1969-2019年血液微生物组研究纵览 | 血液微生物组
大量研究已将临床疾病与人类微生物群落组成的变化联系在一起，使得利用微生物作为诊断人类重大疾病成为可能。越来越多的证据表明，血液微生物特征可作为疾病相关性分子标志物。虽然血液中细菌DNA的浓度通常非常低，但日益成熟的分析技术（qPCR和NGS）证实健康人类的血液中存在“无害的”细菌类群（Paisse et al.，2016）。微生物组对非感染性疾病和各种癌症的发病机制和发展至关重要。微生物生态失调促进癌变，如结肠直肠癌、肝癌和肺癌等（Dejea et al.，2017）。从人血浆中分离出的循环微生物DNA（cmDNA）可作为一种非侵入性生物标志物，在肿瘤的早期诊断中起着越来越重要的作用（血液循环微生物DNA可作肿瘤标志物？）。
cmDNA可作为肿瘤标志物，对于人体其他疾病是否与血液微生物存在联系？细菌可以从健康人体的外周血中培养出来，微生物基因组DNA在血液中循环，循环微生物的改变可以作为很有价值的疾病生物标志物（Damgaard et al.，2017）。例如，在重症急性胰腺炎患者中，通过16S测序分析了血液微生物发现患者微生物多样性比健康人群少，并且在与健康对照组相比病例组的拟杆菌（Bacteroides）和梭状芽孢杆菌（Clostridium Prazmowski）丰度增加，放线菌（Actinomycete）和黄杆菌（Flavobacterium Bergey）减少(Li et al.，2018)。通过检测到这些优势菌群的强烈变化暗示了胰腺炎患者血液微生物群失调。除此之外，其他各项研究证明血液微生物群的改变与炎症性肠炎、心血管和糖尿病等发病率的增加有关，表1针对近些年来对血液微生物研究进行汇总：“1969-2019”年血液微生物组研究纵览。研究人员通过不同方法描述多种患者和健康人群的血液微生物群（如糖尿病、脓毒症、肝硬化、急性胰腺炎、精神分裂症、双相情感障碍症和哮喘患者等），供大家全景了解血液微生物组研究的方法和进展，更好地站在前人的肩膀上设计自己的血液微生物组课题。
以往对血液微生物的研究运用过很多种方法，但仍有很多局限性，如“血液循环微生物DNA可作肿瘤标志物？”中所述，特别是在污染菌干扰方面，“1969-2019”年血液微生物组研究纵览中的各文献中都提出污染菌去除及优化的问题，到2019-2020年Eisenhofer R和Deborah Nejman等人分别细化污染菌去除流程（Eisenhofer R.,2019）和优化低微生物生物量样本检测技术（5R 16S测序）（Deborah Nejman.，2020），污染菌去除流程详情可见“做肿瘤微生物检测，这些实验设计你都知道吗？”。5R 16S测序技术适合血液微生物的检测，根据我们近百个血液微生物组项目结果来看，对于低微生物生物量样本的检测的灵敏度和特异性更高，相比常规16S测序检出率更高。随着血液微生物的研究不断深入，会有更多的血液微生物被列为重要的检测项目，在疾病中的诊断价值中都具有重要的价值。
表1 1969-2019年血液微生物研究纵览
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