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

Hemorrhoidal disease (HEM) is a common condition affecting a significant proportion of the population. However, the causal relationship between the gut microbiota and hemorrhoids remains unclear. In this study, we employed a Mendelian randomization (MR) approach to investigate the potential associations between them. In this study, the exposure factor was determined by selecting summary statistics data from a large-scale gut microbiome whole-genome association study conducted by the MiBioGen Consortium, which involved a sample size of 18, 340 individuals. The disease outcome data consisted of 218, 920 cases of HEM and 725, 213 controls of European ancestry obtained from the European Bioinformatics Institute dataset. Two-sample MR analyses were performed to assess the causalities between gut microbiota and hemorrhoids using various methods, including inverse-variance weighting, MR-Egger regression, MR Pleiotropy Residual Sum and Outlier (MR-PRESSO), simple mode, and weighted median. Reverse MR analyses were performed to examine reverse causal association. Our findings suggest phylum Cyanobacteria (OR = 0. 947, 95% CI: 0. 915–0. 980, P = 2. 10 × 10 − 3), genus Phascolarctobacterium (OR = 0. 960, 95% CI: 0. 924–0. 997, P =. 034) and family FamilyXI (OR = 0. 974, 95% CI: 0. 952–0. 997, P =. 027) have potentially protective causal effects on the risk of HEM, while genus RuminococcaceaeUCG₀02 (OR = 1. 036, 95% CI: 1. 001–1. 071, P =. 042), family Peptostreptococcaceae (OR = 1. 042, 95% CI: 1. 004–1. 082, P =. 029), genus Oscillospira (OR = 1. 048, 95% CI: 1. 005–1. 091, P =. 026), family Alcaligenaceae (OR = 1. 048, 95% CI: 1. 005–1. 091, P =. 036) and order Burkholderiales (OR = 1. 074, 95% CI: 1. 020–1. 130, P = 6. 50 × 10 −3) have opposite effect. However, there was a reverse causal relationship between HEM and genus Oscillospira (OR = 1. 140, 95% CI: 1. 002–1. 295, P =. 046) This is the first MR study to explore the causalities between specific gut microbiota taxa and hemorrhoidal disease, which may offer valuable insights for future clinical interventions for hemorrhoidal disease.