Evaluating the association between immunological proteins and common intestinal diseases using a bidirectional two-sample Mendelian randomization study

•Dysregulated immunological proteins contribute to intestinal diseases.•Bidirectional Mendelian randomization was used to assess causality.•Elevated IL-6 levels correlate with genetic predisposition to IBD.•Higher TNF-α levels are associated with increased colorectal cancer risk. Dysregulation of intestinal homeostasis, characterized by imbalanced immunological proteins, contributes to the pathogenesis of common intestinal diseases, e.g., irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and colorectal cancer (CRC). However, the potential causal relationships between specific immunological proteins and these diseases remain to be fully elucidated. In this study, we employed the bidirectional two-sample Mendelian randomization analysis to infer potential causal relationships between representative immunological proteins and these intestinal diseases. Genome-wide association study (GWAS) summary statistics of IBS, IBD, and CRC were obtained from public databases and utilized in MR analysis. Multiple sensitivity analyses were performed to evaluate the robustness, with p-values adjusted using the Benjamini-Hochberg method for multiple comparisons. Our findings revealed a significant association between IL-1β (OR = 0.783, 95 % CI: 0.676 to 0.908, adjusted P = 0.048) and a decreased risk of IBS. Furthermore, genetic predisposition to IBS was related to the reduced levels of IL-25 (β = − 0.233, 95 % CI: −0.372 to −0.094, adjusted P = 0.047). Additionally, genetic predisposition to IBD was correlated with elevated levels of IL-6 (β = 0.046, 95 % CI: 0.022–0.069, adjusted P = 0.010). The levels of TNF-α (OR = 1.252, 95 % CI: 1.102 to 1.423, adjusted P = 0.047) were associated with an increased risk of CRC. Our study suggests associations between specific immunological proteins and intestinal diseases, which would provide valuable insights for developing targeted immunomodulation therapies for these conditions. Further investigation into underlying mechanisms remains a research priority in the future.