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Microbiology and Molecular Biology Reviews, December 1998, p. 1157-1170, Vol. 62, No. 4
1092-2172/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Creating and Maintaining the Gastrointestinal Ecosystem: What We Know and Need To Know from Gnotobiology

Per G. Falk,1,dagger Lora V. Hooper,1 Tore Midtvedt,2 and Jeffrey I. Gordon1,*

Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110,1 and Laboratory of Medical Microbial Ecology, Karolinska Institute, S-17177 Stockholm, Sweden2

Studying the cross talk between nonpathogenic organisms and their mammalian hosts represents an experimental challenge because these interactions are typically subtle and the microbial societies that associate with mammalian hosts are very complex and dynamic. A large, functionally stable, climax community of microbes is maintained in the murine and human gastrointestinal tracts. This open ecosystem exhibits not only regional differences in the composition of its microbiota but also regional differences in the differentiation programs of its epithelial cells and in the spatial distribution of its component immune cells. A key experimental strategy for determining whether "nonpathogenic" microorganisms actively create their own regional habitats in this ecosystem is to define cellular function in germ-free animals and then evaluate the effects of adding single or several microbial species. This review focuses on how gnotobiotics---the study of germ-free animals---has been and needs to be used to examine how the gastrointestinal ecosystem is created and maintained. Areas discussed include the generation of simplified ecosystems by using genetically manipulatable microbes and hosts to determine whether components of the microbiota actively regulate epithelial differentiation to create niches for themselves and for other organisms; the ways in which gnotobiology can help reveal collaborative interactions among the microbiota, epithelium, and mucosal immune system; and the ways in which gnotobiology is and will be useful for identifying host and microbial factors that define the continuum between nonpathogenic and pathogenic. A series of tests of microbial contributions to several pathologic states, using germ-free and ex-germ-free mice, are proposed.

* Corresponding author. Mailing address: Department of Molecular Biology and Pharmacology, Box 8103, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110. Phone: (314) 362-7243. Fax: (314) 362-7047. E-mail: jgordon{at}pharmsun.wustl.edu.

dagger Present address: Department of Molecular Biology, ASTRA Hässle AB, S-431 83 Mölndal, Sweden.

Microbiology and Molecular Biology Reviews, December 1998, p. 1157-1170, Vol. 62, No. 4
1092-2172/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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