Reducing the variation in animal models by standardizing the gut microbiota

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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.

Denaturing gradient gel electrophoresis (DGGE) - a culture independent approach separating PCR-derived DNA amplicons of bacterial 16S rRNA - were used to study GM composition. We analyzed the GM in several different studies, including the impact of GM on disease development. Our studies demonstrated that inbred mice (C57BL/6Sca) had a 10% point higher similarity in GM composition compared to outbred mice (Sca:NMRI). C57BL/6 purchased from two breeders revealed significant differences in the microbial profile and by changing the breeding setup for the inbred strain C57BL/6Sca the variation in the GM between the offspring could be reduced. We also found indications that controlled postnatal bacterial exposure at different time points in NMRI mice lead to differences in the microbial gut profile later in life. In leptin deficient B6.Lepob/J mice a significant correlation was found between variation in the GM and variation in glucose intolerance, and antibiotic manipulations of the GM in C57BL/6 mice changed the glucose tolerance without affecting weight or mucosal immunity.

Further investigations concerning the mechanisms of how GM influences disease development is necessary, but based on these results it seems reasonable to assume that by manipulating the GM we may produce animal models of inflammatory and immunological origin with less variation, which will provide the researchers with better results and enable them to use smaller group sizes in the individual study.
Original languageEnglish
Publication dateMay 2011
Publication statusPublished - May 2011

ID: 35317005