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胃癌患者肠道菌群失调与细胞因子表达异常的关联分析及临床意义

Correlation and Clinical Significance of Intestinal Microbiota Dysbiosis and Abnormal Cytokine Expression in Patients with Gastric Cancer

  • 摘要:
    目的 探讨胃癌患者肠道菌群组成的改变与细胞因子表达异常的相关性。
    方法 收集81例胃腺癌患者(胃癌组)和85例健康体检者(健康对照组)的粪便与外周血样本,分别采用16S rRNA基因测序技术对粪便细菌DNA进行测序分析,采用AimPlex流式高通量多因子检测技术对外周血中17种细胞因子(IL-1β、IL-2、IL-4、IL-6、IL-8、IL-10、IL-12p70、IL-15、IL-17A、TNF-α、TNF-β、GM-CSF、G-CSF、IFN-γ、IP-10、MCP-1、VEGF-A)的浓度进行检测。
    结果 胃癌组中,毛螺菌科部分菌属(LachnospiraRoseburia等)、Faecalibacterium等11种产丁酸菌丰度显著减少,Escherichia-ShigellaStreptococcusVeillonellaParabacteroides等9种细菌的丰度显著增加。相关性分析显示,丰度减少的产丁酸菌与胃癌组中高表达的促血管生成及免疫抑制细胞因子(包括IP-10、IL-10、MCP-1、IL-8、IL-6和VEGF-A)呈显著负相关,而与低表达的抗肿瘤免疫相关因子(包括IL-2、IL-17A、IL-1β、TNF-β和GM-CSF)呈显著正相关。相反,丰度升高的菌群与上述细胞因子呈相反的相关性模式。
    结论 胃癌患者肠道菌群失调与细胞因子表达异常存在密切相关性。基于这一关联,粪菌移植修复肠道菌群进而调节细胞因子的策略,有望成为胃癌辅助治疗的潜在研究方向。

     

    Abstract:
    Objective To explore the correlation between alterations in intestinal microbiota composition and abnormal cytokine expression in patients with gastric cancer.
    Methods Fecal and peripheral blood samples were collected from 81 patients with gastric cancer (gastric cancer group) and 85 healthy subjects (healthy control group). Fecal bacterial DNA was sequenced through 16S rRNA gene amplicon sequencing, and the serum levels of 17 cytokines were measured with the AimPlex multiplex assay technology: interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-15, IL-17A, tumor necrosis factor (TNF)-α, TNF-β, granulocyte- macrophage colony-stimulating factor (GM-CSF), granulocyte-colony-stimulating factor (G-CSF), interferon-γ, interferon gamma-induced protein 10, macrophage chemotactic protein 1 (MCP-1), and vascular endothelial growth factor A (VEGF-A).
    Results In the gastric cancer group, the abundances of 11 butyrate-producing bacteria, including certain genera of the Lachnospiraceae family (such as Lachnospira and Roseburia) and Faecalibacterium, considerably decreased. By contrast, the abundances of nine bacterial taxa, including Escherichia–Shigella, Streptococcus, Veillonella, and Parabacteroides, significantly increased. Correlation analysis showed that the decrease in the abundance of butyrate-producing bacteria were significantly negatively correlated with the high expression levels of pro-angiogenic and immunosuppressive cytokines in the gastric cancer group, including IP-10, IL-10, MCP-1, IL-8, IL-6, and VEGF-A. However, the decrease was significantly positively correlated with the downregulation of antitumor immune-related cytokines, including IL-2, IL-17A, IL-1β, TNF-β, and GM-CSF. Conversely, the enriched bacterial taxa exhibited opposite correlation patterns with these cytokines.
    Conclusion A close correlation is observed between intestinal microbiota dysbiosis and abnormal cytokine expression in patients with gastric cancer. The findings suggest that restoring the intestinal microbiota through fecal microbiota transplantation is a promising strategy for regulating cytokines and is a potential research direction for the adjuvant therapy of gastric cancer.

     

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