Causal associations between human gut microbiota and hemorrhoidal disease: A two-sample Mendelian randomization study

Area of Science:

• Gastroenterology and Microbiology
• Human Genetics and Epidemiology

Background:

• Hemorrhoidal disease (HEM) is a prevalent condition with an unclear link to the gut microbiome.
• Understanding the causal relationship between gut bacteria and HEM is crucial for developing effective treatments.

Purpose of the Study:

• To investigate the potential causal associations between specific gut microbiota taxa and hemorrhoidal disease using a Mendelian randomization approach.

Main Methods:

• Utilized summary statistics from a large gut microbiome GWAS (MiBioGen Consortium, n=18,340) for exposure data.
• Employed European ancestry HEM case (n=218,920) and control (n=725,213) data from the European Bioinformatics Institute.
• Performed two-sample Mendelian randomization analyses with inverse-variance weighting, MR-Egger, MR-PRESSO, simple mode, and weighted median methods, including reverse causality analysis.

Main Results:

• Identified potentially protective effects of phylum Cyanobacteria, genus Phascolarctobacterium, and family FamilyXI on HEM risk.
• Found potentially detrimental effects of genus Ruminococcaceae_UCG_002, family Peptostreptococcaceae, genus Oscillospira, family Alcaligenaceae, and order Burkholderiales on HEM risk.
• Observed a reverse causal relationship between HEM and genus Oscillospira.

Conclusions:

• This is the first Mendelian randomization study to suggest specific causal links between gut microbiota and hemorrhoidal disease.
• Findings provide novel insights into the gut microbiome's role in HEM pathogenesis, potentially guiding future therapeutic strategies.