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development of children. Many infants aged 0\u20136 months are fed with infant formula rather than breast milk. Research on cancer cell lines and animal models is limited to examining the nutrition effects of formula and breast milk, as it does not comprehensively consider absorption, metabolism, and the health and social determinants of the infant and its physiology. Our study utilized small intestine organoids induced from human embryo stem cell (ESC) to compare the nutritional effects of breast milk from five donors during their postpartum lactation period of 1\u20136 months and three types of Stage 1 infant formulae from regular retail stores. Using transcriptomics and untargeted metabolomics approaches, we focused on the differences such as cell growth and development, cell junctions, and extracellular matrix. We also analyzed the roles of pathways including AMPK, Hippo, and Wnt, and identified key genes such as ALPI, SMAD3, TJP1, and WWTR1 for small intestine development. Through observational and in-vitro analysis, our study demonstrates ESC-derived organoids might be a promising model for exploring nutritional effects and underlying mechanisms.<\/jats:p>","DOI":"10.3390\/nu16172951","type":"journal-article","created":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T07:59:40Z","timestamp":1725263980000},"page":"2951","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Multi-Omics Profiles of Small Intestine Organoids in Reaction to Breast Milk and Different Infant Formula Preparations"],"prefix":"10.3390","volume":"16","author":[{"given":"Xianli","family":"Wang","sequence":"first","affiliation":[{"name":"School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3031-7732","authenticated-orcid":false,"given":"Shangzhi","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chengdong","family":"Zheng","sequence":"additional","affiliation":[{"name":"Heilongjiang Firmus Dairy Co., Ltd., C-16, 10A Jiuxianqiao Rd., Chaoyang, Beijing 100015, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3482-9020","authenticated-orcid":false,"given":"Chenxuan","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haiyang","family":"Yao","sequence":"additional","affiliation":[{"name":"School of Medicine, Shanghai Jiao 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China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruihong","family":"Ge","sequence":"additional","affiliation":[{"name":"School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Cheng","sequence":"additional","affiliation":[{"name":"School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanyuan","family":"Yan","sequence":"additional","affiliation":[{"name":"School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6975-0844","authenticated-orcid":false,"given":"Shilong","family":"Jiang","sequence":"additional","affiliation":[{"name":"Heilongjiang Firmus Dairy Co., Ltd., C-16, 10A Jiuxianqiao Rd., Chaoyang, 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Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1017\/S002966510999019X","article-title":"Early nutrition and long-term health: A practical approach: Symposium on \u2018Early nutrition and later disease: Current concepts, research and implications\u2019","volume":"68","author":"Lanigan","year":"2009","journal-title":"Proc. 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