Abstract
Background
Inflammatory bowel disease (IBD), a chronic inflammatory condition, is caused by several factors involving aberrant immune responses. Genetic factors are crucial in the occurrence of IBD. Mendelian randomization (MR) can offer a new perspective in understanding the genetic background of IBD.
Methods
The two-sample MR approach was used to estimate the causal relationship of immune cells to IBD. Single nucleotide polymorphisms (SNPs) were considered instrumental variables (IVs). We analyzed the relationship between 731 immunophenotypes, 1,400 metabolite phenotypes, and IBD.
Results
We identified the causal effects of HLA-DR-expressing CD14 + monocytes on IBD through MR analysis. The phenotype of "HLA-DR expression on CD14 + monocytes" showed the strongest association among the selected 48 immune phenotypes. Chiro-inositol metabolites mediate the effect of CD14 + monocytes expressing HLA-DR on IBD. An increase in Chiro-inositol metabolites was associated with a reduced risk of IBD occurrence, accounting for 4.97%.
Conclusion
Our findings reveal a new pathway by which HLA-DR-expressing CD14 + monocytes indirectly reduce the risk of IBD occurrence by increasing the levels of Chiro-inositol metabolites, providing a new perspective on the immunoregulatory mechanisms underlying IBD. It lays a theoretical foundation for developing new therapeutic targets.