Proliferative and Transcriptomic Response of Experimental B16-F10 Melanoma to Modulation of Murine Microbiota by Oral Administration of Lacticaseibacillus Rhamnosus K32 and Bifidobacterium Adolescentis 150

Background. Recent research is actively studying the effect of probiotics on the immune system and their potential in the complex therapy of oncologic diseases. It has been found that probiotics are able to modulate the immune response by interacting with the intestinal microbiota, which can increase the effectiveness of immunotherapy and reduce the side effects of chemotherapy and radiation therapy. In particular, some strains have demonstrated the ability to suppress chronic inflammation and enhance antitumor immunity, but their clinical application requires additional research. The Aim was to study the effect of oral administration of probiotic strains Lacticaseibacillus rhamnosus K32 and Bifidobacterium adolescentis 150 on the growth and gene expression of model melanoma B16-F10, as well as on the structure of the microbiota of experimental animals. Results. The study revealed significant differences in the effect of the studied probiotic strains on the development of melanoma B16-F10. B. adolescentis 150 strain significantly stimulated the growth of tumor mass (corr. p = 0.02 compared to control and p = 0.001 relative to L. rhamnosus K32 group). At the molecular level in melanoma cells, this was accompanied by suppression of the interferon response, activation of proliferative signaling pathways (WNT/β-catenin, TGF-β) and decreased expression of immune cell markers. In contrast, L. rhamnosus strain K32 had no statistically significant effect on tumor growth rate (p = 0.4), but caused increased expression of markers of cytotoxic T lymphocytes and NK cells, as well as activation of the interferon response. Both tested strains caused significant changes in the composition of the intestinal microbiota, characterized by an increase in the relative abundance of bacteria of the Klebsiella genus, and induced activation of pro-inflammatory signaling pathways (NF-κB, IL-6/JAK/STAT3, IL-2/STAT5) in tumor tissue. Importantly, the use of both probiotics was associated with activation of epithelial-mesenchymal transition processes and hypoxia in the tumor, which may create favorable conditions for its progression and metastasis. Conclusions. The findings emphasize the complex and ambiguous effects of probiotics on oncogenesis and the need for careful strain selection for adjuvant therapy of melanoma and other cancers.