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Stem cells play a critical role in the initiation, progression, and resistance of PDAC due to their plasticity, self-renewal capabilities, and ability to drive tumorigenesis. The gut microbiome, a diverse ecosystem of microorganisms, has a profound influence on systemic health, including the development of cancer. Recent studies have highlighted that the microbiome composition within the tumor can modulate stem cell behavior by shaping the tumor microenvironment (TME), enhancing cellular plasticity, and promoting the stemness properties of PDAC. 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