利用整合转录组学和代谢组学探索婴儿配方奶粉对小肠类器官生长发育的影响。
Using integrated transcriptomics and metabolomics to explore the effects of infant formula on the growth and development of small intestinal organoids.
发表日期:2024 Aug 19
作者:
Xianli Wang, Yuxin Jing, Chengdong Zheng, Chenxuan Huang, Haiyang Yao, Zimo Guo, Yilun Wu, Zening Wang, Zhengyang Wu, Ruihong Ge, Wei Cheng, Yuanyuan Yan, Shilong Jiang, Jianguo Sun, Jingquan Li, Qinggang Xie, Xiaoguang Li, Hui Wang
来源:
Stem Cell Research & Therapy
摘要:
婴儿配方奶粉旨在提供充足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,对配方奶粉功能的研究主要集中在临床研究和细胞实验上,有很多细胞实验研究婴儿配方奶粉对细胞生长的影响。然而,所使用的细胞大多是肿瘤细胞系,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类小肠类器官(SIO)与转录组学和代谢组学分析相结合的方法。我们诱导人类胚胎干细胞定向分化为 SIO,并用它们模拟新生儿的肠道环境。随后,又推出了同品牌的三种一阶段婴儿配方奶粉,模拟婴儿肠道的消化、吸收和代谢。通过多组学测序方法,包括转录组学和代谢组学分析,检测每种配方奶粉的营养价值。结果显示,三组SIO在吸收不同婴儿配方奶粉后,基因表达和代谢物均出现显着变化。通过分析转录组和代谢组数据,结合 GO、KEGG 和 GSEA 分析,我们证明了 SIO 能够模拟肠道发育过程的不同方面,并发现配方成分及其效果之间的相关性,包括乳酸菌和乳铁蛋白。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机制。此外,我们的方法可以帮助构建多层次的评估模型,检测营养素的作用,并评估营养素之间的相互作用,这有助于未来婴儿奶粉的研究和开发。
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 Lactobacillus lactis 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.