Gut microbiota linked to pancreatic cancer risk in bidirectional MR study

A groundbreaking bidirectional Mendelian randomization (MR) study made available online on June 12, 2025, and published in Volume 9, Issue 1 of the Journal of Pancreatology on March 1, 2026, has uncovered causal relationships between gut microbiota and pancreatic cancer (PC), offering new insights into PC pathogenesis and potential therapeutic targets.

PC remains one of the deadliest digestive system cancers, with a 5-year survival rate below 10% due to late diagnosis, rapid progression, and limited treatment options. While observational studies have noted correlations between gut microbiota and PC, this research is the first to systematically explore their bidirectional causality using large-scale genome-wide association study data from European populations.

Analyzing data from 7,738 participants for 207 gut microbiota species and 314,924 individuals for PC, the team identified eight microbial species with direct causal links to PC risk. Three species—Parabacteroides merdae, Ruminococcus lactaris, and unclassified Veillonella—were associated with reduced PC risk. Conversely, five species—Bacteroides coprocola, Bacteroides finegoldii, Bacteroides fragilis, Prevotella copri, and unclassified Holdemania—emerged as potential PC risk factors.

The study also revealed that PC progression significantly alters gut microbiota composition. Seven microbial species, including Akkermansia muciniphila and R. lactaris, decreased in abundance during PC progression, while two species—P. merdae and Lachnospiraceae bacterium 1_1_57FAA—increased. Notably, a bidirectional relationship exists between P. merdae, R. lactaris, and PC, suggesting these microbes could serve as screening or therapeutic targets.

The research leveraged five analytical methods, with inverse variance weighted as the primary approach, and rigorous sensitivity analyses to exclude false-positive results from pleiotropy. The findings support the “gut-pancreas axis” theory, where gut microbiota influence PC development through metabolic regulation and immune response modulation, while PC disrupts gut microbial balance via metabolic disorders and immune suppression.

Senior author Professor Weibin Wang, from Peking Union Medical College Hospital, China, emphasized the study’s clinical implications: “Our findings highlight gut microbiota’s potential as biomarkers for early PC diagnosis and targets for intervention. Modulating specific microbial species could help prevent PC or improve treatment outcomes.”

Despite its strengths, the study has limitations, including exclusive reliance on European ancestry data and lack of multiple testing corrections. Future research will validate these findings in multi-ethnic cohorts and explore the molecular mechanisms underlying microbiota-PC interactions.

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Reference
DOI: 10.1097/JP9.0000000000000231

About Dr. Wang Weibin from Peking Union Medical College Hospital, China
Dr. Wang Weibin is a Chief Physician and Professor of General Surgery at Peking Union Medical College Hospital, China. He specialises in pancreatic cancer, minimally invasive surgery, and the diagnosis and treatment of pancreatic, biliary, gastrointestinal, thyroid, splenic, and retroperitoneal diseases. Dr. Wang completed postdoctoral research at the Technical University of Munich and currently serves as an Executive Deputy Director of the Department of General Surgery. His research focuses on early diagnosis and comprehensive treatment strategies for pancreatic cancer. He also holds leadership roles in several pancreatic associations across China.

Funding Information
WW received support from the National High Level Hospital Clinical Research Funding (Nos. 2022-PUMCH-D-001, 2022-PUMCH-B-004), the Capital’s Funds for Health Improvement and Research, CFH (2024-2-4017), the National Natural Science Foundation of China (No. 82173074), the Beijing Natural Science Foundation (No. 7232127), and the CAMS Innovation Fund for Medical Sciences (CIFMS) (No. 2021-I2M-1-002).