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细菌外囊泡在疾病发生发展中的作用机制及应用前景

罗晓霞 覃思华 王晖迪 周宏伟 何彦

罗晓霞, 覃思华, 王晖迪, 周宏伟, 何彦. 细菌外囊泡在疾病发生发展中的作用机制及应用前景[J]. 协和医学杂志, 2023, 14(5): 915-924. doi: 10.12290/xhyxzz.2023-0260
引用本文: 罗晓霞, 覃思华, 王晖迪, 周宏伟, 何彦. 细菌外囊泡在疾病发生发展中的作用机制及应用前景[J]. 协和医学杂志, 2023, 14(5): 915-924. doi: 10.12290/xhyxzz.2023-0260
LUO Xiaoxia, QIN Sihua, WANG Huidi, ZHOU Hongwei, HE Yan. Mechanism of Bacterial Extracellular Vesicles in Disease Development and Prospects for Application[J]. Medical Journal of Peking Union Medical College Hospital, 2023, 14(5): 915-924. doi: 10.12290/xhyxzz.2023-0260
Citation: LUO Xiaoxia, QIN Sihua, WANG Huidi, ZHOU Hongwei, HE Yan. Mechanism of Bacterial Extracellular Vesicles in Disease Development and Prospects for Application[J]. Medical Journal of Peking Union Medical College Hospital, 2023, 14(5): 915-924. doi: 10.12290/xhyxzz.2023-0260

细菌外囊泡在疾病发生发展中的作用机制及应用前景

doi: 10.12290/xhyxzz.2023-0260
基金项目: 

国家自然科学基金 82272391

国家自然科学基金 82022044

详细信息
    通讯作者:

    何彦, E-mail: bioyanhe@gmail.com

    罗晓霞、覃思华对本文同等贡献

    罗晓霞、覃思华对本文同等贡献

  • 中图分类号: R446.5;R456;R378

Mechanism of Bacterial Extracellular Vesicles in Disease Development and Prospects for Application

Funds: 

National Natural Science Foundation of China 82272391

National Natural Science Foundation of China 82022044

More Information
  • 摘要: 细菌外囊泡(bacterial extracellular vesicles,BEVs)是细菌衍生的细胞外囊泡。作为细菌间或细菌-宿主间相互作用的关键新媒介,BEVs是一把“双刃剑”:一方面在宿主多种病理过程,包括肠道炎性疾病、中枢神经系统相关疾病、肝脏疾病、代谢性疾病、自身免疫性疾病及肿瘤中发挥“致病”作用;另一方面作为潜在生物标志物、疫苗、抗肿瘤制剂等发挥“治病”作用,为疾病的诊治打开了新思路。但关于BEVs的研究目前尚处于起步阶段,在囊泡分离技术、疾病诊断特异性、囊泡储运优化等方面仍面临挑战,未来需设计严谨的临床研究以证实其诊断和治疗价值。
    作者贡献:罗晓霞、覃思华负责文献检索及论文撰写;王晖迪负责论文构思及修订;周宏伟、何彦负责选题设计及论文审校。
    利益冲突:所有作者均声明不存在利益冲突
  • 图  1  细菌外囊泡形成过程示意图

