Host’s fitness can be affected by its genotype and gut microbiota, defined as the microbes living in the host’s intestinal tract. This study explored how the genetic diversity of the host influences its bacterial communities in the context of captive breeding programs, for the critically endangered European mink (Mustela lutreola). As stated by the ecosystem on a leash model, mechanisms such as inbreeding depression may lead to changes in immunomodulation and will therefore induce modifications of the gut microbiota. We investigated variation in the gut bacteria through 16S rRNA metabarcoding, related to the genetic diversity of European mink held in captivity in two breeding centers representing separate breeding stocks originating from the western and eastern populations. The genetic diversity of the host was assessed through diversity analysis of the adaptive MHC class I and II genes as well as neutral microsatellite markers. Results indicate lower diversity in neutral and MHC class I genes for the western population, and the opposite for MHC class II. A lower MHC class II gene variability led to an increase in microbial phylogenetic diversity and in abundance depending on the presence of specific MHC-II motifs. This shows the importance of integrating both neutral and adaptive markers when investigating genetic variation in the context of ex situ conservation, as well as gut microbial community assessment. We advocate for more natural mating systems in captive breeding program to foster genetic diversity as a whole to mitigate the effects of genetic drift on those small, isolated populations.