Deciphering the gut microbiota's role in diverticular disease: insights from a Mendelian randomization study

Abstract

Background: Previous studies have indicated a potential association between gut microbiota and diverticular disease. However, the precise nature of this relationship remains unclear. In light of this, we decided to use a bidirectional two-sample Mendelian randomization (MR) study to investigate the causal relationship between gut microbiota and intestinal diverticular disease in greater depth.

Methods: To investigate the potential causal relationship between gut microbiota and intestinal diverticular disease, we conducted a two-sample MR study in a European ancestry. Genetic instrumental variables for gut microbiota were obtained from a genome-wide association study (GWAS) involving 5,959 participants. Summary statistics for intestinal diverticular disease were sourced from the IEU Open GWAS project, which included data from 5,193 cases and 457,740 controls. The analysis was primarily conducted using the inverse variance weighted method, with additional sensitivity analyses to assess the robustness of the findings.

Results: With regard to the findings, 11 microbial taxa were identified as having a potential causal relationship with intestinal diverticular disease. Specifically, the microbial taxa Caryophanales, Paenibacillaceae, Herbinix, Turicibacter, Turicibacteraceae, and Staphylococcus fleurettii were found to be positively associated with the risk of developing intestinal diverticular disease, while Chromatiales, Arcobacter, Herbidospora, Ligilactobacillus ruminis, and Megamonas funiformis were found to be negatively associated with the risk. Further reverse MR analysis did not reveal a reverse causal effect between these microbial taxa and intestinal diverticular disease.

Conclusion: Our MR analyses revealed a potential causal relationship between certain gut microbiota and intestinal diverticular disease, which may provide new directions for future intestinal diverticular disease prevention and treatment strategies.

Keywords: GWAS; Mendelian randomization; diverticular disease; gut microbiota; instrumental variables.