Pulse Brain · Growing Health Evidence Index
Tier 1 — Meta-analysis / systematic reviewPeer-reviewed

Oxidative stress gene expression, DNA methylation, and gut microbiota interaction trigger Crohn’s disease: a multi-omics Mendelian randomization study

Shu Xu, Xiaozhi Li, Shenghong Zhang, Cancan Qi, Zhenhua Zhang, Ruiqi Ma, Liyuan Xiang, Lianmin Chen, Yijun Zhu, Ce Tang, Arno R. Bourgonje, Miaoxin Li, Yao He, Zhirong Zeng, Shixian Hu, Rui Feng, Minhu Chen

BMC Medicine · 2023

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Summary

This multi-omics Mendelian randomization study integrates transcriptomics, epigenetics, and microbiota data to identify putative causal relationships between oxidative stress gene expression and Crohn's disease. Five blood genes (BAD, SHC1, STAT3, MUC1, GPX3) were prioritised as candidate causal factors, with evidence suggesting interactions between host oxidative stress gene regulation and gut microbiota composition. The findings support oxidative stress as a potential aetiological trigger rather than merely a consequence of intestinal inflammation.

Regional applicability

This study was conducted in China using primarily Chinese population data and validation. Whilst the underlying biological mechanisms of oxidative stress and microbiota-host interactions are likely conserved, the generalisability to United Kingdom populations depends on whether the identified genetic variants and their effect sizes are consistent across European ancestry groups, which would require replication studies in UK cohorts.

Key measures

Differentially expressed oxidative stress genes, expression quantitative trait loci (eQTLs), DNA methylation QTLs (mQTLs), fecal microbial QTLs (mbQTLs), genome-wide association study summary statistics for Crohn's disease risk

Outcomes reported

The study identified five blood-derived candidate causal genes (BAD, SHC1, STAT3, MUC1, GPX3) and putative intestinal genes associated with Crohn's disease risk through integration of genome-wide association, gene expression, DNA methylation, and microbial quantitative trait loci data. Results were validated in an independent multi-omics cohort from a Chinese hospital.

Theme
Nutrition & health
Subject
Gut microbiome & human health
Study type
Meta-analysis
Study design
Mendelian randomization study with meta-analysis and independent validation cohort
Source type
Peer-reviewed study
Status
Published
Geography
China
System type
Human clinical
DOI
10.1186/s12916-023-02878-8
Catalogue ID
SNmp6e7b2a-jsn4ep

Topic tags

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