School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Food Funct. 2024 Sep 16;15(18):9191-9209. doi: 10.1039/d4fo01723d.
Infant formulas are designed to provide sufficient energy and the necessary nutrients to support the growth and development of newborns. Currently, research on the functions of formula milk powder focuses on clinical research and cell experiments, and there were many cell experiments that investigated the effect of infant formulas on cellular growth. However, most of the cells used are tumor cell lines, which are unable to simulate the real digestion process of an infant. In this study, we innovatively proposed a method that integrates human small intestinal organoids (SIOs) with transcriptomics and metabolomics analysis. We induced directed differentiation of human embryonic stem cells into SIOs and simulated the intestinal environment of newborns with them. Then, three kinds of 1-stage infant formulas from the same brand were introduced to simulate the digestion, absorption, and metabolism of the infant intestine. The nutritional value of each formula milk powder was examined by multi-omics sequencing methods, including transcriptomics and metabolomics analysis. Results showed that there were significant alterations in gene expression and metabolites in the three groups of SIOs after absorbing different infant formulas. By analyzing transcriptome and metabolome data, combined with GO, KEGG, and GSEA analysis, we demonstrated the ability of SIOs to model the different aspects of the developing process of the intestine and discovered the correlation between formula components and their effects, including and lactoferrin. The study reveals the effect and mechanisms of formula milk powder on the growth and development of infant intestines and the formation of immune function. Furthermore, our method can help to construct a multi-level assessment model, detect the effects of nutrients, and evaluate the interactions between nutrients, which is helpful for future research and development of infant powders.
婴儿配方奶粉旨在提供足够的能量和必要的营养物质，以支持新生儿的生长和发育。目前，配方奶粉的功能研究主要集中在临床研究和细胞实验上，有许多细胞实验研究了婴儿配方奶粉对细胞生长的影响。然而，大多数使用的细胞是肿瘤细胞系，无法模拟婴儿的真实消化过程。在这项研究中，我们创新性地提出了一种将人小肠类器官（SIOs）与转录组学和代谢组学分析相结合的方法。我们诱导人胚胎干细胞定向分化为 SIOs，并利用它们模拟新生儿的肠道环境。然后，我们引入了同一种品牌的三种 1 阶段婴儿配方奶粉，以模拟婴儿肠道的消化、吸收和代谢。我们通过多组学测序方法，包括转录组学和代谢组学分析，检查了每种配方奶粉的营养价值。结果表明，在吸收不同婴儿配方奶粉后，三组 SIOs 的基因表达和代谢物都发生了显著变化。通过分析转录组和代谢组数据，并结合 GO、KEGG 和 GSEA 分析，我们证明了 SIOs 能够模拟肠道发育过程的不同方面，并发现了配方成分与其作用之间的相关性，包括乳铁蛋白。该研究揭示了配方奶粉对婴儿肠道生长发育和免疫功能形成的影响及其机制。此外，我们的方法可以帮助构建一个多层次评估模型，检测营养物质的效果，并评估营养物质之间的相互作用，这有助于未来婴儿配方奶粉的研究和开发。
