PDF(Pubmed)
Abstract：
At birth, mammals experience a massive colonization by microorganisms. We previously reported that newborn mice gestated and born germ-free (GF) have increased microglial labeling and alterations in developmental neuronal cell death in the hippocampus and hypothalamus, as well as greater forebrain volume and body weight when compared to conventionally colonized (CC) mice. To test whether these effects are solely due to differences in postnatal microbial exposure, or instead may be programmed in utero, we cross-fostered GF newborns immediately after birth to CC dams (GF→CC) and compared them to offspring fostered within the same microbiota status (CC→CC, GF→GF). Because key developmental events (including microglial colonization and neuronal cell death) shape the brain during the first postnatal week, we collected brains on postnatal day (P) 7. To track gut bacterial colonization, colonic content was also collected and subjected to 16S rRNA qPCR and Illumina sequencing. In the brains of GF→GF mice, we replicated most of the effects seen previously in GF mice. Interestingly, the GF brain phenotype persisted in GF→CC offspring for almost all measures. In contrast, total bacterial load did not differ between the CC→CC and GF→CC groups on P7, and bacterial community composition was also very similar, with a few exceptions. Thus, GF→CC offspring had altered brain development during at least the first 7 days after birth despite a largely normal microbiota. This suggests that prenatal influences of gestating in an altered microbial environment programs neonatal brain development.
摘要：
出生时,哺乳动物经历了大量的微生物定植。我们先前报道了妊娠和出生的无菌（GF）的新生小鼠在海马和下丘脑中的小胶质细胞标记和发育神经元细胞死亡的改变。以及与常规定殖（CC）小鼠相比更大的前脑体积和体重。为了测试这些影响是否仅仅是由于出生后微生物暴露的差异，或者可以在子宫内编程，我们在出生后立即将GF新生儿交叉培养到CC水坝（GF→CC），并将它们与相同微生物群状态下培养的后代进行比较（CC→CC，GF→GF)。因为关键的发育事件（包括小胶质细胞定植和神经元细胞死亡）在出生后的第一周塑造了大脑，我们在出生后第7天收集大脑。为了追踪肠道细菌定植，还收集结肠内容物并进行16SrRNAqPCR和Illumina测序。在GF→GF小鼠的大脑中，我们复制了以前在GF小鼠中看到的大多数效应。有趣的是,在几乎所有测量中，GF脑表型在GF→CC后代中持续存在。相比之下,P7上CC→CC和GF→CC组之间的总细菌负荷没有差异，细菌群落组成也非常相似，除了少数例外。因此，尽管微生物群基本正常，但GF→CC后代至少在出生后的前7天改变了大脑发育。这表明在改变的微生物环境中妊娠的产前影响会规划新生儿的大脑发育。
