germ free life


Summary: Animals not contaminated by or associated with any foreign organisms.

Top Publications

  1. Backhed F, Ding H, Wang T, Hooper L, Koh G, Nagy A, et al. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A. 2004;101:15718-23 pubmed
    ..Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. AY 667702--AY 668946). ..
  2. Rhee S, Walker W, Cherayil B. Developmentally regulated intestinal expression of IFN-gamma and its target genes and the age-specific response to enteric Salmonella infection. J Immunol. 2005;175:1127-36 pubmed
    ..typhimurium infection resembled that of the wild-type pups. Our findings thus reveal a novel role for IFN-gamma in the developmental regulation of antimicrobial responses in the intestine. ..
  3. Goodman A, McNulty N, Zhao Y, Leip D, Mitra R, Lozupone C, et al. Identifying genetic determinants needed to establish a human gut symbiont in its habitat. Cell Host Microbe. 2009;6:279-89 pubmed publisher
    ..INSeq provides a broadly applicable platform to explore microbial adaptation to the gut and other ecosystems. ..
  4. Tanaka K, Ishikawa H. Role of intestinal bacterial flora in oral tolerance induction. Histol Histopathol. 2004;19:907-14 pubmed publisher
    ..Thus, these bacterias seemed to be important in oral tolerance induction. In addition, the probiotics using these bacteria may be a useful material for the treatment of allergic disorders. ..
  5. Mysorekar I, Lorenz R, Gordon J. A gnotobiotic transgenic mouse model for studying interactions between small intestinal enterocytes and intraepithelial lymphocytes. J Biol Chem. 2002;277:37811-9 pubmed
    ..Together, these findings demonstrate that changes in the proliferative status of the intestinal epithelium affects maturation of gammadelta TCR(+) IELs and produces an influx of alphabeta TCR(+) IELs even in the absence of a microflora. ..
  6. Rawls J, Mahowald M, Ley R, Gordon J. Reciprocal gut microbiota transplants from zebrafish and mice to germ-free recipients reveal host habitat selection. Cell. 2006;127:423-33 pubmed
  7. Gunzer F, Hennig Pauka I, Waldmann K, Mengel M. Gnotobiotic piglets as an animal model for oral infection with O157 and non-O157 serotypes of STEC. Methods Mol Med. 2003;73:307-27 pubmed
  8. Probert C, Williams A, Stepankova R, Tlaskalova Hogenova H, Phillips A, Bland P. The effect of weaning on the clonality of alpha beta T-cell receptor T cells in the intestine of GF and SPF mice. Dev Comp Immunol. 2007;31:606-17 pubmed
    ..These data show: firstly, that under SPF conditions, the intestine is seeded with a diverse T-cell population that becomes oligoclonal around the time of weaning; secondly, that GF mice were oligoclonal at each time point. ..
  9. Ostman S, Rask C, Wold A, Hultkrantz S, Telemo E. Impaired regulatory T cell function in germ-free mice. Eur J Immunol. 2006;36:2336-46 pubmed
    ..We propose that the presence of a microbial flora favors the development of a fully functional Treg population. ..

More Information


  1. Shirkey T, Siggers R, Goldade B, Marshall J, Drew M, Laarveld B, et al. Effects of commensal bacteria on intestinal morphology and expression of proinflammatory cytokines in the gnotobiotic pig. Exp Biol Med (Maywood). 2006;231:1333-45 pubmed
  2. King J, Insall R. Parasexual genetics of Dictyostelium gene disruptions: identification of a ras pathway using diploids. BMC Genet. 2003;4:12 pubmed
    ..They will particularly facilitate generation of multiple mutants and manipulation of essential genes. ..
  3. Walton K, He J, Kelsall B, Sartor R, Fisher N. Dendritic cells in germ-free and specific pathogen-free mice have similar phenotypes and in vitro antigen presenting function. Immunol Lett. 2006;102:16-24 pubmed
    ..In addition, splenic APC from GF mice are fully competent to stimulate naïve T-cell proliferation in vitro. ..
  4. Williams A, Probert C, Stepankova R, Tlaskalova Hogenova H, Phillips A, Bland P. Effects of microflora on the neonatal development of gut mucosal T cells and myeloid cells in the mouse. Immunology. 2006;119:470-8 pubmed
    ..Their activation status depends on the microbiological status of the dam, and without a commensal flora they remain naive. We propose that these cells regulate antigen responsiveness of the developing mucosal T cell pool. ..
