Inflammatory diseases in mouse models are under strong impact from the gut microbiota. Therefore increased interindividual gut microbiota similarity may be seen as a way to reduce group sizes in mouse experiments. The composition of the gut microbiota is to a high extent defined by genetics, and it is known that selecting siblings as mothers even in inbred colonies may increase the gut microbiota similarity among the mice with 3-4%. We therefore hypothesized that selective breeding of mice aiming at a high similarity in the gut microbiota would increase the interindividual similarity of the gut microbiota. BALB/cCrl mice were, however, found to have a mean heterozygosity of only 0.8% in their genome, and selection of breeders with a high similarity in the gut microbiota for three generations did not change the overall gut microbiota similarity, which was 66% in the P generation and 66%, 64% and 63% in the F1, F2 and F3 generations, respectively. Increased gut microbiota similarity in closely related mice in inbred mouse colonies is, therefore, more likely to be caused by other factors, such as imprinting or different intrauterine conditions, rather than by residual heterozygosity.