Breast milk plays an essential role for offspring development; however, there lacks evidence of how specific milk components like nucleic acids mechanistically function to regulate neonate development. Previously, we found that maternal high-fat diet (HFD) not only significantly affected mRNA and miRNA content of the secreted milk transcriptome in mice but also affected the duodenal proteome of suckling pups. Here, we hypothesized that nucleic acids differentially expressed in milk of HFD fed dams are related to differentially abundant proteins in offspring duodenum nursed by HFD dams. We tested this hypothesis by analyzing one-to-one relationships in RNA-seq data of milk transcriptomes from control (10% kcal fat) and HFD (60% kcal fat) fed mice and liquid chromatography–tandem mass spectrometry (LC-MS/MS) duodenal proteome data from pups exposed to milk. Ten percent of differentially abundant duodenal proteins between controls and HFD-exposed pups had predicted upregulation or downregulation based on differential milk RNA content. Of these, 76% were targets of upregulated miRNA, and linear regression analysis indicated relationships (p < 0.05) between multiple milk miRNA counts and duodenal protein abundance. Duodenal proteins that were potential targets of milk miRNA enriched Gene Ontology (GO) terms and KEGG pathways related to cytoskeletal structure and neural development, suggesting potential regulation of pup enteric nervous system. One-to-one relationships between milk miRNA content and protein abundance in neonate duodenum support the potential for milk miRNAs regulating neonate development. Identification of milk miRNAs that changed in response to maternal diet will enable design of mechanistic studies that test effects on neonate.

中文翻译：

---

新生儿十二指肠中牛奶miRNA含量与蛋白质丰度之间的一对一关系支持了牛奶miRNA调节新生儿发育的潜力。

母乳对后代的发育起着至关重要的作用。然而，缺乏证据证明特定的乳成分（如核酸）如何在机制上调节新生儿的发育。以前，我们发现母体高脂饮食（HFD）不仅会显着影响小鼠分泌乳转录组的mRNA和miRNA含量，而且还会影响乳幼儿十二指肠蛋白质组。在这里，我们假设HFD喂养大坝牛奶中差异表达的核酸与HFD大坝哺育的后代十二指肠中差异丰富的蛋白质有关。我们通过分析喂养（10％kcal脂肪）和HFD（60％kcal脂肪）喂养的小鼠的牛奶转录组的RNA-seq数据与液相色谱-串联质谱法（LC-MS / MS）来自暴露于牛奶的幼仔的十二指肠蛋白质组数据。对照和暴露于HFD的幼仔之间，十二指肠蛋白质差异丰富，其中百分之十的蛋白质根据差异的牛奶RNA含量预测上调或下调。其中76％是miRNA上调的靶标，线性回归分析显示了相关性（p > 0.05）在多个牛奶miRNA计数与十二指肠蛋白丰度之间。十二指肠蛋白是牛奶miRNA富集的基因本体论（GO）术语和与细胞骨架结构和神经发育有关的KEGG途径的潜在靶标，表明可能对小肠肠道神经系统进行调节。新生儿十二指肠中牛奶miRNA含量与蛋白质丰度之间的一对一关系支持牛奶miRNA调节新生儿发育的潜力。鉴定因母体饮食而变化的牛奶miRNA，将有助于设计可测试对新生儿影响的机制研究。