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Use of Germ-Free Animal Models in Microbiota-Related Research
1Department of Health Sciences, College of Arts and Sciences, Qatar University, P.O. Box 2713, Doha, Qatar, 2Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden, 3College of Medicine and Health Sciences, Sultan Qaboos University, 123 Alkoudh, Oman
Received: January 14, 2015; Accepted: June 2, 2015
J. Microbiol. Biotechnol. 2015; 25(10): 1583-1588
Published October 28, 2015 https://doi.org/10.4014/jmb.1501.01039
Copyright © The Korean Society for Microbiology and Biotechnology.
Abstract
The large intestine is a home for trillions of microbiota, which confer many benefits on the
host, including production of vitamins, absorption of nutrients, pathogen displacement, and
development of the immune system. For several decades, germ-free animals have been used to
study the interaction between the host and its microbiota. This minireview describes the
technical aspects for establishing and maintaining germ-free animals and highlights the
advantages and disadvantages for germ-free animals as experimental models.
Keywords
Germ-free animals, Germ-free mice, microbiota, Isolator technology
References
- Al-Asmakh M, Anuar F, Zadjali F, Rafter J, Pettersson S. 2012. Gut microbial communities modulating brain development and function. Gut Microbes 3: 366-373.
- Al-Asmakh M, Stukenborg JB, Reda A, Anuar F, Strand ML, Hedin L, et al. 2014. The gut microbiota and developmental programming of the testis in mice. PLoS One 9: e103809.
- Arvidsson C, Hallén A, Bäckhed F. 2012. Generating and analyzing germ-free mice. Curr. Protoc. Mouse Biol. 2: 307-316.
- Bjorkholm B, Bok CM, Lundin A, Rafter J, Hibberd ML, Pettersson S. 2009. Intestinal microbiota regulate xenobiotic metabolism in the liver. PLoS One 4: e6958.
- Braniste V, Al-Asmakh M, Kowal C, Anuar F, Abbaspour A, Toth M, et al. 2014. The gut microbiota influences bloodbrain barrier permeability in mice. Sci. Transl. Med. 6:263ra158.
- Brown K, DeCoffe D, Molcan E, Gibson DL. 2012. Dietinduced dysbiosis of the intestinal microbiota and the effects on immunity and disease. Nutrients 4: 1095-1119.
- Diaz Heijtz R, Wang S, Anuar F, Qian Y, Bjorkholm B, Samuelsson A, et al. 2011. Normal gut microbiota modulates brain development and behavior. Proc. Natl. Acad. Sci. USA 108: 3047-3052.
- Fritz JV, Desai MS, Shah P, Schneider JG, Wilmes P. 2013. From meta-omics to causality: experimental models for human microbiome research. Microbiome 1: 14.
- Goodman AL, Kallstrom G, Faith JJ, Reyes A, Moore A, Dantas G, Gordon JI. 2011. Extensive personal human gut microbiota culture collections characterized and manipulated in gnotobiotic mice. Proc. Natl. Acad. Sci. USA 108: 6252-6257.
- Gootenberg DB, Turnbaugh PJ. 2011. Companion animals symposium: humanized animal models of the microbiome. J. Anim. Sci. 89: 1531-1537.
- Gordon HA, Pesti L. 1971. The gnotobiotic animal as a tool in the study of host microbial relationships. Bacteriol. Rev. 35: 390-429.
- Gustafsson BE. 1959. Lightweight stainless steel systems for rearing germfree animals. Ann. NY Acad. Sci. 78: 17-28.
- Hecht G, Bar-Nathan C, Milite G, Alon I, Moshe Y, Greenfeld L, et al. 2014. A simple cage-autonomous method for the maintenance of the barrier status of germ-free mice during experimentation. Lab. Anim. 48: 292-297.
- Inzunza J, Midtvedt T, Fartoo M, Norin E, Osterlund E, Persson AK, Ahrlund-Richter L. 2005. Germfree status of mice obtained by embryo transfer in an isolator environment. Lab. Anim. 39: 421-427.
- Kostic AD, Howitt MR, Garrett WS. 2013. Exploring hostmicrobiota interactions in animal models and humans. Genes Dev. 27: 701-718.
- McVey Neufeld KA, Perez-Burgos A, Mao YK, Bienenstock J, Kunze WA. 2015. The gut microbiome restores intrinsic and extrinsic nerve function in germ-free mice accompanied by changes in calbindin. Neurogastroenterol. Motil. 27: 627-636.
- Neufeld KM, Kang N, Bienenstock J, Foster JA. 2011. Reduced anxiety-like behavior and central neurochemical change in germ-free mice. Neurogastroenterol. Motil. 23: 255264, e119.
- Nicholson JK, Holmes E, Kinross J, Burcelin R, Gibson G, Jia W, Pettersson S. 2012. Host-gut microbiota metabolic interactions. Science 336: 1262-1267.
