Mechanistic insights into pancreatic cancer progression from circadian rhythm disruption and gut microbiota dysbiosis (Review)

Pancreatic cancer has nearly doubled in incidence over the past two decades, becoming one of the deadliest types of malignancy in humans, with poor prognosis. With advances in modern medicine, the 5‑year survival rate for pancreatic cancer has increased from <5% in 1990 to ~10% in 2021. Most patients are diagnosed at an advanced stage, and ~20% of patients diagnosed at an early stage are eligible for surgical resection, with a 5‑year survival rate after surgery of up to 25%. With the aging population, the incidence of pancreatic cancer is expected to continue rising. The gut microbiota, a crucial ecosystem, comprises >1x10¹⁴ microorganisms that influence the development of pancreatic cancer through immune modulation and metabolites. Circadian rhythms, as a conserved molecular feedback loop, regulate cell metabolism and immune function, and their dysregulation is associated with metabolic disorders and tumor progression. Circadian rhythm disruption not only affects the gut microbiota and its metabolites but also accelerates pancreatic cancer progression through mechanisms such as promoting inflammation, immune suppression and drug resistance. The present review summarizes the impact of circadian rhythm dysregulation on the gut microbiota and its metabolites, specific microbiota associated with pancreatic cancer and their mechanisms in tumor progression and aims to deepen the understanding of the role of gut microbiota in pancreatic cancer treatment, providing a theoretical basis for future therapeutic strategies.