Investigating the Causal Association between Intestinal Microbiota and Esophageal Diseases Using Two-Sample Mendelian Randomization

Abstract

Objective: Using the Mendelian randomization approach with two-sample analysis, this study explores the causal relationship between gut microbiota and esophageal diseases, providing valuable biomarkers for early disease diagnosis and potential therapeutic targets for esophageal diseases. Methods: Genomewide association data were analyzed with gut microbiota at the genus level as the exposure variable and esophageal diseases (Barrett's esophagus, gastroesophageal reflux disease, esophageal cancer, esophagitis) as the outcome variables. Mendelian randomization analysis was conducted using inverse variance weighted, weighted median, MR-Egger, simple mode, and weighted mode methods. Outlier tests, heterogeneity tests, sensitivity analyses, Pleiotropic analyses, and the removal of single nucleotide polymorphisms with confounding factors were performed. Results: Three genera (Eubacterium eligens group, Actinomyces, Clostridium sensu stricto 1) were protective against Barrett's esophagus, while six genera (Oxalobacter, Allisonella, Ruminococcaceae UCG009, Haemophilus, Sutterella, Anaerostipes) were risk factors for Barrett's esophagus. Two genera (Lachnospiraceae UCG004, Methanobrevibacter) were protective against gastroesophageal reflux disease, and two genera (Prevotella 9, Anaerostipes) were risk factors for gastroesophageal reflux disease. Three genera (Coprococcus 1, Bilophila, Candidatus Soleaferrea) were protective against esophageal cancer, while six genera (Coprobacter, Catenibacterium, Eubacterium coprostanoligenes group, Marvinbryantia, Sutterella, Ruminococcaceae UCG010) were risk factors for esophageal cancer. Two genera (Parasutterella, Howardella) were protective against esophagitis. Conclusion: Our study utilizes genetic prediction to identify specific GMs and establishes the causal relationship between them, potentially providing valuable biomarkers for early disease diagnosis and potential therapeutic targets for the four esophageal diseases mentioned above.