Exploring the causality between gut microbiota and esophageal carcinoma: a two-sample Mendelian randomization analysis

Abstract

Abstract Background Esophageal cancer is a common tumor of upper gastrointestinal tract. However, the increasing evidence indicates that gut microbiota are closely related to the occurrence and development of esophageal cancer, the causal association between gut microbiota and esophageal cancer remains to be determined. As a consequence, in this paper, a two-sample Mendelian randomization analysis was used to evaluate and explore the causal relationship between gut microbiota and the risk of esophageal cancer, and identify specific pathogenic bacterial taxa. Methods Genetic instrumental variables for gut microbiota were identified from a genome-wide association study (GWAS) of 18,340 participants, esophageal cancer as the outcome variable was identified from a GWAS including 1091 cases and 410,350 controls. Using the inverse variance weighted (IVW) method as the primary analysis, and further (using) the weighted median method, MR-Egger regression, MR multi-directional residuals, and outlier tests were further performed to improve the robustness of the results. Results The IVW results showed that genus.DefluviitaleaceaeUCG011 (OR = 3.124, 95%CI 1.388–7.031, P = 0.006), genus.LachnospiraceaeUCG008 (OR = 3.964,95%CI 1.463–10.740, P = 0.007), family.Pasteurellaceae.id.3689(OR = 2.022, 95%CI 1.046 − 3.909, P = 0.036)and order.Pasteurellales.id.3688༈OR = 2.022, 95%CI1.046 − 3.909, P = 0.036༉showing a positive causal relationship between gut microbiota and esophageal cancer.Conversely,genus.Peptococcus(OR = 0.525, 95% CI 0.286–0.961,P = 0.037) ,genus.Ruminiclostridium5(OR = 0.117,95%CI0.0310.442,P = 0.002),genus.RuminococcaceaeUCG009 ༈OR = 0.350, 95%CI 0.157 − 0.777, P = 0.01༉and genus.Ruminococcus1༈OR = 0.341, 95%CI 0.118 − 0.985, P = 0.047༉showed a negative causal relationship with esophageal cancer. No significant heterogeneity was found in the instrumental variable or horizontal pleiotropy. Conclusions Our MR analysis study revealed that the gut microbiota was causally associated with esophageal cancer and the risk of esophageal cancer, and also identified eight bacterial taxa with a causal relationship with the development and progression of esophageal cancer.That may be useful in providing new insights for further mechanistic and clinical studies of microbiota-mediated cancer.