Background: Recent studies have demonstrated that commensal, probiotic, and pathogenic bacteria in the gastrointestinal tract can activate central nervous system (CNS) signaling systems, possibly through neural, endocrine and immune pathways, thus influencing brain function and behavior. This emerging concept of the microbiome–gut–brain axis suggests modulation of the gut microbiome as a potential novel therapeutic strategy for CNS disorders. In our laboratory, we selectively bred mice, from the WT sabra strain, with strong features of dominance (Dom) and submissiveness (Sub) that represent opposite poles of the behavioral spectrum. We hypothesized that Dom and Sub mice with opposing behavioral phenotypes may possess differential gut microbiomes and that modulation of the gut microbiome may alter depressive-like behavior. Results: Using 16S rRNA gene sequencing, we found Dom and Sub mice`s gut microbiome to be comprised of significantly different ratios between bacterial phyla, attributed mainly to Bacteroidetes and Firmicutes. At the same time, the gut microbiome of WT mice, which represent a heterogeneous population displaying a mixed behavioral profile, was found to include Facteroidetes and Firmicutes bacteria, at a ratio approximately the average between that of Dom and Sub mice. WT sabra mice, transplanted with Sub and Dom-associated gut microbiota, exhibited changes in depressive-like behavior. Conclusions: Dom and Sub mice may be used for further investigation of the effects of the gut microbiome upon behavior. Targeted modulation of the microbiome may induce behavioral changes, leading to a better understanding of the role of the microbiome–gut–brain axis upon behavior.