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Gut microbiota causally affects drug-induced liver injury via plasma metabolites: a Mendelian randomization study

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
PubMed
Abstract

Insights

Gut microbiota and plasma metabolites causally influence drug-induced liver injury (DILI). Specific gut bacteria like Blautia and Oscillospira impact DILI through mediating metabolites, offering potential biomarkers for risk stratification.

Area of Science:

  • Microbiology
  • Metabolomics
  • Hepatology

Background:

  • Drug-induced liver injury (DILI) is a significant clinical concern.
  • The gut microbiota and plasma metabolome are implicated in DILI pathogenesis.
  • Understanding their interplay is crucial for DILI management.

Purpose of the Study:

  • To investigate the causal relationships between gut microbiota, plasma metabolites, and DILI.
  • To identify specific microbial taxa and metabolites associated with DILI risk.
  • To explore the mediating role of metabolites in the gut microbiota-DILI axis.

Main Methods:

  • Utilized large-scale genome-wide association study summary data for gut microbiota (n=18,340), plasma metabolome (n=8,299), and DILI (n=366,838).
  • Employed two-sample Mendelian randomization to assess causal associations.
  • Conducted two-step Mendelian randomization and mediation analysis to identify mediating metabolites.

Main Results:

  • Five gut microbial taxa, including *Oscillospira* and *Blautia*, showed causal associations with DILI.
  • Fifty-three plasma metabolites were found to be causally linked to DILI.
  • Four taxa influenced DILI via five mediating metabolites, such as N6-carbamoylthreonyladenosine and acetylcarnitine.

Conclusions:

  • The gut microbiota exerts influence on DILI through alterations in plasma metabolites.
  • Identified microbial taxa and mediating metabolites may serve as potential biomarkers for DILI risk stratification.
  • These findings provide insights into the mechanisms underlying DILI.
Keywords:
Mendelian randomizationdrug-induced liver diseasegut microbiotaliver diseaseplasma metabolometoxic liver disease

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