Causality between Gut Microbiota and Inflammatory Bowel Disease: A Bidirectional Mendelian Randomization Study

Abstract

Abstract The exact relationship between inflammatory bowel disease (IBD) and gut microbiota (GM) is still unclear. This study aimed to explore the cause-and-effect relationship between IBD and GM by Mendelian randomization (MR) analysis. The IBD data used in this study were obtained from Genome-Wide Association Studies (GWAS). The GM data were from the Dutch Microbiome Project and included 207 taxa and 205 microbiota-associated pathways. Multivariate Mendelian randomization (MVMR) analysis was performed to investigate the relationship between GM and IBD. The results demonstrated that susceptibility to developing IBD is negatively correlated with class Clostridia (OR = 0.80, P = 0.003), family Sutterellacea (OR = 0.87, P = 0.014), genus Coprobacter (OR = 0.90, P = 0.009), order Clostridiales (OR = 0.80, P = 0.003), phylum Firmicutes (OR = 0.82, P = 0.002) and Coprobacter fastidiosus (OR = 0.90, P = 0.009). Conversely, the risk of developing IBD is positively correlated with the phosphopantothenate biosynthesis I pathway (OR = 1.17, P = 0.006), Bacteroides caccae (OR = 1.14, P = 0.021) and Bacteroides uniformis (OR = 1.26, P = 0.003). Reverse causality was found between the phosphopantothenate biosynthesis I pathway and IBD (OR = 1.03, P = 0.04), but not for the remaining specific GM taxa. In conclusion, our study demonstrated a causal relationship between specific GM features and IBD.