Variation in the Gut Microbiota of Laboratory Mice Is Related to Both Genetic and Environmental Factors

During recent years, the composition of the gut microbiota (GM) has received increasing attention as a factor in the development of experimental inflammatory disease in animal models. Because increased variation in the GM might lead to increased variation in disease parameters, determining and reducing GM variation between laboratory animals may provide more consistent models. Both genetic and environmental aspects influence the composition of the GM and may vary between laboratory animal breeding centers and within an individual breeding center. This study investigated the variation in cecal microbiota in 8-wk-old NMRI and C57BL/6 mice by using denaturing gradient gel electrophoresis to profile PCR-derived amplicons from bacterial 16S rRNA genes. Comparison of the cecal microbiotas revealed that the similarity index of the inbred C57BL/6Sca strain was 10% higher than that of the outbred Sca:NMRI stock. Comparing C57BL/6 mice from 2 vendors revealed significant differences in the microbial profile, whereas the profiles of C57BL/6Sca mice raised in separate rooms within the same breeding center were not significantly different. Furthermore, housing in individually ventilated cages did not lead to intercage variation. These results show that denaturing gradient gel electrophoresis is a simple tool that can be used to characterize the gut microbiota of mice. Including such characterizations in future quality-control programs may increase the reproducibility of mouse studies

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.