Gastrointestinal structure and function in germ-free or gnotobiotic animals A truly germ-free animal harbours no associated forms of life, including viruses. Occasionally the term 'germ-free' has been used in a more restricted sense to denote animals that are free of pathogens only. For this reason it is preferable to use the term 'axenic' or the more general term 'gnotobiotic', when referring to animals in which the composition of any associated fauna or flora (biota), if present, is fully defined. Gnotobiotic animals, unless deliberately contaminated, are bacteria free but may harbour congenitally transmitted agents such as the leukaemogenic virus, found in most strains of what are usually referred to as 'germ-free' mice. Some of the advantages of investigating animals free of associated microbes were recognized even during the pioneering days of microbiology, as shown by the first report of the rearing of such animals'. Primarily because of technical difficulties, their use was greatly restricted until simple inexpensive apparatus made ofplastic film was developed2. At present the most commonly used species in germ-free work are mice, rats, and chickens. Germ-free rats and mice are available in large numbers from both institutional and commercial colonies, some of which have been maintained continuously since 1954. Recently, methods for obtaining and using germ-free animals have been simplified further by the development of disposable isolation apparatus which can be used for the larger animals, including pigs and even calves3, as illustrated in Figures 1 and 2. These isolators can be used to contain animals that are infected with highly contagious pathogens as well as to exclude all microorganisms. Clinically, on an experimental basis, isolators have been used for surgical procedures and in the treatment of patients with extensive burns or those who have been immunosuppressed4. It seems likely that apparatus which so effectively controls cross-infection in the laboratory can also be used to solve similar problems in the hospital. This brief review does not attempt to cover all the physiological differences between conventional and germ-free animals but focuses on those relating to gastrointestinal morphology and function. A comprehensive treatise on the germ-free animal in research has already been published5. The Germ-free Gastrointestinal Tract MORPHOLOGY OF THE SMALL INTESTINE The small intestine of germ-free animals differs from the conventional in several important respects. The germ-free intestinal wall looks and is thinner, not only because it is less cellular, but also because it is less well hydrated. The villi of germ-free dogs are the same length as those in conventional 230

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