《自然》封面:最大规模研究揭示婴儿肠道微生物发展的三个阶段

对于肠道微生物,有一个让人难以想象的事实:人体肠道内寄生着 10 万亿个细菌,是一个成年人自身的细胞数量的 10 倍!正常情况下人拉出的“粑粑”,除去水分的固体物中约有 50% 都是细菌的“尸体”。

肠道微生物对人体健康的影响也越来越受关注,肠道微生物也已经成为炙手可热的研究领域。科学家们已经发现,这些寄生在肠道中的微生物,在人体多种生理生化功能中发挥着重要作用。比如,它们能够影响体重和消化能力、能够抵御感染、影响自体免疫疾病的患病风险,甚至还会控制人体对癌症治疗药物的效果。

但是,对于肠道微生物与疾病健康的关联,仍然充满了未知,肠道微生物对于更多人类疾病中的作用仍然不清楚。

10 月 24 日,全球顶级期刊《自然》杂志背靠背发表两篇重磅文章,揭示了肠道微生物在婴幼儿阶段发展和影响的“秘密”。

《自然》封面:最大规模研究揭示婴儿肠道微生物发展的三个阶段

图 | 10 月 25 日《自然》杂志封面(来源:nature.com)

第一篇题为《根据 TEDDY 研究看儿童早期肠道微生物的发育(Temporal development of the gut microbiome in early childhood from the TEDDY study)》的论文,是迄今为止最大规模婴幼儿临床微生物的研究。来自美国贝勒医学院研究人员领导的研究团队,通过 TEDDY(青少年糖尿病环境决定因素)研究中的数据,对 903 名 3 至 46 个月大儿童 12500 份粪便样本的肠道微生物进行测序分析。

利用最先进的 RNA 和 DNA 测序技术,研究人员揭示婴幼儿的肠道菌群经历了三个不同的进展阶段:发育阶段(3-14 个月龄),过渡阶段(15-30 个月龄)和稳定阶段(31-46 个月龄)。

“我们知道,生命最初几年对于肠道菌群的建立非常重要。一个人刚生下来时只有很少的微生物,但在生命的最初阶段肠道微生物会很快聚集在体内。”贝勒医学院 Alkek 宏基因组学与微生物研究中心主任 Joseph Petrosino 博士说,“在这项研究中,我们仔细研究了生命最初几年微生物群的建立以及与这一系列事件相关的早期生命暴露。”

研究发现,至少部分母乳喂养与较高丰度的短双歧杆菌(Bifidobacterium breve)和两歧双歧杆菌(Bifidobacterium bifidum)之间存在关联。这两种细菌具有益生菌特性,已知在生命早期广泛存在。

《自然》封面:最大规模研究揭示婴儿肠道微生物发展的三个阶段

(来源: www.pixabay.com)

此外,停止母乳喂养会加速婴幼儿肠道菌群的成熟。一旦停止母乳喂养,婴幼儿体内那些具有处理人乳能力的双歧杆菌菌株就会消失,不具备处理母乳代谢物能力的双歧杆菌菌株就会生长,并体现出较高丰富的厚壁菌门细菌。这也这意味着停止母乳喂养后婴幼儿的肠道菌群会迅速通过其它阶段进入稳定阶段。

Petrosino 表示,“这提供了早期饮食如何影响肠道菌群发展的见解,进一步的研究将有助于更好地理解加速肠道菌群成熟速度的影响。”

此外,研究人员还揭示了不同分娩方式对婴幼儿肠道菌群的影响。在那些经阴道分娩的婴幼儿肠道内,拥有更丰富的拟杆菌属细菌。并且这些婴幼儿往往在生命的前 40 个月会拥有更多的肠道微生物。

“这些信息对于未来用于科学发现和潜在干预目的的婴幼儿群体肠道菌群研究非常有用。我们这种通过对菌群发展分阶段的方式可以为研究人员提供额外的解决方案,以揭示可能与疾病相关的差异。”Petrosino 说。

《自然》封面:最大规模研究揭示婴儿肠道微生物发展的三个阶段

(来源:wikipedia)

TEDDY 研究已经收集了近 10 年来包括美国和欧洲的六个临床研究中心,涉及数千名具有 1 型糖尿病(T1D)遗传易感性或 T1D 患者一级亲属的新生儿,目的就是了解导致青少年 1 型糖尿病遗传风险增加的原因。

所以在《自然》杂志同期发表的第二篇题为《根据 TEDDY 研究看早发 1 型糖尿病肠道菌群(The human gut microbiome in early-onset type 1 diabetes from the TEDDY study)》的研究中,由哈佛医学院医学教授 Ramnik Xavier 领导的团队,则揭示了肠道微生物与青少年 1 型糖尿病之间的关联。

《自然》封面:最大规模研究揭示婴儿肠道微生物发展的三个阶段

(来源:prensalibre.com)

研究人员分析了参与 TEDDY 研究的 783 名儿童粪便样本中的 10913 个宏基因组(所有微生物菌群基因组的总和),这些样本从婴幼儿 3 个月大开始,每个月收集一次,直到临床终点(发生胰岛自身免疫或 T1D)。

研究小组发现,对照儿童的肠道菌群中含有更多与发酵和短链脂肪酸生物合成相关的基因。这表明,制备短链脂肪酸的肠道微生物功能在早发 T1D 的保护作用方面发挥着重要作用。

贝勒医学院的 Christopher J. Stewart 博士说:“这些初步分析加强了以前的相关研究,并在生命的关键时期揭示了重要的微生物组合。该研究的发现将为接下来的工作铺平道路,以阐明肠道菌群如何影响健康和疾病,特别是 1 型糖尿病。”

参考:

https://www.nature.com/articles/s41586-018-0617-x

https://www.nature.com/nature/volumes/562/issues/7728

https://www.sciencedaily.com/releases/2018/10/181024131304.htm

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