Department of Neonatology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, PR China; Chongqing Key Laboratory of Child Health and Nutrition, PR China; Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, PR China.
Department of Neonatology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, PR China; Chongqing Key Laboratory of Pediatrics, PR China.
Pharmacol Res. 2020 Oct;160:105082. doi: 10.1016/j.phrs.2020.105082. Epub 2020 Jul 15.
Maternal diet plays a beneficial role in the health, including the neurodevelopment, of offspring. Insufficient fibre consumption among the general population has increased concern about neurocognitive diseases. However, the association between maternal low-fibre diet (MLFD) and neurocognitive function in offspring is still unclear.
Mice were fed diets containing diverse levels of fibre or administered short-chain fatty acids (SCFAs) during gestation. The neurocognitive functions of the offspring and synaptic plasticity-related protein levels were measured. Gene expression was disrupted by siRNA interference. Samples from pregnant women and paired umbilical cord blood (UCB) samples were analysed by the general linear model.
We found that MLFD impaired cognitive function and synaptic plasticity in offspring and that the impairments were reversed by butyrate intake but not propionate intake. Mechanistic studies showed that histone deacetylase (HDAC)-4 is the most likely mediator of butyrate-dependent neurocognitive improvement. In addition, using human maternal serum and paired UCB samples, we demonstrated that SCFA levels in offspring were positively correlated with levels in the maternal serum.
These results provide solid evidence that fibre in the maternal diet regulates neurocognitive functions in offspring through altering SCFA levels and supports the use of SCFA-dependent perinatal intervention for improving offspring health in the clinic.
母体饮食对后代的健康，包括神经发育，起着有益的作用。一般人群中膳食纤维摄入量不足，这增加了对神经认知疾病的担忧。然而，母体低纤维饮食（MLFD）与后代神经认知功能之间的关系尚不清楚。
在妊娠期间，用含有不同纤维水平的饮食喂养小鼠或给予短链脂肪酸（SCFAs）。测量后代的神经认知功能和与突触可塑性相关的蛋白质水平。通过 siRNA 干扰破坏基因表达。通过一般线性模型分析孕妇和配对脐血（UCB）样本。
我们发现 MLFD 损害了后代的认知功能和突触可塑性，而丁酸盐的摄入可以逆转这些损害，但丙酸盐的摄入则不能。机制研究表明，组蛋白去乙酰化酶（HDAC）-4 很可能是丁酸盐依赖的神经认知改善的介导物。此外，使用人母体血清和配对的 UCB 样本，我们证明了后代中的 SCFA 水平与母体血清中的水平呈正相关。
这些结果为纤维在母体饮食中通过改变 SCFA 水平来调节后代神经认知功能提供了确凿的证据，并支持使用 SCFA 依赖性围产期干预措施在临床上改善后代健康。
