Department of Gastroenterology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China; Shaanxi Key Laboratory of Gastrointestinal Motility Disorders, Xi'an Jiaotong University, Xi'an, China; Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an, China; The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China.
Department of Gastroenterology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China; Shaanxi Key Laboratory of Gastrointestinal Motility Disorders, Xi'an Jiaotong University, Xi'an, China.
Cytokine. 2024 Dec;184:156788. doi: 10.1016/j.cyto.2024.156788. Epub 2024 Oct 29.
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.
肠道内稳态失调，其特征为免疫蛋白失衡，导致常见肠道疾病的发病机制，例如肠易激综合征（IBS）、炎症性肠病（IBD）和结直肠癌（CRC）。然而，特定免疫蛋白与这些疾病之间的潜在因果关系仍有待充分阐明。在本研究中，我们采用双向二样本孟德尔随机化分析来推断代表性免疫蛋白与这些肠道疾病之间的潜在因果关系。IBS、IBD 和 CRC 的全基因组关联研究（GWAS）汇总统计数据从公共数据库中获得，并用于 MR 分析。采用多种敏感性分析来评估稳健性，对多重比较进行了 Benjamini-Hochberg 方法调整的 P 值校正。我们的研究结果表明，IL-1β（OR = 0.783，95%CI：0.676 至 0.908，调整 P = 0.048）与 IBS 风险降低之间存在显著关联。此外，IBS 的遗传易感性与 IL-25 水平降低有关（β= -0.233，95%CI：-0.372 至 -0.094，调整 P = 0.047）。此外，IBD 的遗传易感性与 IL-6 水平升高相关（β=0.046，95%CI：0.022 至 0.069，调整 P = 0.010）。TNF-α 水平（OR = 1.252，95%CI：1.102 至 1.423，调整 P = 0.047）与 CRC 风险增加相关。我们的研究表明特定免疫蛋白与肠道疾病之间存在关联，这为针对这些疾病的靶向免疫调节治疗提供了有价值的见解。未来仍需进一步研究潜在机制。
