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母亲的饮食很重要:小鼠的母体益生元摄入可减少焦虑,并改变后代的大脑基因表达和粪便微生物组。

Mom's diet matters: Maternal prebiotic intake in mice reduces anxiety and alters brain gene expression and the fecal microbiome in offspring.

机构信息

Department of Psychiatry, University of Oxford, Warneford Hospital, Warneford Lane, Oxford OX3 7JX, UK.

Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK.

出版信息

Brain Behav Immun. 2021 Jan;91:230-244. doi: 10.1016/j.bbi.2020.09.034. Epub 2020 Oct 5.

Abstract

Compelling evidence links enteric microbes to brain function and behavior. Galacto-oligosaccharide prebiotics have been shown to modulate the composition of gut flora and induce metabolic, neurochemical, and behavioral changes in adult rodents. Despite the brain being most susceptible to environmental factors, such as nutrients and toxins, during the earliest stages of development, it is unknown whether maternal prebiotic supplementation during gestation and lactation influences the offspring gut microbiome, brain, or behavior. The aim of this study was to test whether maternal galacto-oligosaccharide intake during pregnancy and lactation alters the brain and behavior in naïve and endotoxin-challenged offspring. CD1 female mice received either normal drinking water or water supplemented with Bimuno® galacto-oligosaccharides (B-GOS) during gestation and suckling. Offspring behavior was tested at weaning age or adulthood, and a cross-foster design was employed in a separate cohort to differentiate between effects of prenatal and postnatal maternal B-GOS intake. Lipopolysaccharide was also administered to pups at postnatal day 9 to determine whether maternal B-GOS influences the neurobiological and behavioral effects of a neonatal pro-inflammatory challenge in adulthood. Fecal microbiome composition and metabolites were analyzed to explore potential relationships between the maternal microbiome, the offspring gut microbiome, and the offspring brain and behavior. Maternal B-GOS supplementation increased exploratory behavior and reduced expression of hippocampal glutamate receptor genes in young, weaning-age offspring. In addition, postnatal, but not prenatal, B-GOS supplementation increased fecal butyrate and propionate levels. Finally, in adult offspring, perinatal B-GOS intake increased cortical glutamate receptor subunits in females, increased social preference, and reduced anxiety. We provide novel and comprehensive evidence for the influence of maternal prebiotic intake on offspring behavior, brain gene expression, and gut microbiome composition in mice.

摘要

有强有力的证据表明肠道微生物与大脑功能和行为有关。研究表明,半乳糖寡糖益生元可以调节肠道菌群的组成,并在成年啮齿动物中诱导代谢、神经化学和行为变化。尽管大脑在发育的早期阶段最容易受到环境因素(如营养物质和毒素)的影响,但目前尚不清楚母体在妊娠和哺乳期补充益生元是否会影响后代的肠道微生物群、大脑或行为。本研究旨在测试母体在妊娠和哺乳期摄入半乳糖寡糖是否会改变未受挑战和内毒素挑战的后代的大脑和行为。CD1 雌性小鼠在妊娠和哺乳期分别接受普通饮用水或添加 Bimuno®半乳糖寡糖(B-GOS)的饮用水。在断奶或成年时测试后代的行为,并在另一组中采用交叉寄养设计来区分产前和产后母体 B-GOS 摄入的影响。在产后第 9 天还向幼崽中注射脂多糖,以确定母体 B-GOS 是否影响成年期新生炎症挑战的神经生物学和行为影响。分析粪便微生物组组成和代谢物,以探索母体微生物组、后代肠道微生物组和后代大脑和行为之间的潜在关系。母体 B-GOS 补充增加了年轻、断奶期后代的探索行为,并降低了海马谷氨酸受体基因的表达。此外,产后而非产前 B-GOS 补充增加了粪便中丁酸和丙酸的水平。最后,在成年后代中,围产期 B-GOS 摄入增加了雌性皮质谷氨酸受体亚基的表达,增加了社交偏好,并降低了焦虑。本研究为母体益生元摄入对小鼠后代行为、大脑基因表达和肠道微生物组组成的影响提供了新的、全面的证据。

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