  5. Sonnenburg J, Xu J, Leip D, Chen C, Westover B, Weatherford J, et al. Glycan foraging in vivo by an intestine-adapted bacterial symbiont. Science. 2005;307:1955-9 pubmed
    ..This flexible foraging behavior should contribute to ecosystem stability and functional diversity. ..
  6. Rawls J, Mahowald M, Goodman A, Trent C, Gordon J. In vivo imaging and genetic analysis link bacterial motility and symbiosis in the zebrafish gut. Proc Natl Acad Sci U S A. 2007;104:7622-7 pubmed
  7. Chowdhury S, King D, Willing B, Band M, Beever J, Lane A, et al. Transcriptome profiling of the small intestinal epithelium in germfree versus conventional piglets. BMC Genomics. 2007;8:215 pubmed
  8. O Hara A, Shanahan F. The gut flora as a forgotten organ. EMBO Rep. 2006;7:688-93 pubmed
    ..An improved understanding of this hidden organ will reveal secrets that are relevant to human health and to several infectious, inflammatory and neoplastic disease processes. ..
  9. He W, Wang M, Jiang H, Steppan C, Shin M, Thurnheer M, et al. Bacterial colonization leads to the colonic secretion of RELMbeta/FIZZ2, a novel goblet cell-specific protein. Gastroenterology. 2003;125:1388-97 pubmed
    ..These studies define a new goblet cell-specific protein and provide the first evidence that colon-specific gene expression can be regulated by colonization with normal enteric bacteria. ..
  10. Macpherson A, Uhr T. Induction of protective IgA by intestinal dendritic cells carrying commensal bacteria. Science. 2004;303:1662-5 pubmed
  11. Souza D, Vieira A, Soares A, Pinho V, Nicoli J, Vieira L, et al. The essential role of the intestinal microbiota in facilitating acute inflammatory responses. J Immunol. 2004;173:4137-46 pubmed
    ..Thus, the lack of intestinal microbiota is accompanied by a state of active IL-10-mediated inflammatory hyporesponsiveness. ..
  12. Sarma Rupavtarm R, Ge Z, Schauer D, Fox J, Polz M. Spatial distribution and stability of the eight microbial species of the altered schaedler flora in the mouse gastrointestinal tract. Appl Environ Microbiol. 2004;70:2791-800 pubmed
  13. Ryu J, Kim S, Lee H, Bai J, Nam Y, Bae J, et al. Innate immune homeostasis by the homeobox gene caudal and commensal-gut mutualism in Drosophila. Science. 2008;319:777-82 pubmed publisher
    ..These results reveal that a specific genetic deficiency within a host can profoundly influence the gut commensal microbial community and host physiology...
  14. Mutch D, Simmering R, Donnicola D, Fotopoulos G, Holzwarth J, Williamson G, et al. Impact of commensal microbiota on murine gastrointestinal tract gene ontologies. Physiol Genomics. 2004;19:22-31 pubmed
  15. Keilbaugh S, Shin M, Banchereau R, McVay L, Boyko N, Artis D, et al. Activation of RegIIIbeta/gamma and interferon gamma expression in the intestinal tract of SCID mice: an innate response to bacterial colonisation of the gut. Gut. 2005;54:623-9 pubmed
    ..These innate immune responses may play a role in the pathogenesis of colitis in SCID adoptive transfer models in mice and possibly in patients with IBD. ..
  16. Prioult G, Fliss I, Pecquet S. Effect of probiotic bacteria on induction and maintenance of oral tolerance to beta-lactoglobulin in gnotobiotic mice. Clin Diagn Lab Immunol. 2003;10:787-92 pubmed
    ..This study provides evidence that probiotics modulate the oral tolerance response to BLG in mice. The mono-colonization effect is strain-dependant, the best result having been obtained with L. paracasei. ..
  17. Xu J, Gordon J. Honor thy symbionts. Proc Natl Acad Sci U S A. 2003;100:10452-9 pubmed
  18. Fukushima K, Ogawa H, Takahashi K, Naito H, Funayama Y, Kitayama T, et al. Non-pathogenic bacteria modulate colonic epithelial gene expression in germ-free mice. Scand J Gastroenterol. 2003;38:626-34 pubmed
    ..The present study provides a basis for the functional study of each molecule in symbiosis with luminal bacteria in healthy and diseased colon. ..
