Gut microbiota, human blood metabolites and esophageal cancer: a Mendelian randomization study

Abstract Background: Unbalances in the gut microbiota have been proposed as a possible cause of esophageal cancer, yet the exact causal relationship remains unclear. Objectives: To investigate the potential causal relationship between the gut microbiota and esophageal cancer with Mendelian randomization (MR) analysis. Methods: Genome-wide association studies (GWAS) of 207 gut microbial taxa (5 phyla, 10 classes, 13 orders, 26 families, 48 genera, and 105 species) and 205 gut microbiota metabolic pathways conducted by the Dutch Microbiome Project (DMP) and a FinnGen cohort GWASs of esophageal specified the summary statistics. To investigate the possibility of a mediation effect between the gut microbiota and esophageal cancer, mediation MR analyses were performed for 1,091 blood metabolites and 309 metabolite ratios. Results: MR analysis indicated that the relative abundance of 10 gut microbial taxa was associated with esophageal cancer but all the 12 gut microbiota metabolic pathways with esophageal cancer indicated no statistically significant association existing. Two blood metabolites and a metabolite ratio were discovered to be mediating factors in the pathway from gut microbiota to esophageal cancer. Conclusion: This research indicated the potential mediating effects of blood metabolites and offered genetic evidence in favor of a causal correlation between gut microbiota and esophageal cancer.