Strategic modulation of the gastrointestinal microbiome to enhance pancreatic cancer immunotherapy.

Pancreatic cancer (PC) remains one of the most lethal malignancies, characterized by aggressive progression, late detection, and limited response to current therapies. Recent research has revealed that the gastrointestinal and intratumoral microbiomes are key modulators of immune regulation, metabolism, and epigenetic pathways, influencing tumor progression and therapeutic efficacy. This review summarizes the complex microbiome-PC interplay, emphasizing microbial modulation of inflammation, immunity, and treatment resistance. We also highlight microbiome-targeted strategies, such as probiotics, prebiotics, postbiotics, and fecal microbiota transplantation, along with advanced drug-delivery platforms - including nanoparticles, engineered bacteria, and stimuli-responsive systems - for precise microbiome modulation. Integrating microbiome science with immunotherapy, nanotechnology, and epigenetic reprogramming offers promising opportunities to improve outcomes in PC.