The Impact of a Germ Free Perinatal Period on the Variation in Animal Models of Human Inflammatory Diseases – A Review

  • Louise F S Lauritsen Department of Veterinary Disease Biology, Faculty of Life Sciences, University of Copenhagen
  • Majbritt Ravn Hufeldt 1Department of Veterinary Disease Biology, Faculty of Life Sciences, University of Copenhagen and Scanbur Ltd. and Department of Food Science, Faculty of Life Sciences, University of Copenhagen
  • Ben Aasted Department of Veterinary Disease Biology, Faculty of Life Sciences, University of Copenhagen
  • Camilla Hartmann Friis Hansen Department of Veterinary Disease Biology, Faculty of Life Sciences, University of Copenhagen
  • Tore Midtvedt Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet
  • Karsten Buschard Bartholin Institute, Rigshospitalet
  • Axel Kornerup Hansen Department of Veterinary Disease Biology, Faculty of Life Sciences, University of Copenhagen

Abstract

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. 

Section
Articles