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Volume 41 Issue 4
August 2026

    . doi: 10.1016/j.virs.2026.08.010
    Citation: Yi Zhou, Qing Guo, Xingyue Zhao, Wei Zhang, Han Zhang, Shiyin Huang, Zihan He, Youhua Xie, Wen Zhang, Jinhua Gu, Shaokun Pan, Wang Li. Blood and gut virome remodeling in gastric cancer: Anellovirus expansion and novel virus discovery .VIROLOGICA SINICA, 2026, 41(4) : 791-805.  http://dx.doi.org/10.1016/j.virs.2026.08.010
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    胃癌中的血液与肠道病毒组重塑：指环病毒扩增与新病毒发现

    • a 南京医科大学附属泰州人民医院;

    • b 复旦大学上海市重大传染病和生物安全研究院;

    • c 安徽医科大学临床医学院;

    • d 江苏大学医学院检验医学系

    • 胃癌（GC）是全球高发的恶性肿瘤，其临床管理的主要挑战在于显著的肿瘤异质性以及缺乏有效的早期诊断工具。尽管肠道微生物组在胃癌发生中的作用已相对明确，但作为肿瘤微环境重要组成部分的病毒组，其群落结构、生态功能及其与胃癌进展的关联仍知之甚少，这在很大程度上限制了对胃癌病因学的全面认识。本研究旨在系统描绘胃癌患者与健康对照者外周血及粪便样本的病毒组图谱，比较两组间群落结构差异，并识别与胃癌发生及转移密切相关的潜在病毒标志物。我们对100例胃癌患者（其中非转移性45例、转移性55例）及50例健康对照者的外周血和粪便样本构建混合文库，进行病毒宏基因组测序，并开展生物信息学分析，包括分类注释、多样性评估、差异丰度检验（LEfSe）及共现网络构建。结果显示，在血液中，胃癌患者的病毒组由对照中以噬菌体为主的谱型显著转变为以指环病毒科（Anelloviridae）绝对优势（>80%）的谱型，同时α多样性显著降低；而肠道病毒组则呈现α多样性升高及多种噬菌体共存的格局。LEfSe分析鉴定出血液中的指环病毒β属（betatorquevirus）为区分胃癌的潜在关键分类单元。网络分析显示，指环病毒科与多个噬菌体科呈负相关，提示可能存在生态位竞争。此外，我们在胃癌患者血液中发现了67种暂定的新型指环病毒（anellovirus）和1种新型gemykibivirus。综上，本研究表明胃癌与血液和肠道中区室特异性的病毒组重塑相关，血液中指环病毒的扩增有望成为非侵入性生物标志物。该研究为深入理解病毒组在胃癌中的作用提供了基础数据资源。

    Blood and gut virome remodeling in gastric cancer: Anellovirus expansion and novel virus discovery

    • a. The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou 225300, China;

    • b. Shanghai Institute of Infectious Diseases and Biosecurity, Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Department of Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 20032, China;

    • c. Clinical College of Anhui Medical University, Hefei 230031, China;

    • d. Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, China

    • Gastric cancer (GC) is a prevalent malignancy worldwide, yet effective early diagnostic tools remain lacking, and the role of the virome, a key component of the tumor microenvironment, in GC progression is largely unknown. This study aimed to characterize the virome landscapes in peripheral blood and feces of GC patients versus healthy controls, and to identify viral signatures associated with GC onset and metastasis. We performed viral metagenomic sequencing on pooled libraries from 100 GC patients (45 non-metastatic, 55 metastatic) and 50 healthy controls, followed by taxonomic annotation, diversity assessment, LEfSe differential abundance testing, and co-occurrence network analysis. In blood, the GC virome shifted from a bacteriophage-dominated profile in controls to one overwhelmingly dominated by Anelloviridae (> 80%), with significantly decreased alpha diversity. In contrast, the gut virome of GC patients showed increased alpha diversity and coexistence of diverse bacteriophages. LEfSe identified betatorquevirus in blood as a key discriminatory taxon for GC. Network analysis revealed negative correlations between Anelloviridae and multiple bacteriophage families, suggesting niche competition. We also discovered 67 provisional novel anellovirus species and one novel gemykibivirus in GC patient blood. Collectively, our findings indicate that GC is associated with compartment-specific virome remodeling in blood and gut, and that expansion of blood anelloviruses holds promise as a non-invasive biomarker. This study provides a foundational resource for understanding the virome's role in GC.
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      Blood and gut virome remodeling in gastric cancer: Anellovirus expansion and novel virus discovery

        Corresponding author: Jinhua Gu, tzsrmyy@126.com
        Corresponding author: Shaokun Pan, skpan@fudan.edu.cn
        Corresponding author: Wang Li, liwang20091221@126.com
      • a. The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou 225300, China;
      • b. Shanghai Institute of Infectious Diseases and Biosecurity, Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Department of Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 20032, China;
      • c. Clinical College of Anhui Medical University, Hefei 230031, China;
      • d. Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, China
      • Received Date: 13 April 2026
      • Accepted Date: 10 August 2026

      Abstract: Gastric cancer (GC) is a prevalent malignancy worldwide, yet effective early diagnostic tools remain lacking, and the role of the virome, a key component of the tumor microenvironment, in GC progression is largely unknown. This study aimed to characterize the virome landscapes in peripheral blood and feces of GC patients versus healthy controls, and to identify viral signatures associated with GC onset and metastasis. We performed viral metagenomic sequencing on pooled libraries from 100 GC patients (45 non-metastatic, 55 metastatic) and 50 healthy controls, followed by taxonomic annotation, diversity assessment, LEfSe differential abundance testing, and co-occurrence network analysis. In blood, the GC virome shifted from a bacteriophage-dominated profile in controls to one overwhelmingly dominated by Anelloviridae (> 80%), with significantly decreased alpha diversity. In contrast, the gut virome of GC patients showed increased alpha diversity and coexistence of diverse bacteriophages. LEfSe identified betatorquevirus in blood as a key discriminatory taxon for GC. Network analysis revealed negative correlations between Anelloviridae and multiple bacteriophage families, suggesting niche competition. We also discovered 67 provisional novel anellovirus species and one novel gemykibivirus in GC patient blood. Collectively, our findings indicate that GC is associated with compartment-specific virome remodeling in blood and gut, and that expansion of blood anelloviruses holds promise as a non-invasive biomarker. This study provides a foundational resource for understanding the virome's role in GC.

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