- Nicklas W, Baneux P, Boot R, Decelle T, Deeny AA, Fumanelli M, et al. 2002. Recommendations for the health monitoring of rodent and rabbit colonies in breeding and experimental units. Lab. Anim. 36: 20-42.
- O'Hara AM, Shanahan F. 2006. The gut flora as a forgotten organ. EMBO Rep. 7: 688-693.
- Rautava S, Luoto R, Salminen S, Isolauri E. 2012. Microbial contact during pregnancy, intestinal colonization and human disease. Nat. Rev. Gastroenterol. Hepatol. 9: 565-576.
- Sanz Y. 2011. Gut microbiota and probiotics in maternal and infant health. Am. J. Clin. Nutr. 94: 2000S-2005S.
- Shimizu K, Muranaka Y, Fujimura R, Ishida H, Tazume S, Shimamura T. 1998. Normalization of reproductive function in germfree mice following bacterial contamination. Exp. Anim. 47: 151-158.
- Sjogren K, Engdahl C, Henning P, Lerner UH, Tremaroli V, Lagerquist MK, et al. 2012. The gut microbiota regulates bone mass in mice. J. Bone Miner. Res. 27: 1357-1367.
- Smith K, McCoy KD, Macpherson AJ. 2007. Use of axenic animals in studying the adaptation of mammals to their commensal intestinal microbiota. Semin. Immunol. 19: 59-69.
- Sommer F, Backhed F. 2013. The gut microbiota--masters of host development and physiology. Nat. Rev. Microbiol. 11:227-238.
- Stepankova R, Tonar Z, Bartova J, Nedorost L, Rossman P, Poledne R, et al. 2010. Absence of microbiota (germ-free conditions) accelerates the atherosclerosis in ApoE-deficient mice fed standard low cholesterol diet. J. Atheroscler. Thromb. 17: 796-804.
- Wostmann BS. 1981. The germfree animal in nutritional studies. Annu. Rev. Nutr. 1: 257-279.
- Wostmann BS. 1996. Germfree and Gnotobiotic Animal Models:Background and Applications, CRC Press FL, USA.
- Yi P, Li L. 2012. The germfree murine animal: an important animal model for research on the relationship between gut microbiota and the host. Vet. Microbiol. 157: 1-7.
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J. Microbiol. Biotechnol. 2015; 25(10): 1583-1588
Published online October 28, 2015 https://doi.org/10.4014/jmb.1501.01039
Copyright © The Korean Society for Microbiology and Biotechnology.
Use of Germ-Free Animal Models in Microbiota-Related Research
Maha Al-Asmakh 1, 2* and Fahad Zadjali 3
1Department of Health Sciences, College of Arts and Sciences, Qatar University, P.O. Box 2713, Doha, Qatar, 2Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden, 3College of Medicine and Health Sciences, Sultan Qaboos University, 123 Alkoudh, Oman
Received: January 14, 2015; Accepted: June 2, 2015
Abstract
The large intestine is a home for trillions of microbiota, which confer many benefits on the
host, including production of vitamins, absorption of nutrients, pathogen displacement, and
development of the immune system. For several decades, germ-free animals have been used to
study the interaction between the host and its microbiota. This minireview describes the
technical aspects for establishing and maintaining germ-free animals and highlights the
advantages and disadvantages for germ-free animals as experimental models.
Keywords: Germ-free animals, Germ-free mice, microbiota, Isolator technology
References
- Al-Asmakh M, Anuar F, Zadjali F, Rafter J, Pettersson S. 2012. Gut microbial communities modulating brain development and function. Gut Microbes 3: 366-373.
- Al-Asmakh M, Stukenborg JB, Reda A, Anuar F, Strand ML, Hedin L, et al. 2014. The gut microbiota and developmental programming of the testis in mice. PLoS One 9: e103809.
- Arvidsson C, Hallén A, Bäckhed F. 2012. Generating and analyzing germ-free mice. Curr. Protoc. Mouse Biol. 2: 307-316.
- Bjorkholm B, Bok CM, Lundin A, Rafter J, Hibberd ML, Pettersson S. 2009. Intestinal microbiota regulate xenobiotic metabolism in the liver. PLoS One 4: e6958.
- Braniste V, Al-Asmakh M, Kowal C, Anuar F, Abbaspour A, Toth M, et al. 2014. The gut microbiota influences bloodbrain barrier permeability in mice. Sci. Transl. Med. 6:263ra158.
- Brown K, DeCoffe D, Molcan E, Gibson DL. 2012. Dietinduced dysbiosis of the intestinal microbiota and the effects on immunity and disease. Nutrients 4: 1095-1119.
