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Published on: February 28, 2018
Causal effect between gut microbiota and pancreatic cancer: a two-sample Mendelian randomization study
Zhichen Jiang1, Yiping Mou2,3, Huiju Wang2,3
1The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, China.
Background:
Gut microbiota (GM) comprises a vast and diverse community of microorganisms, and recent studies have highlighted the crucial regulatory roles of various GM and their secreted metabolites in pancreatic cancer (PC). However, the causal relationship between GM and PC has yet to be confirmed.
Methods:
In the present study, we used two-sample Mendelian randomization (MR) analysis to investigate the causal effect between GM and PC, with genome-wide association study (GWAS) from MiBioGen consortium as an exposure factor and PC GWAS data from FinnGen as an outcome factor. Inverse variance weighted (IVW) was used as the primary method for this study.
Results:
At the genus level, we observed that Senegalimassilia (OR: 0.635, 95% CI: 0.403-0.998, P = 0.049) exhibited a protective effect against PC, while Odoribacter (OR:1.899, 95%CI:1.157-3.116, P = 0.011), Ruminiclostridium 9(OR:1.976,95%CI:1.128-3.461, P = 0.017), Ruminococcaceae (UCG011)(OR:1.433, 95%CI:1.072-1.916, P = 0.015), and Streptococcus(OR:1.712, 95%CI:1.071-1.736, P = 0.025) were identified as causative factors for PC. Additionally, sensitivity analysis, Cochran's Q test, the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO), and MR-Egger regression indicated no heterogeneity, horizontal pleiotropy, or reverse causality between GM and PC.
Conclusions:
Our analysis establishes a causal effect between specific GM and PC, which may provide new insights into the potential pathogenic mechanisms of GM in PC and the assignment of effective therapeutic strategies.
Insights
This study reveals a causal link between specific gut bacteria and pancreatic cancer (PC). Certain bacteria like Senegalimassilia may protect against PC, while others such as Odoribacter and Streptococcus increase risk.
Area of Science:
- Microbiology
- Genetics
- Oncology
Background:
- Gut microbiota (GM) plays a regulatory role in pancreatic cancer (PC).
- The causal relationship between GM and PC remains unconfirmed.
- Microbial metabolites are increasingly recognized for their influence on PC development.
Purpose of the Study:
- To investigate the causal effect of gut microbiota on pancreatic cancer.
- To identify specific bacterial genera associated with PC risk.
- To leverage Mendelian randomization for causal inference.
Main Methods:
- Two-sample Mendelian randomization (MR) analysis was employed.
- Genome-wide association study (GWAS) data from MiBioGen (exposure) and FinnGen (outcome) were utilized.
- Inverse variance weighted (IVW) method served as the primary analytical approach.
Main Results:
- Senegalimassilia showed a protective effect against PC (OR: 0.635, P=0.049).
- Odoribacter, Ruminiclostridium 9, Ruminococcaceae (UCG011), and Streptococcus were identified as risk factors for PC.
- Sensitivity analyses confirmed no significant heterogeneity, horizontal pleiotropy, or reverse causality.
Conclusions:
- Specific gut microbiota genera have a causal effect on pancreatic cancer.
- These findings offer insights into PC pathogenesis.
- Potential therapeutic strategies targeting GM for PC may be developed.
