Causal effect between gut microbiota and pancreatic cancer: a two-sample Mendelian randomization study

Abstract

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.

The Causal Association between Gut Microbiota and Pancreatic Cancer: A Two-sample Mendelian Randomization Analysis in European and East Asian Populations

“…However, these findings varied from the results obtained from biobanks in the UK and Japan. [29,30]. All this evidence suggested that the PC-related gut microbiota signatures varied across different popula/ons.…”

Impact of the Mediterranean Diet on the Gut Microbiome of a Well-Defined Cohort of Healthy Individuals

“…The first three have been related to inflammatory bowel disease and cirrhotic patients with hepatocellular carcinoma [ 63 , 81 ]; however, Dialister is decreased in patients with gastric cancer [ 68 ]. With respect to a negative correlation with glucose, we found genera related to good health or even protective against some diseases, such as pancreatic cancer [ 67 , 82 ], but we also found Olsenella , which is more related to an increase in diseases such as ulcerative colitis [ 78 ].…”

“…Finally, concerning the genera that correlated positively with red meat consumption, we found genera related to inflammatory bowel disease, such as Faecalicoccus and Clostridium sensu stricto [ 62 , 63 ]; Anaerofustis , which is related to ulcerative colitis but also to greater longevity [ 63 , 83 ]; and other genera that are more related to a good state of health, such as Phascolarctobacterium and Subdoligranulum [ 69 , 84 ]. The genera found to be inversely correlated with red meat consumption were mostly related to anti-inflammatory function, protection against some types of cancer, or low risk of celiac disease [ 82 , 85 , 86 ].…”

Assessing the causal relationship between gut microbiota and prostate cancer: a two-sample Mendelian randomization study

“…To the best of our knowledge, among the 12 gut microbial taxa identi ed as potentially causally related to PCa, a few are associated with other cancers or diseases, while the majority have been rarely reported or are even absent in previous studies on PCa. A recent MR study suggested that the genus Odoribacter is a risk factor for pancreatic cancer, and a causal relationship has been established 42 . Moreover, in patients with hepatocellular carcinoma, an increased abundance of the genus Odoribacter was observed in the intestine 43 .…”