Contribution of gut microbiome to pancreatic ductal adenocarcinoma development

Over the past decade, significant progress has been made in understanding the role of microbiota as an ecosystem that functions as a separate organ in a macroorganism. It is known that disturbances in the intestinal microflora affect the pathogenesis and progression of many human diseases. In particular, in gastrointestinal oncology, the gut microbiota affects tumor growth due to dysbiosis, the release of bacterial toxins, and the modulation of cell signaling pathways. Recent studies indicate that the intestinal microbiome plays an important role in the pathogenesis of pancreatic ductal adenocarcinoma, affecting carcinogenesis, immune response, and treatment efficacy. For example, such microorganisms as Porphyromonas gingivalis and Fusobacterium nucleatum are involved in oncogenesis by modulating the tumor microenvironment and stimulating immune responses, which promotes tumor growth, metastasis, and resistance to therapy. In addition, the involvement of kynurenine pathway metabolites (kynurenine, quinolinic acid, and 3-hydroxyanthranilic acid) in cancer has been previously investigated. The current review attempts to clarify the role of bacterial metabolites such as trimethylamine oxide and lipopolysaccharide in influencing antitumor immunity, suggesting potential targets for enhancing the response to immunotherapy. Implementation of microbiome research findings into clinical practice is an emerging field. Personalized therapy for pancreatic cancer is possible through understanding and manipulating the microbiome, which requires further research to develop optimal therapeutic strategies and evaluate combination approaches.