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婴儿双歧杆菌定植改变了无菌成年小鼠的行为。

Postnatal colonization with human "infant-type" Bifidobacterium species alters behavior of adult gnotobiotic mice.

机构信息

Department of Pathology, Texas Children's Hospital, Houston, Texas, United States of America.

Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, United States of America.

出版信息

PLoS One. 2018 May 15;13(5):e0196510. doi: 10.1371/journal.pone.0196510. eCollection 2018.

Abstract

Accumulating studies have defined a role for the intestinal microbiota in modulation of host behavior. Research using gnotobiotic mice emphasizes that early microbial colonization with a complex microbiota (conventionalization) can rescue some of the behavioral abnormalities observed in mice that grow to adulthood completely devoid of bacteria (germ-free mice). However, the human infant and adult microbiomes vary greatly, and effects of the neonatal microbiome on neurodevelopment are currently not well understood. Microbe-mediated modulation of neural circuit patterning in the brain during neurodevelopment may have significant long-term implications that we are only beginning to appreciate. Modulation of the host central nervous system by the early-life microbiota is predicted to have pervasive and lasting effects on brain function and behavior. We sought to replicate this early microbe-host interaction by colonizing gnotobiotic mice at the neonatal stage with a simplified model of the human infant gut microbiota. This model consortium consisted of four "infant-type" Bifidobacterium species known to be commensal members of the human infant microbiota present in high abundance during postnatal development. Germ-free mice and mice neonatally-colonized with a complex, conventional murine microbiota were used for comparison. Motor and non-motor behaviors of the mice were tested at 6-7 weeks of age, and colonization patterns were characterized by 16S ribosomal RNA gene sequencing. Adult germ-free mice were observed to have abnormal memory, sociability, anxiety-like behaviors, and motor performance. Conventionalization at the neonatal stage rescued these behavioral abnormalities, and mice colonized with Bifidobacterium spp. also exhibited important behavioral differences relative to the germ-free controls. The ability of Bifidobacterium spp. to improve the recognition memory of both male and female germ-free mice was a prominent finding. Together, these data demonstrate that the early-life gut microbiome, and human "infant-type" Bifidobacterium species, affect adult behavior in a strongly sex-dependent manner, and can selectively recapitulate the results observed when mice are colonized with a complex microbiota.

摘要

越来越多的研究已经确定了肠道微生物群在调节宿主行为方面的作用。使用无菌小鼠的研究强调,早期用复杂的微生物群(定植)定植可以挽救一些在完全缺乏细菌(无菌小鼠)的情况下长大的小鼠中观察到的行为异常。然而,人类婴儿和成人的微生物组差异很大,新生儿微生物组对神经发育的影响目前还不太清楚。微生物介导的神经发育过程中大脑神经回路模式的调节可能具有重要的长期影响,而我们才刚刚开始意识到这一点。早期微生物群对宿主中枢神经系统的调节预计会对大脑功能和行为产生广泛而持久的影响。我们试图通过在新生儿期用简化的人类婴儿肠道微生物组模型定植无菌小鼠来复制这种早期的微生物-宿主相互作用。该模型联合体由四种“婴儿型”双歧杆菌组成,已知它们是人类婴儿微生物组中的共生成员,在出生后发育过程中大量存在。使用无菌小鼠和在新生儿期定植复杂的常规小鼠微生物组的小鼠进行比较。在 6-7 周龄时测试小鼠的运动和非运动行为,并通过 16S 核糖体 RNA 基因测序来描述定植模式。成年无菌小鼠表现出异常的记忆、社交、焦虑样行为和运动表现。在新生儿期进行定植可挽救这些行为异常,而定植双歧杆菌的小鼠与无菌对照相比也表现出重要的行为差异。双歧杆菌能够改善雄性和雌性无菌小鼠的识别记忆,这是一个突出的发现。总之,这些数据表明,早期的肠道微生物组和人类的“婴儿型”双歧杆菌会以强烈的性别依赖方式影响成年行为,并可以选择性地重现当小鼠用复杂的微生物群定植时观察到的结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/787a/5953436/547d024d10dd/pone.0196510.g001.jpg

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