Characterization of the landscape of the intratumoral microbiota reveals that Streptococcus anginosus increases the risk of gastric cancer initiation and progression

Abstract As a critical component of the tumour immune microenvironment (TIME), the resident microbiota promotes tumorigenesis across a variety of cancer types. Here, we integrated multiple types of omics data, including microbiome, transcriptome, and metabolome data, to investigate the functional ro...

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Main Authors: Li Yuan, Libin Pan, Yunzhe Wang, Jing Zhao, Luo Fang, Ying Zhou, Ruihong Xia, Yubo Ma, Zhengchen Jiang, Zhiyuan Xu, Can Hu, Yanan Wang, Shengjie Zhang, Bo Zhang, Haiying Ding, Mengxuan Chen, Haibo Cheng, Ajay Goel, Zhao Zhang, Xiangdong Cheng
Format: Article
Language:English
Published: Nature Publishing Group 2024-11-01
Series:Cell Discovery
Online Access:https://doi.org/10.1038/s41421-024-00746-0
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author Li Yuan
Libin Pan
Yunzhe Wang
Jing Zhao
Luo Fang
Ying Zhou
Ruihong Xia
Yubo Ma
Zhengchen Jiang
Zhiyuan Xu
Can Hu
Yanan Wang
Shengjie Zhang
Bo Zhang
Haiying Ding
Mengxuan Chen
Haibo Cheng
Ajay Goel
Zhao Zhang
Xiangdong Cheng
author_facet Li Yuan
Libin Pan
Yunzhe Wang
Jing Zhao
Luo Fang
Ying Zhou
Ruihong Xia
Yubo Ma
Zhengchen Jiang
Zhiyuan Xu
Can Hu
Yanan Wang
Shengjie Zhang
Bo Zhang
Haiying Ding
Mengxuan Chen
Haibo Cheng
Ajay Goel
Zhao Zhang
Xiangdong Cheng
author_sort Li Yuan
collection DOAJ
description Abstract As a critical component of the tumour immune microenvironment (TIME), the resident microbiota promotes tumorigenesis across a variety of cancer types. Here, we integrated multiple types of omics data, including microbiome, transcriptome, and metabolome data, to investigate the functional role of intratumoral bacteria in gastric cancer (GC). The microbiome was used to categorize GC samples into six subtypes, and patients with a high abundance of Streptococcus or Pseudomonas had a markedly worse prognosis. Further assays revealed that Streptococcus anginosus (SA) promoted tumour cell proliferation and metastasis while suppressing the differentiation and infiltration of CD8+ T cells. However, antibiotic treatment significantly suppressed tumorigenesis in SA+ mice in vivo. We further demonstrated that the SA arginine pathway increased the abundance of ornithine, which may be a major contributor to reshaping of the TIME. Our findings demonstrated that SA, a novel risk factor, plays significant roles in the initiation and progression of GC, suggesting that SA might be a promising target for the diagnosis and treatment of GC.
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issn 2056-5968
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series Cell Discovery
spelling doaj-art-45a47d097af4446bbaab48e61681c96f2024-12-01T12:09:23ZengNature Publishing GroupCell Discovery2056-59682024-11-0110111510.1038/s41421-024-00746-0Characterization of the landscape of the intratumoral microbiota reveals that Streptococcus anginosus increases the risk of gastric cancer initiation and progressionLi Yuan0Libin Pan1Yunzhe Wang2Jing Zhao3Luo Fang4Ying Zhou5Ruihong Xia6Yubo Ma7Zhengchen Jiang8Zhiyuan Xu9Can Hu10Yanan Wang11Shengjie Zhang12Bo Zhang13Haiying Ding14Mengxuan Chen15Haibo Cheng16Ajay Goel17Zhao Zhang18Xiangdong Cheng19Department of Integrated Chinese and Western Medicine, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of SciencesDepartment of Pharmacy, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of SciencesMOE Key Laboratory of Metabolism and Molecular Medicine, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan UniversityZhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer, Zhejiang Cancer HospitalDepartment of Pharmacy, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of SciencesDepartment of Pharmacy, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of SciencesZhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer, Zhejiang Cancer HospitalZhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer, Zhejiang Cancer HospitalZhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer, Zhejiang Cancer HospitalDepartment of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of SciencesDepartment of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of SciencesZhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer, Zhejiang Cancer HospitalZhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer, Zhejiang Cancer HospitalDepartment of Integrated Chinese and Western Medicine, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of SciencesDepartment of Pharmacy, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of SciencesShanghai Analytical Applications Center, Shimadzu (China) Co., LTDThe First School of Clinical Medicine, Nanjing University of Chinese MedicineDepartment of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope Comprehensive Cancer CenterMOE Key Laboratory of Metabolism and Molecular Medicine, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan UniversityZhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer HospitalAbstract As a critical component of the tumour immune microenvironment (TIME), the resident microbiota promotes tumorigenesis across a variety of cancer types. Here, we integrated multiple types of omics data, including microbiome, transcriptome, and metabolome data, to investigate the functional role of intratumoral bacteria in gastric cancer (GC). The microbiome was used to categorize GC samples into six subtypes, and patients with a high abundance of Streptococcus or Pseudomonas had a markedly worse prognosis. Further assays revealed that Streptococcus anginosus (SA) promoted tumour cell proliferation and metastasis while suppressing the differentiation and infiltration of CD8+ T cells. However, antibiotic treatment significantly suppressed tumorigenesis in SA+ mice in vivo. We further demonstrated that the SA arginine pathway increased the abundance of ornithine, which may be a major contributor to reshaping of the TIME. Our findings demonstrated that SA, a novel risk factor, plays significant roles in the initiation and progression of GC, suggesting that SA might be a promising target for the diagnosis and treatment of GC.https://doi.org/10.1038/s41421-024-00746-0
spellingShingle Li Yuan
Libin Pan
Yunzhe Wang
Jing Zhao
Luo Fang
Ying Zhou
Ruihong Xia
Yubo Ma
Zhengchen Jiang
Zhiyuan Xu
Can Hu
Yanan Wang
Shengjie Zhang
Bo Zhang
Haiying Ding
Mengxuan Chen
Haibo Cheng
Ajay Goel
Zhao Zhang
Xiangdong Cheng
Characterization of the landscape of the intratumoral microbiota reveals that Streptococcus anginosus increases the risk of gastric cancer initiation and progression
Cell Discovery
title Characterization of the landscape of the intratumoral microbiota reveals that Streptococcus anginosus increases the risk of gastric cancer initiation and progression
title_full Characterization of the landscape of the intratumoral microbiota reveals that Streptococcus anginosus increases the risk of gastric cancer initiation and progression
title_fullStr Characterization of the landscape of the intratumoral microbiota reveals that Streptococcus anginosus increases the risk of gastric cancer initiation and progression
title_full_unstemmed Characterization of the landscape of the intratumoral microbiota reveals that Streptococcus anginosus increases the risk of gastric cancer initiation and progression
title_short Characterization of the landscape of the intratumoral microbiota reveals that Streptococcus anginosus increases the risk of gastric cancer initiation and progression
title_sort characterization of the landscape of the intratumoral microbiota reveals that streptococcus anginosus increases the risk of gastric cancer initiation and progression
url https://doi.org/10.1038/s41421-024-00746-0
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