Cell Host & Microbe:肠道共生菌群副产物可帮助抵御沙门氏菌

2018-07-30 责编:风铃 生物探索

一提到细菌,人们就会想起沙门氏菌、结核杆菌等很多导致疾病的罪魁祸首,但细菌也不全都是有害的,人体肠道内就有很多益生菌一直在默默守护着我们,它们可以帮助消化食物、分泌一些我们不能合成的营养素,增强我们的免疫力等。近日,斯坦福大学的科学家们还发现,肠道菌群分泌的副产物可以帮助抵御致病的沙门氏菌。

一提到细菌,人们就会想起沙门氏菌、结核杆菌等很多导致疾病的罪魁祸首,但细菌也不全都是有害的,人体肠道内就有很多益生菌一直在默默守护着我们,它们可以帮助消化食物、分泌一些我们不能合成的营养素,增强我们的免疫力等。近日,斯坦福大学的科学家们还发现,肠道菌群分泌的副产物可以帮助抵御致病的沙门氏菌。

沙门氏菌感染常常会引起感染者腹泻,发烧和腹部绞痛,大多数病例是由受污染的食物引起的。根据美国疾病控制和预防中心的数据,沙门氏菌每年导致大约120万例疾病,其中23,000例住院,450例死亡。

美国斯坦福大学医学院的研究人员近日发现了一种由肠道共生菌群分泌的副产物,可以帮助抵御沙门氏菌。该研究成果于2018年7月26日在线发表于Cell子刊 《Cell Host & Microbe》杂志上。

“人类对细菌感染的反应不同:有些人感染了细菌,有些人却没有感染;有些人因此患病了,有些人却保持健康;有些人会传播细菌,有些人却可以将细菌清除。”微生物学和免疫学教授,该论文的通讯作者Denise Monack博士说,“这些差异存在的原因一直是一个谜,而我们的发现可能会揭开这一谜团。”

Denise Monack博士带领的研究团队从一项多年来在该领域得到认可的观察开始着手:两种近交系小鼠在被病原体感染后,其肠道中含有不同水平的沙门氏菌。 “最大的挑战是确定为什么会发生这种情况,”论文第一作者,Amanda Jacobson博士说。

首先,研究人员通过进行粪便移植实验,确定沙门氏菌生长的差异可归因于每种小鼠肠道中细菌的天然组成。他们先给予小鼠抗生素以杀死其正常的肠道细菌,然后用其他小鼠的粪便替换这些小鼠的肠道微生物群落,结果发现,其中一些小鼠对沙门氏菌感染具有了抗性。随后,研究人员通过使用机器学习工具分析不同菌群中菌株的不同,来确定哪些微生物与沙门氏菌感染的抵抗力增加有关。

最后,他们找到了一种特殊的细菌,拟杆菌(Bacteroides),这种细菌在移植了对沙门氏菌具有保护作用的微生物群的小鼠肠道中更为丰富。拟杆菌在代谢过程中会产生短链脂肪酸,如甲酸盐,乙酸盐,丁酸盐和丙酸盐,并且在保护沙门氏菌生长的小鼠中丙酸盐水平会高三倍。

在随后的研究中,他们发现该丙酸盐对沙门氏菌的生长有直接的影响:丙酸盐会显着降低细胞内pH值,从而增加细菌开始分裂和生长所需的时间,并最终抑制了沙门氏菌的生长。

“总的来说,我们的研究结果表明,当拟杆菌产生的丙酸盐浓度很高时,沙门氏菌不能提高其内部pH值,以启动促进其生长所需的细胞功能,”Amanda Jacobson博士说, “当然,我们想知道这在人类身上是不是也能起到相同的作用,接下来的研究步骤将包括确定小分子丙酸的基本生物学特性以及它如何在分子水平上起作用。”

治疗沙门氏菌感染有时需要使用抗生素,但这可能会使沙门氏菌引起的疾病或食物中毒病情变得更糟,因为它们也会杀死保持肠道健康的“好”细菌。而使用丙酸盐治疗这些感染可以克服这种局限。对此,Monack还补充说:“减少抗生素的使用是丙酸盐带来的一个额外的好处,因为过量使用抗生素会增加微生物耐药的风险。”

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    2019-06-07 xjy02
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    2019-01-30 智慧医人
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