Association Between Gut Microbiota and Hirschsprung Disease: a Bidirectional Two-sample Mendelian Randomization Study

Overview

Journal Front Microbiol

Specialty Microbiology

Date 2024 Mar 22

PMID 38516012

Authors

Wei Liu

Hanlei Yan

Wanying Jia

Jingjing Huang

Zihao Fu

Wenyao Xu

Hui Yu

Weili Yang

Weikang Pan

Baijun Zheng

Yong Liu

Xinlin Chen

Ya Gao

Donghao Tian

Affiliations

Soon will be listed here.

Abstract

Background: Several studies have pointed to the critical role of gut microbiota (GM) and their metabolites in Hirschsprung disease (HSCR) pathogenesis. However, the detailed causal relationship between GM and HSCR remains unknown.

Methods: In this study, we used two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between GM and HSCR, based on the MiBioGen Consortium's genome-wide association study (GWAS) and the GWAS Catalog's HSCR data. Reverse MR analysis was performed subsequently, and the sensitivity analysis, Cochran's Q-test, MR pleiotropy residual sum, outlier (MR-PRESSO), and the MR-Egger intercept were used to analyze heterogeneity or horizontal pleiotropy. 16S rDNA sequencing and targeted mass spectrometry were developed for initial validation.

Results: In the forward MR analysis, inverse-variance weighted (IVW) estimates suggested that Eggerthella (OR: 2.66, 95%CI: 1.23-5.74, = 0.01) was a risk factor for HSCR, while Peptococcus (OR: 0.37, 95%CI: 0.18-0.73, = 0.004), Ruminococcus2 (OR: 0.32, 95%CI: 0.11-0.91, = 0.03), Clostridiaceae1 (OR: 0.22, 95%CI: 0.06-0.78, = 0.02), Mollicutes RF9 (OR: 0.27, 95%CI: 0.09-0.8, = 0.02), Ruminococcaceae (OR: 0.16, 95%CI: 0.04-0.66, = 0.01), and Paraprevotella (OR: 0.45, 95%CI: 0.21-0.98, = 0.04) were protective factors for HSCR, which had no heterogeneity or horizontal pleiotropy. However, reverse MR analysis showed that HSCR (OR: 1.02, 95%CI: 1-1.03, = 0.049) is the risk factor for Eggerthella. Furthermore, some of the above microbiota and short-chain fatty acids (SCFAs) were altered in HSCR, showing a correlation.

Conclusion: Our analysis established the relationship between specific GM and HSCR, identifying specific bacteria as protective or risk factors. Significant microbiota and SCFAs were altered in HSCR, underlining the importance of further study and providing new insights into the pathogenesis and treatment.

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