Why use Germfree or Gnotobiotic Animals in Biomedical Research?

The cross-talk between the macro- and microorganisms and microbe-microbe communication in vivo is of great scientific interest under both physiological and patho-physiological conditions in biomedical research. These areas are e.g. of importance when studying effects/functions related to the intestine such as when using antibiotics, in allergy, regarding innate and mucosal immunity and molecular pathogenesis, introduction of 'functional food products' and other dietary components as well as in inflammatory bowel diseases. Much of microbe-microbe communication studies can today be performed in vitro, but the qourum sensing and other ecological evaluations must and can most elegantly be clarified when working within gnotobiology. Gnotobiology means working with a host organism under known conditions, i.e., at our laboratory, we have rats and mice under germfree or gnotobiotic conditions (gnotos is greek and means known; thus germfree animals have received/been inoculated/are housing a known flora). Thus, microbe-microbe and host-microbe communications on both molecular, cellular as well as tissue/organ level can be evaluated.

Today, little is known about how members of the intestinal microflora interact with the host to establish a mutual beneficial relationship. This is the main goal for the research within the field. By using these animals, any anatomical structures, physiological, biochemical or immunological functions in a macroorganism, which has been influenced by the microflora can be studied and the control material in these studies are the
germfree animals or healthy new - borns - ahealthy baby is always born germfree.

Over the years, groups within gnotobiology have been working with both basic and applied medicine, i.e. evaluations of the role of the flora on different surfaces on the body and the cross-talk with its host. Initially, basic knowledge about steroid and bile acid metabolism and the role of the intestinal microbes was evaluated within our group. Later, our group has studied the establishment of the normal intestinal flora under different conditions in different animal species and in humans. Today, we are also evaluating the role of 'functional food products' on the intestinal functions, the effect on the intestinal flora in organisms during treatment with different antimicrobial drugs, the role of the flora during metabolism of many dietary components and also e.g. (pro)carcinogenic substances. Moreover, basic knowledge within the immunological area is of great interest, and basic knowledge obtained using germfree animals is today of a great value in e.g. areas such as the role of intestinal flora establishment in relation to development of allergy during early childhood.

The Laboratory of Medical Microbial Ecology within the Department of Cell & Molecular Biology at the Karolinska Institute, where Elisabeth Norin is the Head, is the only group within this field in Sweden. Today the group also acts as a Core Facility, in order to serve as a resource for the whole country, both within basic science and as platforms within drug and food industries. At the laboratory, there are strains of both germfree rats and mice, inbread for many generations and germfree transgenes available.

The facility has also possibilities to help costumers to get transgenic and/or knock-out animals germfree by embryo transfer into a germfree isolator, and these animals can later be contaminated with microbes of specific scientific interest.

Elisabeth (Lissa) Norin, Associate Professor
Laboratory of Medical Microbial Ecology
von Eulers väg 5
Box 285
Karolinska Institute
171 77 Stockholm
Sweden

e-mail: Elisabeth.Norin@cmb.ki.se