Gut microbiota causally affects ulcerative colitis by potential mediation of plasma metabolites: A Mendelian randomization study

作者：Shidong Zhao, Xianjing Zheng, Changjiang Yang, Weisong Shen, Zhanlong Shen · 发表于：Medicine · 年份：2025 · DOI：10.1097/md.0000000000042791 · 被引用次数：4 · 研究领域：Gut microbiota and health、Cancer-related molecular mechanisms research、Mycobacterium research and diagnosis

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with a multifactorial etiology, including genetic, immunological, and environmental factors, as well as alterations in the gut microbiome and plasma metabolites. The interplay between these factors is complex and not fully elucidated, particularly regarding the potential mediation of metabolites in the relationship between gut microbiota and UC. We performed a Mendelian randomization (MR) study to investigate the causal associations between gut microbiota, plasma metabolites, and UC. The study utilized a two-sample MR approach to discern causal relationships among these factors. Genetic variants from genome-wide association studies served as instrumental variables in the MR analyses, conducted using the "TwoSampleMR" package in R software. We adhered to the fundamental assumptions of MR analyses, ensuring the validity of our causal inferences. Additionally, we incorporated a mediation analysis to assess the potential mediating role of plasma metabolites in the relationship between gut microbiota and UC. Our current study found the substantial relationship between certain gut microbial taxa and the development of UC. Indeed, we have identified 6 microbial taxa, including Genus Dorea, Phylum Proteobacteria, Species Streptococcus parasanguinis, Species Ruminococcus obeum, Species Roseburia intestinalis, and Order Lactobacillales, which were found to be causally related to UC. Seventy-three metabolites and metabolite...