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Med Res Rev:口腔微生物组与前列腺疾病

2021-01-08 王聪 Bio生物世界

前列腺疾病在全世界范围内发病率较高,严重影响男性(尤其是中老年男性)的健康和生活质量。随着人类微生物组计划(HMP)的推进,口腔微生物组与人体健康的关联日益受到重视。

前列腺疾病在全世界范围内发病率较高,严重影响男性(尤其是中老年男性)的健康和生活质量。随着人类微生物组计划(HMP)的推进,口腔微生物组与人体健康的关联日益受到重视。口腔微生物组失调,不仅能诱发牙周疾病,也与多种全身性疾病息息相关,如阿尔茨海默氏病、冠状动脉疾病、关节炎和结肠炎等。

近来研究发现,炎症是影响前列腺生长及下尿路症状进展的重要因素,在前列腺疾病中发挥重要作用,但具体的炎症激活机制尚未明确。牙周病是一种常见的慢性炎症性疾病,与前列腺疾病有着共同的危险因素,这些因素可能影响两者的进展。

研究表明,牙周治疗可以显著改善牙周炎伴前列腺炎症患者的国际前列腺症状评分,这意味着口腔微生物组可能作为炎症性疾病(包括前列腺疾病)治疗的新靶标。口腔微生物组到底与前列腺疾病与何关联呢?

2020年12月30日,武汉大学曾宪涛教授团队、杜克大学/南方科技大学胡海亮教授和开封大学的谢文忠教授在 Med Res Rev(IF=9.3)杂志上合作发表题为:A potential therapeutic strategy for prostatic disease by targeting the oral microbiome 的综述论文。

该综述系统总结了已报道的牙周疾病与前列腺疾病的关联研究,揭示了口腔微生物组和前列腺疾病关联的潜在机制,重点分析与口腔致病菌远处传播、炎症、代谢和免疫失调的有关机制,以及如何将其作为靶标以影响前列腺健康。作者通过展望该研究领域存在的未知和挑战及新兴技术的临床应用,为今后的研究提供了方向。武汉大学方程为该综述第一作者,胡海亮和曾宪涛为共同通信作者。

越来越多的证据表明,细菌感染、炎性刺激和环境因素参与前列腺疾病的进展。基础实验表明,口腔细菌感染可刺激炎症反应,从而影响细胞凋亡,并加速某些全身性疾病。口腔微生物与前列腺健康密切相关,但作用机理有待阐明。本文作者从以下几个方面介绍了口腔微生物组通过直接或间接途径影响前列腺疾病的潜在机制(图1)。

直接途径

口腔致病菌远处传播:研究者在动脉粥样硬化斑块和关节炎患者的滑液中,检测到了口腔致病菌(如牙龈卟啉单胞菌、福塞坦氏菌和伴放线共聚菌);且在牙周炎伴良性前列腺疾病患者的牙菌斑和前列腺液中同时检测到了口腔致病菌(牙龈卟啉单胞菌和福塞坦氏菌)。口腔病原体可能从口腔经血液传播到达前列腺,一旦到达前列腺,可发挥类似在口腔中的致病作用,直接诱发前列腺组织学病变。

间接途径

炎症:牙周疾病会导致促炎细胞因子(如 IL-1β、 IL-6、IL-8、TNF-α 和 INF-γ)表达水平升高,使机体长时间处于慢性弱炎症状态,进而刺激全身性疾病的发生。据报道,牙龈卟啉单胞菌等口腔致病菌在动脉粥样硬化病变部位的检出率更高,并且能加重及维持炎症状态。另有研究表明,上述细胞因子在前列腺疾病的发病机制中也发挥重要作用。因此,口腔病原菌可能会加重及维持前列腺的炎症进程。动物实验表明,细菌感染可诱发前列腺炎症,并且与前列腺增生和异常发育有关,如诱发前列腺上皮内瘤变。

代谢:流行病学表明牙周疾病与机体代谢紊乱有关;同时,代谢综合征与前列腺增生相关,在前列腺疾病的发生发展中亦发挥作用。现有证据表明,细菌感染可诱发前列腺炎,而机体代谢紊乱可自动维持或加剧炎症;慢性炎症可能是代谢综合征与前列腺疾病之间的关联因素。因此,口腔病原体可能通过血液途径转移到前列腺,通过调控机体炎症和代谢改变,诱导前列腺细胞异常增殖和凋亡,促进前列腺疾病的发生。

免疫失调:口腔微生物紊乱可诱发机体免疫功能障碍,免疫失调在牙周疾病和前列腺肿瘤中均发挥作用。这意味着,口腔微生物组可作为治疗靶标,调节肿瘤免疫治疗效果。已有研究表明,肠道微生物组可影响某些肿瘤免疫治疗(如anti‐PD‐L1和CTLA‐4 阻滞剂)的疗效,但目前尚缺乏口腔微生物组与肿瘤免疫治疗的直接证据。本文作者也指出,今后应开展相关人体或动物研究,探究口腔微生物组与前列腺癌免疫治疗反应之间的相互作用及其机制。

图1:口腔菌群影响前列腺疾病的作用途径

临床应用

目前,常采用PCR和二代测序(NGS)技术定量检测口腔、外周循环和泌尿系统(包括组织,尿液和前列腺液)的口腔微生物;或采用ELISA(酶联免疫吸附试验)检测血液样本中的口腔微生物特定的抗原或抗体。此外,多功能纳米材料,如免疫磁珠,也可用于高效富集并分离口腔微生物,有助于提高PCR或NGS检测的准确性(图2)。

作者指出,基于口腔微生物组建立前列腺疾病的早期诊断或预后模型,可为临床诊疗前列腺疾病提供新思路。


图2:前列腺疾病患者的口腔微生物临床检测

结论和展望

综上所述,口腔微生物组对前列腺疾病具有潜在的影响,探究口腔微生物组与前列腺疾病的因果关联,对该疾病的预防和治疗具有重要意义。

作者提出,破译驱动前列腺疾病的特定致病菌群或代谢产物并表征其潜在机制十分必要。此外,靶向菌群的治疗方法也正在兴起,靶向调节口腔菌群可为牙周疾病及前列腺疾病的防治提供新策略。

原始出处:

Cheng Fang, Lan Wu, Cong Zhu, et al.A potential therapeutic strategy for prostatic disease by targeting the oral microbiome.Med Res Rev . 2020 Dec 30.doi: 10.1002/med.21778. 

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    2021-01-08 jyzxjiangqin

    好文章!

    0

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