肠道微生物群因果影响药物诱导的肝损伤通过血代谢物:孟德尔的随机化研究
Haoshuang Fu1, Shuang Zhao2, Shuying Song1
1Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Frontiers in microbiology
|August 2, 2024
概括
肠道微生物群和血代谢物因果影响药物诱导性肝损伤 (DILI). 特定的肠道细菌如Blautia和Oscillospira通过介导代谢物对DILI产生影响,为风险分层提供潜在的生物标志物.
科学领域:
- 微生物学 微生物学
- 代谢学 代谢学 代谢学
- 肝病学 肝病学是一种肝病学.
背景情况:
- 药物诱导性肝损伤 (DILI) 是一个重要的临床问题.
- 肠道微生物群和血代谢组都与DILI的发病有关.
- 了解它们的相互作用对于DILI管理至关重要.
研究的目的:
- 调查肠道微生物群,血代谢物和DILI之间的因果关系.
- 为了确定与DILI风险相关的特定微生物种群和代谢物.
- 探索代谢物在肠道微生物群中的调解作用-DILI轴.
主要方法:
- 利用了大规模的全基因组关联研究总结数据,用于肠道微生物群 (n=18,340),血代谢组 (n=8,299) 和 DILI (n=366,838).
- 采用两个样本的门德尔随机化来评估因果关系.
- 进行了双阶段的门德尔随机化和调解分析,以确定调解代谢物.
主要成果:
- 五种肠道微生物种群,包括 * Oscillospira * 和 * Blautia *,显示与 DILI 的因果关系.
- 发现53种血代谢物与DILI有因果关系.
- 四种类型通过五种介导代谢物,如N6-carbamoylthreonyladenosine和乙卡尼丁,影响DILI.
结论:
- 肠道微生物群通过血代谢物的改变对DILI产生影响.
- 已识别的微生物种群和介导代谢物可以作为DILI风险分层的潜在生物标志物.
- 这些发现提供了对DILI背后的机制的见解.
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