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转录组和代谢组分析揭示了配方奶和母乳对人小肠类器官生长发育的影响。

Transcriptome and metabolome analyses reveal the effects of formula and breast milk on the growth and development of human small intestinal organoids.

机构信息

School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

出版信息

Food Res Int. 2024 Nov;195:114999. doi: 10.1016/j.foodres.2024.114999. Epub 2024 Aug 25.

DOI:10.1016/j.foodres.2024.114999
PMID:39277258
Abstract

Breast milk is widely acknowledged as the ideal nutritional resource for infants and can well meet the nutritional requirements for baby's growth and development. Infant formula is a substitute for breast milk, designed to closely mimic its composition and function for breast milk. Most of the previous studies used tumor colorectal cancer cell lines to study the nutritional potency of formula and its components, so realistic data closer to the baby could not be obtained. Small intestinal organoids, derived from differentiated human embryonic stem cells, can be used to simulate nutrient absorption and metabolism in vitro. In this experiment, we used small intestinal organoids to compare the nutrient absorption and metabolism of three infant formulae for 0-6 months with breast milk samples. Transcriptome and metabolome sequencing methods were used to analyze the differentially expressed genes (DEGs) and differentially expressed metabolites (DEMs). The pathways related to DEGs, DEMs were enriched using GO, KEGG, GSEA and other methods to investigate their biological characteristics. We have found that both formula and breast milk promote the development of the infant's immune system, nutrient absorption and intestinal development. In PMH1 we found that the addition of oligofructose to milk powder promoted lipid metabolism and absorption. In PMH2 we found that whey protein powder favours the development of the immune system in infants. In PMH3 we found that oligogalactans may act on the brain-gut axis by regulating the intestinal flora, thereby promoting axon formation and neural development. By linking these biological properties of the milk powder with its composition, we confirmed the effects of added ingredients on the growth and development of infants. Also, we demonstrated the validity of small intestine organoids as a model for absorption and digestion in vitro. Through the above analyses, the advantages and disadvantages of the roles of formula and breast milk in the growth and metabolism of infants were also compared.

摘要

母乳被广泛认为是婴儿的理想营养来源,可以很好地满足婴儿生长发育的营养需求。婴儿配方奶粉是母乳的替代品,旨在模拟其成分和功能。之前的大多数研究都使用结直肠癌细胞系来研究配方奶粉及其成分的营养效力,因此无法获得更接近婴儿的实际数据。从小肠类器官分化的人类胚胎干细胞,可以用来模拟体外的营养吸收和代谢。在这项实验中,我们使用小肠类器官来比较三种 0-6 个月婴儿配方奶粉与母乳样本的营养吸收和代谢。使用转录组和代谢组测序方法分析差异表达基因 (DEGs) 和差异表达代谢物 (DEMs)。使用 GO、KEGG、GSEA 等方法对与 DEGs、DEMs 相关的途径进行富集,以研究其生物学特性。我们发现,配方奶和母乳都能促进婴儿免疫系统、营养吸收和肠道发育。在 PMH1 中,我们发现在奶粉中添加低聚果糖可以促进脂类代谢和吸收。在 PMH2 中,我们发现乳清蛋白粉有利于婴儿免疫系统的发育。在 PMH3 中,我们发现低聚半乳糖可能通过调节肠道菌群作用于脑肠轴,从而促进轴突形成和神经发育。通过将配方奶粉的这些生物学特性与其成分联系起来,我们证实了添加成分对婴儿生长发育的影响。此外,我们还证明了小肠类器官作为体外吸收和消化模型的有效性。通过以上分析,比较了配方奶和母乳在婴儿生长和代谢中的作用的优缺点。

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