Abstract:Pancreatic cancer (PC) is highly malignant, with an insidious onset and poor prognosis. Current treatments often lead to recurrence and resistance due to the immunosuppressive characteristics of the tumor microenvironment (TME). The TME frequently affects the efficacy of tumor immunotherapy, particularly in suppressive immune microenvironments where tumor immune escape and immune tolerance occur. The microbiome, as a bridge between the host and the environment, has been shown to play an important regulatory role in tumor immune responses. By targeting specific microbiota to regulate immune cell functions, the therapeutic effects of immune checkpoint inhibitors can be enhanced. This article focuses on the immune microenvironment of pancreatic cancer, reviewing the research progress on the microbiome"s role in influencing the PC immune microenvironment and enhancing immunotherapy efficacy through differential analysis of gastrointestinal tumor-associated microbiomes. It also analyzes the effectiveness of improving the suppressive immune microenvironment of PC by intervening in the microbiome and its metabolic pathways, and discusses the regulatory mechanisms of the microbiome in PC immune responses, with the aim of providing new personalized immunotherapy strategies for PC patients.