- Diaz Heijtz R, Wang S, Anuar F, Qian Y, Bjorkholm B, Samuelsson A, et al. 2011. Normal gut microbiota modulates brain development and behavior. Proc. Natl. Acad. Sci. USA 108: 3047-3052.
- Fritz JV, Desai MS, Shah P, Schneider JG, Wilmes P. 2013. From meta-omics to causality: experimental models for human microbiome research. Microbiome 1: 14.
- Goodman AL, Kallstrom G, Faith JJ, Reyes A, Moore A, Dantas G, Gordon JI. 2011. Extensive personal human gut microbiota culture collections characterized and manipulated in gnotobiotic mice. Proc. Natl. Acad. Sci. USA 108: 6252-6257.
- Gootenberg DB, Turnbaugh PJ. 2011. Companion animals symposium: humanized animal models of the microbiome. J. Anim. Sci. 89: 1531-1537.
- Gordon HA, Pesti L. 1971. The gnotobiotic animal as a tool in the study of host microbial relationships. Bacteriol. Rev. 35: 390-429.
- Gustafsson BE. 1959. Lightweight stainless steel systems for rearing germfree animals. Ann. NY Acad. Sci. 78: 17-28.
- Hecht G, Bar-Nathan C, Milite G, Alon I, Moshe Y, Greenfeld L, et al. 2014. A simple cage-autonomous method for the maintenance of the barrier status of germ-free mice during experimentation. Lab. Anim. 48: 292-297.
- Inzunza J, Midtvedt T, Fartoo M, Norin E, Osterlund E, Persson AK, Ahrlund-Richter L. 2005. Germfree status of mice obtained by embryo transfer in an isolator environment. Lab. Anim. 39: 421-427.
- Kostic AD, Howitt MR, Garrett WS. 2013. Exploring hostmicrobiota interactions in animal models and humans. Genes Dev. 27: 701-718.
- McVey Neufeld KA, Perez-Burgos A, Mao YK, Bienenstock J, Kunze WA. 2015. The gut microbiome restores intrinsic and extrinsic nerve function in germ-free mice accompanied by changes in calbindin. Neurogastroenterol. Motil. 27: 627-636.
- Neufeld KM, Kang N, Bienenstock J, Foster JA. 2011. Reduced anxiety-like behavior and central neurochemical change in germ-free mice. Neurogastroenterol. Motil. 23: 255264, e119.
- Nicholson JK, Holmes E, Kinross J, Burcelin R, Gibson G, Jia W, Pettersson S. 2012. Host-gut microbiota metabolic interactions. Science 336: 1262-1267.
- Nicklas W, Baneux P, Boot R, Decelle T, Deeny AA, Fumanelli M, et al. 2002. Recommendations for the health monitoring of rodent and rabbit colonies in breeding and experimental units. Lab. Anim. 36: 20-42.
- O'Hara AM, Shanahan F. 2006. The gut flora as a forgotten organ. EMBO Rep. 7: 688-693.
- Rautava S, Luoto R, Salminen S, Isolauri E. 2012. Microbial contact during pregnancy, intestinal colonization and human disease. Nat. Rev. Gastroenterol. Hepatol. 9: 565-576.
- Sanz Y. 2011. Gut microbiota and probiotics in maternal and infant health. Am. J. Clin. Nutr. 94: 2000S-2005S.
- Shimizu K, Muranaka Y, Fujimura R, Ishida H, Tazume S, Shimamura T. 1998. Normalization of reproductive function in germfree mice following bacterial contamination. Exp. Anim. 47: 151-158.
- Sjogren K, Engdahl C, Henning P, Lerner UH, Tremaroli V, Lagerquist MK, et al. 2012. The gut microbiota regulates bone mass in mice. J. Bone Miner. Res. 27: 1357-1367.
- Smith K, McCoy KD, Macpherson AJ. 2007. Use of axenic animals in studying the adaptation of mammals to their commensal intestinal microbiota. Semin. Immunol. 19: 59-69.
- Sommer F, Backhed F. 2013. The gut microbiota--masters of host development and physiology. Nat. Rev. Microbiol. 11:227-238.
- Stepankova R, Tonar Z, Bartova J, Nedorost L, Rossman P, Poledne R, et al. 2010. Absence of microbiota (germ-free conditions) accelerates the atherosclerosis in ApoE-deficient mice fed standard low cholesterol diet. J. Atheroscler. Thromb. 17: 796-804.
- Wostmann BS. 1981. The germfree animal in nutritional studies. Annu. Rev. Nutr. 1: 257-279.
- Wostmann BS. 1996. Germfree and Gnotobiotic Animal Models:Background and Applications, CRC Press FL, USA.
- Yi P, Li L. 2012. The germfree murine animal: an important animal model for research on the relationship between gut microbiota and the host. Vet. Microbiol. 157: 1-7.
