Causality relationship between 91 inflammatory factors and 5 intestinal diseases: A two-sample bidirectional Mendelian randomized study

Emerging evidence from recent pathological investigations has demonstrated that chronic inflammation plays a pivotal role in the pathogenesis of intestinal diseases, including inflammatory bowel disease (IBD), ulcerative colitis (UC), Crohn disease (CD), colorectal adenocarcinoma (CAC), and colorectal cancer (CRC). However, the precise regulatory mechanisms of inflammatory cytokines remain incompletely elucidated, and the causal relationships between inflammatory responses and intestinal diseases require further validation. This study employed a two-sample Mendelian randomization (MR) approach to comprehensively evaluate potential causal associations between 91 circulating inflammatory factors and these 5 intestinal diseases. MR analysis revealed a significant causal relationship between the levels of inflammatory factors C-C motif chemokine 19 and CD40L receptor and the risk of IBD. Furthermore, CD, UC and CRC respectively showed potential causal relationships with inflammatory factors C-C motif chemokine 20, Programmed cell death 1 ligand 1 and interleukin-5. No inflammatory factor showed a causal relationship with CAC. Reverse MR Analysis indicated that the progression of CRC could significantly regulate the expression level of the inflammatory factor Macrophage colony-stimulating factor 1. Unlike most previous studies that merely focused on the association between a certain inflammatory factor and intestinal diseases, this study was the first to systematically identify the relationships between 91 inflammatory factors and intestinal diseases based on the MR method. These results not only deepen our understanding of the inflammatory regulatory mechanism of intestinal diseases, but also provide a theoretical basis for the development of future clinical early diagnosis and targeted treatment strategies.