The gut microbiota is a complex ecosystem, affected by both environmental factors and host genetics. Here we aim at uncovering the bacterial taxa whose gut persistence is controlled by host genetic variation. We used a murine model based on inbred lines BALB/c and C57BL/6J and their F1 reciprocal hybrids (♀C57BL/6J×♂BALB/c; ♀BALB/c×♂C57BL/6J). To guarantee genetic similarity of F1, including the sex chromosomes, we used only female mice. Based on 16S rRNA genes sequencing, we found that the genetically different inbred lines present different microbiota, whereas their genetically identical F1 reciprocal hybrids presented similar microbiota. Moreover, the F1 microbial composition differed from that of both parental lines. Twelve taxa were shown to have genetically controlled gut-persistence, while none were found to show maternal effects. Nine of these taxa were dominantly inherited by C57BL/6J line. Co-housing of the parental inbred lines resulted in a temporary and minor shift in microbiota composition, which returned back to the former microbial composition following separation, indicating that each line tends to maintain a unique bacterial signature reflecting the line. Taken together, our findings indicate that mouse genetics has an effect on the microbial composition in the gut, which is greater than maternal effect and continuous exposure to the alternative line different microbiota. Uncovering the bacterial taxa associated with the host’s genetics and understanding their role in the gut ecosystem could lead to development of genetically-oriented probiotic products, as part of the personalized medicine approach.