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A Double Humanized BLT-mice Model Featuring a Stable Human-Like Gut Microbiome and Human Immune System
Published on: August 30, 2019
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Gut microbiome for predicting immune checkpoint blockade-associated adverse events
Muni Hu1, Xiaolin Lin2, Tiantian Sun1
1State Key Laboratory of Systems Medicine for Cancer, NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai Cancer Institute, Shanghai, 200001, China.
Genome Medicine
|January 19, 2024
Summary
This study identifies gut microbes that predict immune-related adverse events (irAEs) from immune checkpoint inhibitors (ICIs). Menaquinone, a microbial metabolite, was found to be higher in patients without irAEs, suggesting its therapeutic potential.
Area of Science:
- Immunology
- Microbiome Research
- Metabolomics
Background:
- Immune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs).
- The gut microbiome's role in irAEs is known, but associations vary across studies.
- Predicting irAEs remains a challenge.
Purpose of the Study:
- To develop a microbiome-based classifier for predicting irAEs.
- To identify microbial and metabolic factors associated with irAEs.
- To explore mechanisms underlying irAE development.
Main Methods:
- Comprehensive analysis of published and in-house microbiome data (16S rRNA and shotgun metagenomics).
- Machine learning (Random Forest) model construction for irAE prediction.
- Integration of transcriptome and metagenome profiling for mechanistic insights.
Main Results:
- Identified specific microbial species differentiating irAE and non-irAE patients.
- Developed a Random Forest classifier with high discriminatory power (AUC=0.88).
- Found increased menaquinone biosynthesis and higher serum menaquinone levels in non-irAE patients.
Conclusions:
- Microbial biomarkers show potential for predicting irAE onset.
- Menaquinone, a microbiome-derived metabolite, may be a therapeutic target for modulating irAEs.
- This research offers insights into microbiome-host interactions in ICI therapy.
Keywords:
Gut microbiomeImmune checkpoint inhibitorsImmune-related adverse eventsProgrammed death 1 (PD-1)/programmed death ligand 1 (PD-L1)More Related Videos
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