Gut microbiota and perianal abscess and anal fistula: A bidirectional Mendelian randomization study

Perianal abscess and anal fistula are debilitating surgical conditions characterized by severe pain, persistent pus discharge, and prolonged recovery periods with high recurrence rates, collectively imposing profound burdens on patients' quality of life, social functioning, and work productivity. Research has indicated potential distinction regarding the composition of gut microbiota in patients suffering from perianal abscess and anal fistula. The causal effect is yet unclear. The MiBioGen consortium was utilized to acquire data pertaining to gut microbiota, while the outcome data was provided by another project called the MRC Integrative Epidemiology Unit Open Genome-wide Association Studies (IEU Open GWAS) project. We performed bidirectional two-sample Mendelian randomization (MR) using inverse variance weighted (IVW) as the primary method, selected for its robustness to balanced pleiotropy when valid instrumental variables are used. Additionally, sensitivity analyses were conducted to examine the robustness of the results. Four gut microbiota taxa showed causal associations with perianal abscess risk: Eubacterium brachy group (OR = 1.41, P = .004), Ruminococcaceae UCG003 (OR = 0.61, P = .007), Erysipelatoclostridium (OR = 0.68, P = .009), and Butyrivibrio (OR = 0.81, P = .016). For anal fistula, 8 taxa were significant: Catenibacterium (OR = 1.22, P = .042) and Eubacterium ruminantium group (OR = 1.17, P = .013) increased risk, while Haemophilus (OR = 0.79, P = .005), Alloprevotella (OR = 0.78, P = .001), Ruminiclostridium5 (OR = 0.79, P = .019), Erysipelotrichaceae UCG003 (OR = 0.82, P = .034), Butyrivibrio (OR = 0.88, P = .006), and Escherichia-Shigella (OR = 0.82, P = .039) conferred protection. Furthermore, the findings from the sensitivity analyses demonstrate robust stability in these conclusions. Reverse MR analyses did not suggest reverse causality. This is the first MR investigation into the causal relationships between the onset of perianal infections and particular taxa of the gut microbiota. It enhances our comprehension of the correlation.