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Causal Relationship Between Intestinal Flora and Irritable Bowel Syndrome Based on Mendelian Randomization and GWAS Data
Received date: 2024-12-05
Revised date: 2025-03-11
Accepted date: 2025-08-05
Online published: 2025-08-06
Supported by
基于互联网+探讨加味资生汤治疗脾虚型IBS-D伴SIBO的临床研究(GZSY2024023); 2024年国家中医优势专科建设项目-脾胃病科(2024010)
Objective： To analyze the causal relationship between intestinal flora and irritable bowel syndrome （IBS） through the two-sample， bidirectional Mendelian randomization （MR） research method， and to provide genetic evidence support for the causal correlation between the two pathogenic risks.Methods： The genetic data of intestinal flora and IBS were obtained from the GWAS database， respectively， and the information of single nucleotide polymorphisms that were strongly correlated between the two were screened as instrumental variables. Bidirectional MR analyses were performed using inverse variance weighting （IVW）， weighted modeling， MR-Egger regression， simple modeling， and weighted median methods， with IVW as the main analysis method. Subsequently， sensitivity tests were performed to assess the reliability and stability of the MR results.Results： Exploring the causal driving effect of intestinal flora on the pathogenesis of IBS by forward MR， the results showed positive causality between family Ruminococcaceae and IBS， and negative causality with family Oxalobacteraceae， genus RuminococcaceaeUCG013 and IBS， and the leave-one-out method showed stable results， and the sensitivity test showed no heterogeneity and horizontal pleiotropy.Reverse MR verification of the feedback regulation effect of IBS pathological state on the structure of flora， the results showed a positive causal relationship between IBS and family Ruminococcaceae， and a negative causal relationship with family Oxalobacteraceae， genus RuminococcaceaeUCG013. The leave-one-out method showed stable results， and the sensitivity analysis suggested the presence of heterogeneity and horizontal pleiotropy.Conclusion： There was a bi-directional causal link between intestinal flora and IBS， with forward MR finding that increased abundance of family Ruminococcaceae was associated with enhanced risk of IBS， and increased abundance of family Oxalobacteraceae， genus RuminococcaceaeUCG013 was associated with a reduced risk of IBS； and reverse MR finding that as the risk of IBS was enhanced， the abundance of family Ruminococcaceae increased， and the abundance of family Oxalobacteraceae， genus RuminococcaceaeUCG013 decreased.It is suggested that there is a "host-flora" bidirectional interaction loop. This study airs to determine new biological markers for the early prediction and therapeutic targets of IBS in clinic， and to provide experimental data and theoretical basis for the study of intestinal flora to reduce occurrence and improve the prognosis of IBS.
Key words： ; Mendelian randomization； ; Intestinal flora； ; Irritable bowel syndrome； ; Causality
JiaCan LI
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Causal Relationship Between Intestinal Flora and
Irritable Bowel Syndrome Based on Mendelian Randomization and GWAS Data
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