME Journal 3: 536548.
Rohde, CM, Wells, DF, Robosky, LC, Manning, ML, Clifford, CB, Reily, MD and Robertson, DG (2007). Metabonomic evaluation of Schaedler altered microflora rats. Chemical Research in Toxicology 20: 13881392.
Rul, F, Ben-Yahia, L, Chegdani, F, Wrzosek, L, Thomas, S, Noordine, ML, Gitton, C, Cherbuy, C, Langella, P and Thomas, M (2011). Impact of the metabolic activity of Streptococcus thermophilus on the colon epithelium of gnotobiotic rats. Journal of Biological Chemistry 286: 1028810296.
Russel Lindsey, J and Baker, H (2006). Historical foundations. In: Suckow, M, Weisbroth, S and Franklin, C (eds) The Laboratory Rat, 2nd edn, Elsevier Academic Press, pp. 151.
Salzman, NH, de Jong, H, Paterson, Y, Harmsen, HJ, Welling, GW and Bos, NA (2002). Analysis of 16S libraries of mouse gastrointestinal microflora reveals a large new group of mouse intestinal bacteria. Microbiology 148: 36513660.
Schaedler, RW, Dubs, R and Costello, R (1965). Association of germfree mice with bacteria isolated from normal mice. Journal of Experimental Medicine 122: 7782.
Spor, A, Koren, O and Ley, R (2011). Unravelling the effects of the environment and host genotype on the gut microbiome. Nature Reviews Microbiology 9: 279290.
Stehr, M, Greweling, MC, Tischer, S, Singh, M, Blocker, H, Monner, DA and Muller, W (2009). Charles River altered Schaedler flora (CRASF) remained stable for four years in a mouse colony housed in individually ventilated cages. Lab Animal 43: 362370.
Teran-Ventura, E, Roca, M, Martin, MT, Abarca, ML, Martinez, V and Vergara, P (2010). Characterization of housing-related spontaneous variations of gut microbiota and expression of toll-like receptors 2 and 4 in rats. Microbial Ecology 60: 691702.
Thomas, M, Wrzosek, L, Ben-Yahia, L, Noordine, ML, Gitton, C, Chevret, D, Langella, P, Mayeur, C, Cherbuy, C and Rul, F (2011). Carbohydrate metabolism is essential for the colonization of Streptococcus thermophilus in the digestive tract of gnotobiotic rats. PLoS One 6: e28789.
Tlaskalova-Hogenova, H, Stepankova, R, Kozakova, H, Hudcovic, T, Vannucci, L, Tuckova, L, Rossmann, P, Hrncir, T, Kverka, M, Zakostelska, Z, Klimešová, K, Přibylová, J, Bártová, J, Sanchez, D, Fundová, P, Borovská, D, Srůtková, D, Zídek, Z, Schwarzer, M, Drastich, P, Funda, DP (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. Cellular and Molecular Immunology 8: 110120.
Turnbaugh, PJ, Ley, RE, Mahowald, MA, Magrini, V, Mardis, ER and Gordon, JI (2006). An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444: 10271031.
Vaahtovuo, J, Toivanen, P and Eerola, E (2003). Bacterial composition of murine fecal microflora is indigenous and genetically guided. FEMS Microbiology Ecology 44: 131136.
Valladares, R, Sankar, D, Li, N, Williams, E, Lai, KK, Abdelgeliel, AS, Gonzalez, CF, Wasserfall, CH, Larkin, J, Schatz, D, Atkinson, MA, Triplett, EW, Neu, J, Lorca, GL (2010). Lactobacillus johnsonii N6.2 mitigates the development of type 1 diabetes in BB-DP rats. PLoS One 5: e10507.
Whitford, MF, Teather, RM and Forster, RJ (2001). Phylogenetic analysis of methanogens from the bovine rumen. BMC Microbiology 1: 5.
Yanabe, M, Shibuya, M, Gonda, T, Asai, H, Tanaka, T, Sudou, K, Narita, T and Itoh, K (2001). Establishment of specific pathogen-free (SPF) rat colonies using gnotobiotic techniques. Experimental Animals 50: 293298.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Animal Health Research Reviews
  • ISSN: 1466-2523
  • EISSN: 1475-2654
  • URL: /core/journals/animal-health-research-reviews
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed