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

🎖️ Top 10% JournalJan 30, 2026International journal of molecular medicine

How Disrupted Body Clocks and Gut Bacteria Imbalance May Influence Pancreatic Cancer Growth

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Abstract

The 5-year survival rate for pancreatic cancer has increased from <5% in 1990 to approximately 10% in 2021.

Pancreatic cancer incidence has nearly doubled in the past two decades, making it one of the deadliest malignancies.
Around 20% of patients diagnosed early are eligible for surgical resection, with a 5-year survival rate post-surgery reaching up to 25%.
Circadian rhythm disruption may accelerate pancreatic cancer progression by promoting inflammation, immune suppression, and drug resistance.
The gut microbiota, consisting of over 1 trillion microorganisms, could influence pancreatic cancer development through immune modulation and metabolites.
Dysregulation of circadian rhythms is associated with altered gut microbiota composition and its metabolites, affecting tumor progression.

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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 >1x10microorganisms 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. 14

Abstract

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