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Gut microbiome for predicting immune checkpoint blockade-associated adverse events.
Hu, Muni; Lin, Xiaolin; Sun, Tiantian; Shao, Xiaoyan; Huang, Xiaowen; Du, Weiwei; Guo, Mengzhe; Zhu, Xiaoqiang; Zhou, Yilu; Tong, Tianying; Guo, Fangfang; Han, Ting; Wu, Xiuqi; Shi, Yi; Xiao, Xiuying; Zhang, Youwei; Hong, Jie; Chen, Haoyan.
Afiliación
  • Hu M; State 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.
  • Lin X; Department of Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
  • Sun T; State 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.
  • Shao X; Department of Medical Oncology, Xuzhou Central Hospital, Clinical School of Xuzhou Medical University, Xuzhou, 221009, China.
  • Huang X; State 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.
  • Du W; Department of Medical Oncology, Xuzhou Central Hospital, Clinical School of Xuzhou Medical University, Xuzhou, 221009, China.
  • Guo M; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China.
  • Zhu X; State 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.
  • Zhou Y; State 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.
  • Tong T; State 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.
  • Guo F; Department of Gastroenterology, the First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China.
  • Han T; Department of Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
  • Wu X; Department of Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
  • Shi Y; Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, China.
  • Xiao X; Department of Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China. xiaoxiuying2002@163.com.
  • Zhang Y; Department of Medical Oncology, Xuzhou Central Hospital, Clinical School of Xuzhou Medical University, Xuzhou, 221009, China. zhangyw@njmu.edu.cn.
  • Hong J; State 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.
  • Chen H; State 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 Med ; 16(1): 16, 2024 01 19.
Article en En | MEDLINE | ID: mdl-38243343
ABSTRACT

BACKGROUND:

The impact of the gut microbiome on the initiation and intensity of immune-related adverse events (irAEs) prompted by immune checkpoint inhibitors (ICIs) is widely acknowledged. Nevertheless, there is inconsistency in the gut microbial associations with irAEs reported across various studies.

METHODS:

We performed a comprehensive analysis leveraging a dataset that included published microbiome data (n = 317) and in-house generated data from 16S rRNA and shotgun metagenome samples of irAEs (n = 115). We utilized a machine learning-based approach, specifically the Random Forest (RF) algorithm, to construct a microbiome-based classifier capable of distinguishing between non-irAEs and irAEs. Additionally, we conducted a comprehensive analysis, integrating transcriptome and metagenome profiling, to explore potential underlying mechanisms.

RESULTS:

We identified specific microbial species capable of distinguishing between patients experiencing irAEs and non-irAEs. The RF classifier, developed using 14 microbial features, demonstrated robust discriminatory power between non-irAEs and irAEs (AUC = 0.88). Moreover, the predictive score from our classifier exhibited significant discriminative capability for identifying non-irAEs in two independent cohorts. Our functional analysis revealed that the altered microbiome in non-irAEs was characterized by an increased menaquinone biosynthesis, accompanied by elevated expression of rate-limiting enzymes menH and menC. Targeted metabolomics analysis further highlighted a notably higher abundance of menaquinone in the serum of patients who did not develop irAEs compared to the irAEs group.

CONCLUSIONS:

Our study underscores the potential of microbial biomarkers for predicting the onset of irAEs and highlights menaquinone, a metabolite derived from the microbiome community, as a possible selective therapeutic agent for modulating the occurrence of irAEs.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos / Microbioma Gastrointestinal / Antineoplásicos Inmunológicos / Enfermedades del Sistema Inmune / Neoplasias Pulmonares / Neoplasias Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Genome Med Año: 2024 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos / Microbioma Gastrointestinal / Antineoplásicos Inmunológicos / Enfermedades del Sistema Inmune / Neoplasias Pulmonares / Neoplasias Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Genome Med Año: 2024 Tipo del documento: Article País de afiliación: China