Life style associated diseases such as type 1 and 2 diabetes mellitus, atherosclerosis and inflammatory bowel disease originate form an adaptive immune response, which can be down regulated by a regulatory immune response and are under heavy stimulation from early life gut microbiota (GM). Today, a large proportion of laboratory animals are used to study such diseases, but inter-individual variation in these animal models leads to the need for larger group sizes to reach statistical significance and adequate power. By standardizing the microbial and immunological status of laboratory animals we may therefore be able to produce animals with a more standardized response and less variation. This would lead to more precise results and a reduced number of animals needed for statistical significance.

The aim of the present study was to investigate if the composition of the GM of B6.V-Lepob/J leptin deficient mouse, a model of severe obesity and type 2 diabetes, was correlated with development of glucose intolerance. GM composition was analyzed by means of denaturing gradient gel electrophoresis (DGGE), a culture independent approach, separating PCR-derived DNA amplicons of bacterial 16S rRNA. Disease development was monitored by weekly weight and blood glucose measurements supplemented with measurements of oral glucose tolerance, HbA1c%, plasma insulin and plasma cytokines. A significant correlation was demonstrated between GM composition and glucose intolerance. Also, a significant correlation was found between blood glucose, HbA1c% and glucose intolerance and the pro-inflammatory cytokine IL-12, supporting the correlation found between gut and disease, as IL-12 is secreted after microbial stimulation of immunological cells – e.g. In the gut.

Further investigations concerning the mechanisms of how the GM influences disease development is necessary, but based on these results it seems reasonable to assume, that by controlling the GM we may also influence disease development of type 2 diabetes in B6.V-Lepob/J leptin deficient mice, and thereby produce animals with less variation, which will provide the researchers better results and enable them to use smaller group sizes in the individual study.