Using integrated transcriptomics and metabolomics to explore the effects of infant formula on the growth and development of small intestinal organoids

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.