Applications of germfree animals Surgical application

To avoid the risk of postoperative wound infection, surgical procedures are carried out in germ-free animals in germ-free isolators. Especially in the field of intestinal surgery, germ-free animals are frequently used to study aspects of wound healing.

Oncology

Some spontaneous murine hematopoietic neoplasms are affected by the absence of a conventional microbial environment, whereas nonhematopoietic tumors are not. Conflicting data were obtained following the introduction of chemical carcinogens in germ-free and conventional mice. The effects of the natural microflora are unclear. Germ-free animals provide an important tool of research in the fight against cancer.

Dental research

The use of germ-free animals and the principles of gnotobiology have provided much information concerning the origin of caries and periodontal disease. The flora in these animal models can be modified, giving information about the cause of both diseases. Also, treatment and prevention can be studied with the help of gnotobiotic animal models.

Microbiology

Studies with germ-free animals are carried out on a large scale to investigate the complex microecologi-cal relationships between microbes themselves and between the microbes and their hosts. One of the most important functions of the intestinal microflora for the host is the phenomenon of colonization resistance, being the force withstanding oral infections. Only the presence of many hundreds of different bio-types of microorganisms in an intestinal tract provides a 'normal' colonization resistance.

Toxicology

In an intestinal tract of a 'normal' animal, the bacterial cells outnumber the cells of the whole body. This means that an enormous metabolic capacity is present in the intestinal tract. Detoxification of a broad variety of toxic products occurs by the normal microflora. With the help of gnotobiotic animals this phenomenon can be investigated in relation to the quality of the microflora.

Nutrition

From the outset of using germ-free animals, nutrition was of utmost importance, due to the sterilization of food necessary to rear germ-free animals. The microchemical environment in the intestine is determined by three factors: chemicals in the diet, chemicals of host origin and chemicals derived by the intestinal microbial flora. By means of gnotobiotic technology, it is possible to change the factors due to diet and microflora to assess the potential impact for the microchemical environment in the intestine.

Immunology

Germ-free animals have provided us with a unique model for studying a true primary response. A reaction to an antigen to which the animal has not previously been exposed is generally considered to be a primary response. During a normal lifespan, however, animals encounter a large number of antigens in the environment that might cross-react with antigens used in investigative work. Germ-free animals can be used as a model to study the question of whether in vitro immune responses were true primary or early secondary responses.

See also: Immune response. Further reading

Coates ME and Gustafsson BE (eds) (1984) The Germ-free Animal in Biomedical Research. Laboratory Animal Handbooks 9. London: Laboratory Animals Ltd. Coates ME, Gordon HA and Wöstmann BS (eds) (1968) The Germ-free Animal in Research. London: Academic Press.

Desplaces A, Zagury D and Sacquet E (1963) Etude de la fonction thyrodienne du rat privé de bactéries. Comptes Rendus Hebdomadaires des Séances de l'Academie des Sciences 257: 756-758. Eaton KA, Suerbaum S, Josenhans C and Krakowka S (1996) Colonization of gnotobiotic piglets by Helicobacter pylori deficient in two flagellin genes. Infection and Immunity 64: 2445-2448. Gordon HA (1959) Morphological and physiological characterization of germfree life. New York Academy of Sciences 78: 208-220. Gordon HA, Wöstmann BS and Bruckner-Kardoss F. (1963) Effects of microbial flora on cardiac output and other elements of blood circulation. Proceedings of the Society for Experimental Biology and Medicine 114: 301-304.

Heneghan JB (ed) (1973) Germfree Research: Biological Effect of Gnotobiotic Environments. London: Academic Press.

Herias MV, Midtvedt T, Hanson LA and Wold At (1995) Role of Escherichia coli P fimbriae in intestinal colonization in gnotobiotic rats. Infection and Immunity 63: 4781^789.

Mirand EA and Back N (eds) (1969) Germ-free Biology: Experimental and Clinical Aspects. New York: Plenum Press.

Miyakawa M and I.uckey TD (eds) (1968) Advances in Germfree Research and Gnotobiology. Proceedings of the International Symposium on Life Germfree Research, Nagoya and lnuyama, Japan, 1967. London: Iliffe Books/Cleveland OH: Chemical Rubber Co. Miyakawa M and Wöstmann BS (eds) (1969) Technology in Germfree and Gnotobiotic Life Research. Tokyo: Academic Press of Japan. Nencki M (1886) Bermerkungen zu einer Bemerkung Pas-

teurs. Archiv für experimentelle Pathologie und Pharm-acokologie 20: 385-388.

Nuttal GHF and Thierfelder H (1895) Tierisches Leben ohne Bakterien im Verdauungskanal I. Zeitschrift für physiologische Chemie 21: 109-121.

Pasteur L (1885) Observations relatives à la note précédente de M. Duclaux. Comptes Rendus de l'Academie des Sciences 100: 68.

Reyniers JA, Trexler PC and Ervin RF (1946) Rearing Germfree Albino Rats. Lobund Report 1: 1-84. Notre Dame IN: University Press.

Schottelius M (1899) Die Bedeutung der Darmbakterien für die Ernährung. I. Archiv für Hygiene 34: 210-243.

Trexler PC and Reynolds LI (1957) Flexible film apparatus for the rearing and use of germfree animals, journal of Applied Microbiology 5: 406-412.

Yuan L, Ward LA, Rosen BI, To TL and Saif LJ 11996) Systematic and intestinal antibody-secreting ccll responses and correlates of protective immunity to human rotavirus in a gnotobiotic pig model of disease. Journal of Virology 70: 3075-3083.

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