Nutrition-Gut Microbiota Axis in PDAC: Research Progress from Nutritional Abnormalities and Microbial Dysbiosis to Clinical Interventions

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with insidious onset and poor overall prognosis, representing one of the most challenging tumors in the digestive system. In recent years, advances in tumor nutrition, gut microbiome research, and immuno-metabolic studies have led to the recognition of PDAC as a systemic disease. It is driven not only by local tumor changes but also by host nutritional status, pancreatic exocrine and endocrine dysfunction, systemic inflammation, intestinal barrier integrity, and microbial dysbiosis. Patients with PDAC commonly experience weight loss, sarcopenia, cachexia, micronutrient deficiencies, and disturbances in glucose and lipid metabolism. These changes arise from multiple factors, including inadequate dietary intake, impaired digestion and absorption, pancreatic exocrine insufficiency, persistent inflammation, metabolic reprogramming, and treatment-related effects. At the same time, PDAC patients show clear alterations in gut microbiota composition and function, including reduced microbial diversity, loss of beneficial symbiotic bacteria, overgrowth of opportunistic pathogens, and impaired short-chain fatty acid metabolism. Nutritional abnormalities and microbial dysbiosis are not separate phenomena; they interact closely through the nutrition-gut microbiota axis and together contribute to PDAC development, treatment response, and clinical outcomes. As a result, nutritional assessment, body composition analysis, composite nutritional/immunological scores, and specific nutrition-related biomarkers are gaining importance for risk stratification and prognosis. Perioperative nutritional support, pancreatic enzyme replacement therapy, targeted nutrient interventions, and microbiota-directed strategies have also demonstrated promising clinical potential. This review summarizes changes in nutritional status and gut microbiota in PDAC, the value of nutrition-related biomarkers, and current intervention strategies targeting the nutrition-gut microbiota axis, to support more precise assessment and integrated management of the disease.