    表  1  BEVs作为潜在生物标志物的最新研究

    第一作者
    (发表时间)
    BEVs
    来源
    疾病 研究对象
    (实验组/对照组)
    研究方法 生物标志物 诊断模型 标志物
    类型
    Dey[43] (2019年) 血清 葡萄球菌菌血症 21例幸存者/23例因菌血症死亡者 对感染金黄色葡萄球菌菌血症幸存者和死亡者血清中的BEVs进行分离 BEVs含量 301相对荧光单位:特异度90%/灵敏度78% 预警标志物
    Wei[44] (2019年) 粪便 AD 9例AD患者/9名健康者 对来自AD患者和健康者的BEVs进行差异代谢物分析 4-半醛/PGE2/20-羟基-二十碳四烯酸/菌素/L -岩藻吡喃糖/吲哚-3-乙酸/4-甲基伞形酮/胆碱/咪唑-4-醋酸/ L-天冬氨酸/富马酸/十三酸 4-半醛/PGE2/20-羟基-二十碳四烯酸/菌素/L-岩藻吡喃糖/吲哚-3-乙酸/4-甲基伞形酮/胆碱:各自AUC>0.900咪唑-4-醋酸/ L-天冬氨酸/富马酸/十三酸:各自AUC>0.800 预测和诊断标志物
    Yang[45](2020年) 血清 脑肿瘤 152例脑肿瘤患者/198名健康者 对BEVs进行16S rRNA基因测序 微生物组成 - 诊断标志物
    Kim[46](2020年) 血清 卵巢癌 166例卵巢癌患者/76例良性肿瘤患者 对BEVs进行宏基因测序,构建卵巢癌与良性卵巢肿瘤的诊断模型 BEVs宏基因组图谱 年龄+ CA-125 +不动杆菌相对丰度:AUC=0.846 鉴别标志物
    Kim[47](2020年) 粪便 结直肠癌 32例结直肠癌患者/40名健康者 联合BEVs的宏基因组学数据和代谢组学数据构建诊断结直肠癌的模型 两种细菌(Collinsella、Solanum melongena)/两种代谢物(leucine、oxalic acid) 宏基因组学+代谢组学:AUC=1 诊断标志物
    Yang[48](2020年) 血清 特发性皮炎 24例特发性皮炎患者/49名健康者 16S rDNA宏基因组分析 BEVs细菌类群 血清BEVs生物标志物(LDA评分>3):AUC=1 诊断标志物
    Yang[49](2020年) 血清 哮喘、COPD、肺癌 239例哮喘患者、205例COPD患者、324例肺癌患者/88名健康者 16S rDNA宏基因组分析,基于ELISA的抗BEVs抗体滴度分析作为肺部疾病的诊断工具 BEVs细菌类群 哮喘:AUC=0.78; COPD:AUC=0.79; 肺癌:AUC=0.80 BEVs抗体滴度的肺部疾病诊断工具
    Han[50](2021年) 唾液 牙周炎 7例牙龈炎患者、8例牙周炎患者/7名健康者 对健康者、牙龈炎和牙周炎患者唾液小细胞BEVs的DNA表观遗传模式、LPS阳性OMVs群体和特异性牙周病原体来源的OMVs进行分析 具核梭杆菌OMVs 具核梭杆菌OMVs:AUC=0.94 鉴别牙龈炎和牙周炎的标志物
    Yoon[51](2023年) 尿液 结直肠癌 91例结直肠癌患者/116名健康者 对BEVs进行16S rRNA基因测序,分析两组间的差异微生物群 微生物组成 - 诊断标志物
    BEVs: 细菌外囊泡;AUC:受试者工作特征曲线下面积;AD: 阿尔茨海默病;CA-125:糖类抗原-125;LDA: 线性判别分析;COPD: 慢性阻塞性肺疾病;LPS: 脂多糖;OMVs: 外膜囊泡;-:未描述
    下载: 导出CSV

    表  2  益生菌细胞外囊泡在疾病治疗中可能发挥的作用

    第一作者(发表时间) 微生物名称 疾病 研究内容 作用
    Ñahui Palomino[56](2019年) 卷曲乳杆菌BC3(Lactobacillus crispatus) HIV感染 介导病毒-细胞相互作用的包膜蛋白暴露减少,减少HIV-1对宿主细胞的附着 抑制病原菌黏附
    加氏乳杆菌BC12(Lactobacillus gasseri)
    Kim[57](2018年) 植物乳杆菌APsulloc 331261(Lactobacillus plantarum) 特发性皮炎 诱导抗炎细胞因子IL-10的分泌及免疫调节细胞因子IL-1β和GM-CSF的分泌; 诱导单核细胞向巨噬细胞转变及巨噬细胞向M2b状态极化 抗炎作用/免疫调节
    Tong[58](2021年) 鼠李糖乳杆菌GG(Lacticaseibacillus rhamnosus) 结肠炎 抑制结肠组织TLR4-NF-κB-NLRP3轴的激活; 降低TNF-α、IL-1β、IL-2和IL-6水平 抗炎作用/免疫调节
    Hu[59](2021年) 罗伊氏乳杆菌BBC3(Lactobacillus reuteri) 结肠炎 降低TNF-α、IL-1β和IL-6的基因表达,增强IL-10和TGF-β的基因表达; 激活巨噬细胞,抑制Th1和Th17介导的炎症反应 抗炎作用/免疫调节
    Lee[60](2022年) 乳链球菌(Lactococcus lactis) 过敏性哮喘 气道高反应性、嗜酸性粒细胞数量、细胞因子分泌和黏液产生显著降低; 刺激DC产生IL-12,诱导Th2转变Th1,降低Ig4 免疫调节
    Croatti[61](2022年) 乳杆菌(lactobacilli) 阴道感染 支持有益物种的定植及防止大肠杆菌、金黄色葡萄球菌、无乳链球菌和粪肠球菌等条件致病菌的黏附 抑制病原菌
    Choi[62](2022年) 嗜黏蛋白阿克曼氏菌ATCC BA 835(Akkermansia muciniphil) 抑郁 恢复海马中MeCP2、Sirt1及神经营养因子的表达 抗抑郁作用
    枯草芽孢杆菌(Bacillus subtilis)
    Ye[63](2023年) 植物乳杆菌(Lactobacillus plantarum) 肝损伤 降低肝细胞氧化损伤、改善脂质代谢、调节肠道菌群 -
    HIV:人类免疫缺陷病毒;IL: 白细胞介素;GM-CSF:粒细胞巨噬细胞刺激因子;TLR4:Toll样受体4;TNF-α:肿瘤坏死因子α;TGF-β: 转化生长因子β;Th:辅助性T细胞;DC:树突状细胞;MeCP2:甲基CpG结合蛋白2;Sirt1:NAD依赖的脱乙酰化酶;-:不作分类
    下载: 导出CSV
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出版历程
  • 收稿日期:  2023-05-31
  • 录用日期:  2023-06-27
  • 网络出版日期:  2023-07-12
  • 刊出日期:  2023-09-30

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