Notably, our mediation MR results suggest interleukin-1 receptor type 2 (IL-1R2) as a mediator for the effect of the genus Clostridium innocuum group on hypertension, accounting for a mediation proportion of 14.07% [mediation effect: (b = 0.0007, 95%CI: 0.0002–0.0011); proportion mediation = 14.07% (4.26–23.40%)]. This evidence concerns the gene IL1R2 and hypertensive disorder.