Gut microbiota and pancreatic cancer: tumorigenesis, progression, and clinical applications

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies of the digestive system, with a 5-year survival rate of only 13%, which is largely due to late-stage diagnosis and limited therapeutic options. Emerging evidence indicates that the gut microbiota has a critical role in PDAC tumorigenesis, progression, and therapeutic response. This review comprehensively summarizes current insights into gut microbiota-PDAC interactions, highlighting microbial alterations across taxonomic, functional, and clinical dimensions. Gut dysbiosis, which is marked by depletion of beneficial species and enrichment of pathogenic taxa, contributes to carcinogenesis through chronic inflammation, immune dysregulation, and metabolic reprogramming. In particular, the loss of butyrate-producing bacteria reduces anti-inflammatory activity and weakens CD8⁺ T cell function, thereby promoting tumor development. In addition to initiation, the gut microbiota also shapes PDAC progression through direct translocation to pancreatic tissue and systemic regulation of the tumor microenvironment (TME), influencing immune cell dynamics and fostering therapeutic resistance. Clinically, distinct microbial signatures are emerging as potential diagnostic and prognostic biomarkers. Moreover, microbiota-targeted interventions, including probiotics, synbiotics, fecal microbiota transplantation (FMT), metabolite supplementation, and dietary modulation, show promise as adjunctive therapeutic strategies. However, significant challenges remain in defining causal mechanisms and translating these findings into practice. Future research should integrate multi-omics profiling with well-designed clinical trials to delineate the gut microbiota-PDAC interaction network, guide precision microbiota-based interventions, and ultimately enable earlier detection and personalized treatment of this lethal disease.