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Cell Rep:肠道微生物大规模宏基因组研究突破,助力治疗心血管疾病!

2020-03-19 MedSci原创 MedSci原创

导语:肠道菌群是一个动态且高度多样化的微生物生态系统,会影响宿主生理的许多方面,虽然许多研究侧重于单个微生物分类群对机体健康的影响,但它们的整体代谢潜力尚未得到充分的探索。

导语:肠道菌群是一个动态且高度多样化的微生物生态系统,会影响宿主生理的许多方面,虽然许多研究侧重于单个微生物分类群对机体健康的影响,但它们的整体代谢潜力尚未得到充分的探索。
 
近日,《Cell Reports》发表一篇文章中,用整合的宏基因组目录对小鼠的肠道微生物进行了全面地研究,通过互补方法重建大量MAG(超基因组组装基因组)以及将16S rRNA基因序列连接到iMAG的无簇构建基因目录,为基于测序的工作提供了高度集成的资源,并将使未来的研究能够探索分类学、功能学以及小鼠肠道和其他生态系统的群落结构更加深入。
 
 
宏基因组(Metagenomics)是一种直接对微生物群体中包含的全部基因组信息进行研究的方法,能更真实的反映样本中微生物组成,在基因功能、代谢通路挖掘方面具有很大优势。基于三代测序的宏基因组分析,能快速精准的获得微生物信息,提高组装的完整度,注释的精确度,是今后微生物研究的新趋势。
 
大规模宏基因组学方法面临的一个具体挑战是将特定的16S rRNA基因序列与MAG连接起来,在此次研究中,研究人员提出了一种综合的方法和相应的计算流程来构建整合的基因目录,显着改善了基因条目的分类学分辨率,并将基因链接到MAGs和重建的全长16S rRNA基因。从298个公共可用的和新测序的元基因组样本构建了整合型小鼠肠道元基因组目录(iMGMC)。此外,他们还提出了一组另外的MAG,它们是从898个宏基因组测序样品的单独单样品组装中获得的,与整合到iMGMC中的MAG一起组成了1,296种细菌水平的细菌基因组。
 
重建的16S rRNA基因与MAG的链接方法
 
在这次分析中,大规模宏基因组组合揭示了数百种小鼠微生物物种,且在小鼠肠道中发现的大多数微生物都是生态系统特有的。最重要的是,整合基因目录和微生物基因组创造了一个综合资源,为今后的进一步探索工作奠定了基础。
 
人肠道中的微生物类群和人自身是一个共同体,是二者共同长期进化的结果,它们的存在和人的健康息息相关。肠道微生物在疾病治疗方面也具有极大的应用前景。克利夫兰诊所的研究人员发现一种肠道微生物——苯乙酰谷氨酰胺(PAG)——与心血管疾病的发展有关,包括心脏病、中风等疾病。这项研究已同步发表在《细胞》杂志上。
 
苯丙氨酸是许多食物中的氨基酸,包括基于植物和动物的蛋白质来源,例如肉,豆和大豆。当苯丙氨酸被肠道中的微生物分解时,会产生副产物(代谢产物),最终到全身的血液循环,称为苯乙酰谷氨酰胺(PAG),是心脏病的危险因素之一。血液中PAG的含量以多种不同方式增加了患心血管疾病的风险。
 
在本次研究中,他们分析了超过3000名患者的样本,发现PAGln水平升高与心脏病发作和中风等不良心脏事件,以及2型糖尿病心血管疾病的独立危险因素)密切相关,且动物模型和微生物移植研究表明,肠道微生物产生的PAG在驱动心血管疾病中起着重要作用。
 
研究人员还分析了全血、富含血小板的血浆和从患者样本中分离出的血小板,以了解PAG如何影响细胞代谢过程。接下来,黑森博士和他的团队在损伤的动物模型中发现,PAG增强了血小板的反应性和凝血潜能,从而增加了血栓的可能性,而血栓是心脏病发作和中风等不良心脏事件的主要危险因素。
 
有趣的是,研究人员还发现,PAG可与β受体阻滞剂(一种常用来治疗心脏病的药物)的受体结合。将β受体阻滞剂应用于升高的PAG动物模型,可以逆转由PAG驱动的心血管终点。此外,研究人员发现,使用基因编辑技术或药物阻断PAG受体信号可显着降低凝血活性。
 
从肠道微生物出发,为治疗心血管疾病提供了新思路,或许我们也可以举一反三,为人类健康的发展找到更多的线索。无论宏观或是微观,肠道微生物仍然有许多值得人类继续探索的地方。
 
原始出处:
 
Till R. Lesker, Abilash C. Durairaj, Eric J.C. Gálvez, et.al. An Integrated Metagenome Catalog Reveals New Insights into the Murine Gut Microbiome. Cell Reports VOLUME 30, ISSUE 9, P2909-2922.E6, MARCH 03, 2020

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    2020-09-26 docwu2019
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    2020-09-12 docwu2019
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高度传染性的诺如病毒会引起腹泻和呕吐,并且因迅速在人口密集的空间中传播而臭名昭着。每年该病毒造成大约200,000人死亡,其中大多数是在发展中国家。然而,目前仍没有针对这种肠道病毒的治疗方法。

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母乳喂养长期以来一直备受推崇,因为母乳除了提供必要的营养外还能够保护婴儿免受某些感染。

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