Rationale The gut microbiota may play an important role in the development and functioning of the mammalian central nervous system. The assumption of the experiment was to prove that the use of probiotic bacterial strains in the diet of mice modifes the expression of brain proteins involved in metabolic and immunological processes. Objectives and results Albino Swiss mice were administered with Bifdobacterium longum Rosell®-175 or Lactobacillus rhamnosus JB-1 every 24 h for 28 days. Protein maps were prepared from hippocampal homogenates of euthanized mice. Selected proteins that were statistically signifcant were purifed and concentrated and identifed using MALDI-TOF mass spectrometry. Among the analysed samples, 13 proteins were identifed. The mean volumes of calcyon, secreted frizzledassociated protein 3, and catalase in the hippocampus of mice from both experimental groups were statistically signifcantly higher than in the control group. In mice supplemented with Lactobacillus rhamnosus JB-1, a lower mean volume of fragrance binding protein 2, shadow of prion protein, and glycine receptor α4 subunit was observed compared to the control. Conclusion The psychobiotics Bifdobacterium longum Rosell®-175 and Lactobacillus rhamnosus JB-1enhances expression of proteins involved in the activation and maturation of nerve cells, as well as myelination and homeostatic regulation of neurogenesis in mice. The tested psychobiotics cause a decrease in the expression of proteins associated with CNS development and in synaptic transmission, thereby reducing the capacity for communication between nerve cells. The results of the study indicate that psychobiotic bacteria can be used in auxiliary treatment of neurological disorders.