  19. Karrasch T, Kim J, Muhlbauer M, Magness S, Jobin C. Gnotobiotic IL-10-/-;NF-kappa B(EGFP) mice reveal the critical role of TLR/NF-kappa B signaling in commensal bacteria-induced colitis. J Immunol. 2007;178:6522-32 pubmed
    ..Blocking TLR-induced NF-kappaB activity may represent an attractive strategy to treat immune-mediated intestinal inflammation. ..
  20. Fonty G, Joblin K, Chavarot M, Roux R, Naylor G, Michallon F. Establishment and development of ruminal hydrogenotrophs in methanogen-free lambs. Appl Environ Microbiol. 2007;73:6391-403 pubmed
    ..These findings provide the first evidence from animal studies that reductive acetogens can sustain a functional rumen and replace methanogens as a sink for H(2) in the rumen. ..
  21. Gaboriau Routhiau V, Rakotobe S, Lécuyer E, Mulder I, Lan A, Bridonneau C, et al. The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. Immunity. 2009;31:677-89 pubmed publisher
    ..This bacterium, already known as a potent inducer of mucosal IgA, likely plays a unique role in the postnatal maturation of gut immune functions. Changes in the infant flora may thus influence the development of host immune responses. ..
  22. Cash H, Whitham C, Behrendt C, Hooper L. Symbiotic bacteria direct expression of an intestinal bactericidal lectin. Science. 2006;313:1126-30 pubmed
    ..We propose that these proteins represent an evolutionarily primitive form of lectin-mediated innate immunity, and that they reveal intestinal strategies for maintaining symbiotic host-microbial relationships. ..
  23. Meerts P, Van Gucht S, Cox E, Vandebosch A, Nauwynck H. Correlation between type of adaptive immune response against porcine circovirus type 2 and level of virus replication. Viral Immunol. 2005;18:333-41 pubmed
    ..Absence of PCV2-neutralizing antibodies may be an important factor in the development of an increased virus replication. ..
  24. Strauch U, Obermeier F, Grunwald N, Gürster S, Dunger N, Schultz M, et al. Influence of intestinal bacteria on induction of regulatory T cells: lessons from a transfer model of colitis. Gut. 2005;54:1546-52 pubmed
    ..The results indicate that bacterial antigens are crucial for the generation and/or expansion of T(reg) cells in a healthy individual. Therefore, bacterial colonisation is of great importance in maintaining the immunological balance. ..
  25. Knudsen S, Saadbye P, Hansen L, Collier A, Jacobsen B, Schlundt J, et al. Development and testing of improved suicide functions for biological containment of bacteria. Appl Environ Microbiol. 1995;61:985-91 pubmed
    ..We show that unprecedented suicide efficiency can be achieved in soil and seawater after suicide induction by IPTG (isopropyl-beta-D-thiogalactopyranoside). More than 7 orders of magnitude reduction in suicide bacteria was achieved. ..
  26. Mehrazar K, Gilman Sachs A, Knisley K, Rodkey L, Kim Y. Comparison of the immune response to Ars-BGG in germfree or conventional piglets. Dev Comp Immunol. 1993;17:459-64 pubmed
  27. Annacker O, Burlen Defranoux O, Pimenta Araujo R, Cumano A, Bandeira A. Regulatory CD4 T cells control the size of the peripheral activated/memory CD4 T cell compartment. J Immunol. 2000;164:3573-80 pubmed
  28. Dieleman L, Arends A, Tonkonogy S, Goerres M, Craft D, Grenther W, et al. Helicobacter hepaticus does not induce or potentiate colitis in interleukin-10-deficient mice. Infect Immun. 2000;68:5107-13 pubmed
    ..hepaticus. We conclude that H. hepaticus does not induce or potentiate disease in our IL-10(-/-) mice and therefore is not required to induce colitis in genetically susceptible hosts. ..
  29. Hooper L, Wong M, Thelin A, Hansson L, Falk P, Gordon J. Molecular analysis of commensal host-microbial relationships in the intestine. Science. 2001;291:881-4 pubmed
    ..These findings provide perspectives about the essential nature of the interactions between resident microorganisms and their hosts. ..
