结直肠癌中免疫-肠道微生物群相互作用的新见解：孟德尔随机研究。

IF 3.1 2区医学 Q3 IMMUNOLOGY

Infectious Agents and Cancer Pub Date : 2025-04-18 DOI:10.1186/s13027-025-00653-3

Zenghui Liu, Xiaohui Zhou, Lu Kuang, Qijun Chen, Jiaxing Zhao, Huayu Yin, Zeyu Zhou, Xuehui Liu, Dabin Liu, Shaoguo Wu, Limei Wu

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引用次数: 0

摘要

背景：免疫细胞与结直肠癌（CRC）发展的关系已被广泛研究；然而，肠道菌群在这种关系中的中介作用仍然知之甚少。方法：我们利用全基因组关联研究（GWAS）的汇总数据分析了731种免疫细胞表型、473种肠道微生物群和crc相关数据。采用两步中介分析来鉴定介导的肠道微生物群。主要分析方法为方差反加权（IVW），辅以MR-Egger、简单模型、加权中位数和加权模型分析。通过系统敏感性分析，保证了结果的稳健性。结果：我们的分析确定了13种与结直肠癌显著相关的免疫细胞表型，包括10种保护因子和3种危险因子。此外，13种肠道菌群与结直肠癌有显著相关性，包括8种保护因子和5种危险因子。介导分析显示，4种肠道菌群（1目、1科、1属、1未分类）介导了免疫细胞与结直肠癌的关系。例如，未分类CAG - 977介导FSC-A对NK和NKT %淋巴细胞对结直肠癌风险的影响，介导比例分别为11%和12.3%。值得注意的是，EM CD8br %CD8br对CRC的保护作用中有22.3%是通过Francisellales介导的。结论：本研究为免疫细胞、肠道菌群和结直肠癌之间的潜在因果关系提供了证据，突出了特定肠道菌群的介导作用。这些发现为CRC的发病机制提供了新的见解，并可能为未来的治疗策略提供信息。

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Novel insights into immune-gut microbiota interactions in colorectal cancer: a Mendelian randomization study.

Background: The relationship between immune cells and colorectal cancer (CRC) development has been extensively studied; however, the mediating role of gut microbiota in this relationship remains poorly understood.

Methods: We utilized summary data from genome-wide association studies (GWAS) to analyze 731 immune cell phenotypes, 473 gut microbiota, and CRC-related data. A two-step mediation analysis was employed to identify mediating gut microbiota. The primary analysis method was inverse variance weighting (IVW), supplemented by MR-Egger, simple mode, weighted median, and weighted mode analyses. Robustness of the results was ensured through systematic sensitivity analyses.

Results: Our analysis identified 13 immune cell phenotypes significantly associated with CRC, including 10 protective factors and 3 risk factors. Additionally, 13 gut microbiota showed significant associations with CRC, comprising 8 protective factors and 5 risk factors. Mediation analysis revealed that 4-gut microbiota (1 order, 1 family, 1 genus, and 1 unclassified) mediated the relationship between immune cells and CRC. For instance, unclassified CAG - 977 mediated the effects of FSC-A on NK and NKT %lymphocyte on CRC risk, with mediation proportions of 11% and 12.3%, respectively. Notably, 22.3% of the protective effect of EM CD8br %CD8br on CRC was mediated through order Francisellales.

Conclusion: This study provides evidence for a potential causal relationship between immune cells, gut microbiota, and CRC, highlighting the mediating role of specific gut microbiota. These findings offer new insights into the pathogenesis of CRC and may inform future therapeutic strategies.

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来源期刊

Infectious Agents and Cancer ONCOLOGY-IMMUNOLOGY

CiteScore

5.80

自引率

2.70%

发文量

期刊介绍： Infectious Agents and Cancer is an open access, peer-reviewed online journal that encompasses all aspects of basic, clinical, epidemiological and translational research providing an insight into the association between chronic infections and cancer. The journal welcomes submissions in the pathogen-related cancer areas and other related topics, in particular: • HPV and anogenital cancers, as well as head and neck cancers; • EBV and Burkitt lymphoma; • HCV/HBV and hepatocellular carcinoma as well as lymphoproliferative diseases; • HHV8 and Kaposi sarcoma; • HTLV and leukemia; • Cancers in Low- and Middle-income countries. The link between infection and cancer has become well established over the past 50 years, and infection-associated cancer contribute up to 16% of cancers in developed countries and 33% in less developed countries. Preventive vaccines have been developed for only two cancer-causing viruses, highlighting both the opportunity to prevent infection-associated cancers by vaccination and the gaps that remain before vaccines can be developed for other cancer-causing agents. These gaps are due to incomplete understanding of the basic biology, natural history, epidemiology of many of the pathogens that cause cancer, the mechanisms they exploit to cause cancer, and how to interrupt progression to cancer in human populations. Early diagnosis or identification of lesions at high risk of progression represent the current most critical research area of the field supported by recent advances in genomics and proteomics technologies.