The Impact of a Germ Free Perinatal Period on the Variation in Animal Models of Human Inflammatory Diseases – A Review
Bacteria prime the immune system in early life, which in the first place is relevant for the development of oral tolerance. For some disease models, such as those for inflammatory bowel disease, germ free status for an entire life span, leads to the absence of prominent disease symptoms, while for other models, such as the Type 1 diabetes-prone NOD mouse, germ free status in early life would increase the incidence to a maximum. Basically both reactions are dependent on how the immune system has been primed in early life, i.e. with which bacteria and at which age. After early life priming, the gut regulatory immunity seems to be stable and less prone to be influenced by the gut flora. However, disease development later in life will still be dependent on contact with microorganisms to induce the inflammatory response. The aim of this review is to analyze whether it is reasonable to assume that variation in animal models, and thereby reduced groups size in experiments, may be achieved if animals are reared germ free with subsequent inoculation of a standardized gut flora at a standard age.