  30. Giraud A, Matic I, Tenaillon O, Clara A, Radman M, Fons M, et al. Costs and benefits of high mutation rates: adaptive evolution of bacteria in the mouse gut. Science. 2001;291:2606-8 pubmed
    ..The short-term advantages and long-term disadvantages of mutator bacteria could account for their frequency in nature. ..
  31. Butler J, Sun J, Weber P, Ford S, Rehakova Z, Sinkora J, et al. Antibody repertoire development in fetal and neonatal piglets. IV. Switch recombination, primarily in fetal thymus, occurs independent of environmental antigen and is only weakly associated with repertoire diversification. J Immunol. 2001;167:3239-49 pubmed
  32. Miniello V, Colasanto A, Diaferio L, Galizia I, Jablonska J, Lauriero M, et al. Too fast, too soon to call it "probiotic". Minerva Pediatr. 2010;62:105-7 pubmed
  33. Martins F, Silva A, Vieira A, Barbosa F, Arantes R, Teixeira M, et al. Comparative study of Bifidobacterium animalis, Escherichia coli, Lactobacillus casei and Saccharomyces boulardii probiotic properties. Arch Microbiol. 2009;191:623-30 pubmed publisher
    ..animalis and L. casei for antagonistic substance production. The knowledge of the different probiotic properties could be used to choice the better microorganism depending on the therapeutic or prophylactic application...
  34. Krakowka S, Felsburg P. Gnotobiotics and immunopathology: the use of the gnotobiotic environment to study acquired and inherited immunodeficiency diseases. Vet Immunol Immunopathol. 2005;108:165-75 pubmed
    ..While many issues are unresolved, these data suggest that, through the use of the gnotobiotic environment, xenotransplantation (human-to-dog) may yield a stable and immunologically functional human-dog chimera. ..
  35. Farah C, Gotjamanos T, Seymour G, Ashman R. Cytokines in the oral mucosa of mice infected with Candida albicans. Oral Microbiol Immunol. 2002;17:375-8 pubmed
    ..This study confirms the functional activity of T lymphocytes in reconstituted nude mice, and suggests that TNF-alpha may be an important mediator in the recovery from oropharyngeal candidiasis. ..
  36. Velagapudi V, Hezaveh R, Reigstad C, Gopalacharyulu P, Yetukuri L, Islam S, et al. The gut microbiota modulates host energy and lipid metabolism in mice. J Lipid Res. 2010;51:1101-12 pubmed publisher
    ..Our findings show that the gut microbiota affects both host energy and lipid metabolism and highlights its role in the development of metabolic diseases. ..
  37. Ingegnoli F, Blades M, Manzo A, Wahid S, Perretti M, Panayi G, et al. [Role of cell migration in the pathogenesis of rheumatoid arthritis: in vivo studies in SCID mice transplanted with human synovial membrane]. Reumatismo. 2002;54:128-32 pubmed
  38. Yazawa S, Okada M, Ono M, Fujii S, Okuda Y, Shibata I, et al. Experimental dual infection of pigs with an H1N1 swine influenza virus (A/Sw/Hok/2/81) and Mycoplasma hyopneumoniae. Vet Microbiol. 2004;98:221-8 pubmed
    ..These results demonstrate that the lung lesion of pigs inoculated with M. hyopneumoniae and SIV is more severe than that of pigs inoculated only with M. hyopneumoniae...
  39. Mikkelsen H, Garbarsch C, Tranum Jensen J, Thuneberg L. Macrophages in the small intestinal muscularis externa of embryos, newborn and adult germ-free mice. J Mol Histol. 2004;35:377-87 pubmed
    ..Further, these macrophages are truly resident and appear to have differential responses to exogene stimuli. ..
  40. Oliveira M, Tafuri W, Afonso L, Oliveira M, Nicoli J, Vieira E, et al. Germ-free mice produce high levels of interferon-gamma in response to infection with Leishmania major but fail to heal lesions. Parasitology. 2005;131:477-88 pubmed
    ..These observations indicate that the microbiota is not essential for the development of Th1 immune responses, but seems to be important for macrophage activation. ..
  41. Krakowka S, Ellis J. Evaluation of the effects of porcine genogroup 1 torque teno virus in gnotobiotic swine. Am J Vet Res. 2008;69:1623-9 pubmed publisher
    ..To determine whether porcine genogroup 1 torque teno virus (g1-TTV) can infect and cause disease in gnotobiotic swine...
