移植肠道细菌会改变抑郁症相关行为,brain inflammation in animals

科学家已经证明移植肠道细菌,从易受社会压力影响的动物到无压力动物,可能导致收件人的脆弱行为。这项研究揭示了大脑和肠道之间生物相互作用的细节,有一天可能导致对人类精神疾病(如抑郁症)的益生菌治疗。

"In rats that show depressive-type behavior in a laboratory test,研究负责人Seema Bhatnagar说:“我们发现压力会改变他们的肠道微生物群——肠道中细菌的数量。”PhD,麻醉与重症监护科的神经学家费城儿童医院(CHOP).此外,when we transplanted bacteria from those stress-vulnerable rats into rats that had not been stressed,the recipient animals showed similar behavior."

Bhatnagar added that stress also increased inflammation in the brains of vulnerable rats,而且,这种炎症发生在从易受伤害的动物身上移植的无应激大鼠身上。

The study team published its findings online March 4,2019英寸Molecular Psychiatry.

Bhatnagar在CHOP领导压力神经生物学项目,她的许多合著者都是PennCHOP Microbiome Program,a collaboration between researchers at CHOP and the Perelman School of Medicine at the University of Pennsylvania.该项目旨在更好地了解人体内的微生物群落,并改变其特性以改善人体健康。淳于朝PhD,关于那个项目,进行了微生物组数据分析,是本文的合著者。

科学家们已经知道大脑和肠道相互影响。在人类中,patients with psychiatric disorders have different populations of gut microbes compared to microbes in healthy individuals,在精神病动物模型中也发现了类似的发现。这项研究调查了与大脑炎症相关的机制,microbiomes and stress.

"Humans do not all react identically to the same stresses–some are more vulnerable than others to vwin手机版developing psychiatric disorders,others are more resilient," said Bhatnagar."Something similar happens in laboratory animals as well."

In rodents,social hierarchies and territoriality are major sources of stress.在实验室里,researchers model stressors with validated behavioral tools such as a forced swim test or a social defeat test to examine how animals use coping strategies to deal with stress.被动应对的老鼠更容易受到压力的影响,因为它们也表现出更多的焦虑和抑郁类型的行为。而更积极地应对的老鼠对社会压力的影响是有弹性的。Based on these assessments,研究人员将这些动物归类为易受伤害或有弹性的。

The study team then analyzed the fecal microbiomes of vulnerable rats,弹性大鼠a non-stressed control group,and a placebo group.They found that vulnerable rats had higher proportions of certain bacteria,如梭菌,比其他组要多。

然后,他们从三个供体组——易受伤害的大鼠身上进行了粪便移植,弹性大鼠或对照无应激大鼠——转化为无应激大鼠,没有受到压力的动物。他们发现不同的微生物群改变了抑郁样行为。接受易受伤害大鼠移植的大鼠更容易采取抑郁样行为,而接受弹性动物或非应激动物移植的大鼠在行为或神经测量方面没有表现出任何变化。受试者的大脑炎症过程模式也与易受伤害动物的大脑相似,提示肠道细菌如梭状芽孢杆菌的免疫调节作用可能促进了这种炎症。However,移植并没有显著改变焦虑样行为。

The finding that gut transplants from vulnerable rats increased depressive-type behavior but not anxiety-type behavior in non-stressed recipients may point to different mechanisms.The authors said this difference suggests that depressive-type behaviors are more regulated by the gut microbiome,whereas anxiety-type behaviors are primarily influenced by neural activity changes produced by stress experience.

“尽管还需要做更多的研究,we can envision future applications in which we could leverage knowledge of microbiome-brain interactions to treat human psychiatric disorders," said Bhatnagar.“人们已经开始接受非处方益生菌作为补充。如果我们最终能证实特定细菌的有益行为效应,我们可以为新的精神病治疗打下基础。”

这项研究的资金支持来自国防高级研究计划署(DARPA)和美国。陆军研究办公室。

Jiah Pearson-Leary et al,"The gut microbiome regulates the increases in depressive-type behaviors and in inflammatory processes in the ventral hippocampus of stress vulnerable rats,"Molecular Psychiatry,3月4日,2019。https://doi.org/10。1038/s41380-019-0380-x

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