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

Area of Science:

• Gastroenterology and Immunology
• Genetics and Epidemiology

Background:

• Chronic inflammation is key in intestinal diseases like IBD, UC, CD, CAC, and CRC.
• Precise inflammatory cytokine mechanisms and causal links to intestinal diseases need more research.

Purpose of the Study:

• To investigate causal associations between 91 circulating inflammatory factors and 5 major intestinal diseases using Mendelian randomization.
• To systematically identify inflammatory factors linked to intestinal disease pathogenesis.

Main Methods:

• Employed a two-sample Mendelian randomization (MR) approach.
• Analyzed 91 circulating inflammatory factors against inflammatory bowel disease (IBD), ulcerative colitis (UC), Crohn disease (CD), colorectal adenocarcinoma (CAC), and colorectal cancer (CRC).
• Conducted reverse MR analysis to explore disease-to-factor relationships.

Main Results:

• Identified causal links between C-C motif chemokine 19, CD40L receptor, and IBD risk.
• Found potential causal relationships for CD, UC, and CRC with C-C motif chemokine 20, PD-L1, and IL-5, respectively.
• No inflammatory factor linked to CAC; CRC progression affects M-CSF1 expression.

Conclusions:

• This study systematically identified causal inflammatory factors for IBD, CD, UC, and CRC, advancing understanding of their pathogenesis.
• Results provide a foundation for developing novel early diagnostic markers and targeted therapies for intestinal diseases.
• Highlights the distinct inflammatory profiles associated with different intestinal diseases.