  42. Oh J, Karam S, Gordon J. Intracellular Helicobacter pylori in gastric epithelial progenitors. Proc Natl Acad Sci U S A. 2005;102:5186-91 pubmed
    ..The notion that adult mammalian epithelial progenitors can function as a repository for H. pylori broadens the view of host habitats available to this and perhaps other pathogens. ..
  43. Laukova A, Guba P, Nemcova R, Vasilková Z. Reduction of Salmonella in gnotobiotic Japanese quails caused by the enterocin A-producing EK13 strain of Enterococcus faecium. Vet Res Commun. 2003;27:275-80 pubmed
    ..Significant reductions were also found in the numbers of S. dusseldorf SA31 strain in the caecum but not in the ileum. ..
  44. Vannucci L, Stepankova R, Grobarova V, Kozakova H, Rossmann P, Klimesova K, et al. Colorectal carcinoma: Importance of colonic environment for anti-cancer response and systemic immunity. J Immunotoxicol. 2009;6:217-26 pubmed publisher
  45. Araki S, Goto S. Dietary restriction in aged mice can partially restore impaired metabolism of apolipoprotein A-IV and C-III. Biogerontology. 2004;5:445-50 pubmed
    ..The present findings suggest that DR initiated even relatively late in life may reduce risk of age-related diseases associated with impaired lipid metabolism. ..
  46. Zhang W, Robertson D, Zhang C, Bai W, Zhao M, Francis D. Escherichia coli constructs expressing human or porcine enterotoxins induce identical diarrheal diseases in a piglet infection model. Appl Environ Microbiol. 2008;74:5832-7 pubmed publisher
    ..Piglets developed identical diarrheal diseases when inoculated with constructs expressing human or porcine enterotoxins. ..
  47. Zaph C, Du Y, Saenz S, Nair M, Perrigoue J, Taylor B, et al. Commensal-dependent expression of IL-25 regulates the IL-23-IL-17 axis in the intestine. J Exp Med. 2008;205:2191-8 pubmed publisher
    ..We propose that acquisition of, or alterations in, commensal bacteria influences intestinal immune homeostasis via direct regulation of the IL-25-IL-23-IL-17 axis. ..
  48. Sung Y, Pineda C, MacRae T, Sorgeloos P, Bossier P. Exposure of gnotobiotic Artemia franciscana larvae to abiotic stress promotes heat shock protein 70 synthesis and enhances resistance to pathogenic Vibrio campbellii. Cell Stress Chaperones. 2008;13:59-66 pubmed publisher
    ..Additionally, the findings are important in aquaculture where development of procedures to prevent bacterial infection of feed stock such as Artemia larvae is a priority. ..
  49. Bernbom N, Licht T, Saadbye P, Vogensen F, Nørrung B. Lactobacillus plantarum inhibits growth of Listeria monocytogenes in an in vitro continuous flow gut model, but promotes invasion of L. monocytogenes in the gut of gnotobiotic rats. Int J Food Microbiol. 2006;108:10-4 pubmed
    ..This observation is however not necessarily specifically related to L. plantarum, and should not be interpreted as the expected effect in animals carrying a conventional intestinal microflora. ..
  50. Zhang W, Wen K, Azevedo M, Gonzalez A, Saif L, Li G, et al. Lactic acid bacterial colonization and human rotavirus infection influence distribution and frequencies of monocytes/macrophages and dendritic cells in neonatal gnotobiotic pigs. Vet Immunol Immunopathol. 2008;121:222-31 pubmed
  51. Duarte R, Silva A, Vieira L, Afonso L, Nicoli J. Influence of normal microbiota on some aspects of the immune response during experimental infection with Trypanosoma cruzi in mice. J Med Microbiol. 2004;53:741-8 pubmed
    ..cruzi in mice. However, the increase in production of cytokines that is linked to resistance to this parasite did not alter the outcome of infection significantly, probably due to high virulence of the Y strain. ..
  52. Laszik Z, Blakey G. Searching for a valid animal model of hemolytic uremic syndrome. Am J Clin Pathol. 2002;118:323-5 pubmed
  53. Ribeiro Sobrinho A, de Melo Maltos S, Farias L, de Carvalho M, Nicoli J, de Uzeda M, et al. Cytokine production in response to endodontic infection in germ-free mice. Oral Microbiol Immunol. 2002;17:344-53 pubmed
    ..In vivo, however, a predominance of the immune response to one species over the others occurred...