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

Area of Science:

• Gastroenterology and Microbiology
• Genetic Epidemiology

Background:

• Perianal abscess and anal fistula are painful surgical conditions with high recurrence rates, significantly impacting patient quality of life.
• Previous research suggests differences in gut microbiota composition in patients with these conditions, but causal links remain unclear.
• Understanding the gut microbiome's role is crucial for developing targeted treatments and prevention strategies.

Purpose of the Study:

• To investigate the potential causal relationships between specific gut microbiota taxa and the risk of developing perianal abscess and anal fistula.
• To differentiate the gut microbiome's influence on these two distinct but related surgical conditions.

Main Methods:

• Utilized bidirectional two-sample Mendelian randomization (MR) analysis.
• Leveraged gut microbiota data from the MiBioGen consortium and outcome data from the MRC IEU Open GWAS project.
• Employed the inverse variance weighted (IVW) method as the primary analysis, supported by sensitivity analyses for robustness.

Main Results:

• Four gut microbiota taxa were causally associated with perianal abscess risk: Eubacterium brachy group (increased risk), Ruminococcaceae UCG003, Erysipelatoclostridium, and Butyrivibrio (decreased risk).
• Eight gut microbiota taxa were significantly associated with anal fistula risk: Catenibacterium and Eubacterium ruminantium group (increased risk), while Haemophilus, Alloprevotella, Ruminiclostridium5, Erysipelotrichaceae UCG003, Butyrivibrio, and Escherichia-Shigella showed a protective effect.
• Sensitivity analyses confirmed the robustness of these findings, and reverse MR analyses ruled out reverse causality.

Conclusions:

• This study provides the first MR evidence of causal links between specific gut bacteria and perianal infections.
• Identified distinct gut microbial signatures associated with increased or decreased risk for perianal abscess and anal fistula.
• Findings enhance the understanding of the gut microbiome's role in the pathogenesis of these conditions, potentially informing future therapeutic approaches.