{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:46:29Z","timestamp":1782279989173,"version":"3.54.5"},"reference-count":123,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:p>\n                    Digestion in the small intestine is a crucial step in the breakdown and absorption of nutrients from human milk.\n                    <jats:italic>In vitro<\/jats:italic>\n                    models of intestinal digestion are commonly employed to investigate the digestion behaviour of breast milk nutrients. Accurate replication of the infant small intestine requires a detailed understanding of its biochemical environment. This review summarises current knowledge on small intestinal digestion in infants, integrating evidence from both human studies and\n                    <jats:italic>in vitro<\/jats:italic>\n                    intestinal digestion models. Key challenges in simulating the infant small intestinal conditions, including motility, intestinal fluid dynamics and composition, enzymatic activity, and absorption are discussed. This literature review also provides recommendations for enhancing the physiological relevance of\n                    <jats:italic>in vitro<\/jats:italic>\n                    small intestinal digestion systems for studying intestinal digestion in early infancy.\n                  <\/jats:p>","DOI":"10.3389\/fnut.2026.1826318","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T04:49:17Z","timestamp":1782276557000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Simulating the biochemical environment for infant intestinal digestion: key challenges and recommendations"],"prefix":"10.3389","volume":"13","author":[{"given":"Linda","family":"Nezbedova","sequence":"first","affiliation":[{"name":"Riddet Institute, Massey University","place":["Palmerston North, New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiqian","family":"Ye","sequence":"additional","affiliation":[{"name":"Riddet Institute, Massey University","place":["Palmerston North, New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandra","family":"Acevedo-Fani","sequence":"additional","affiliation":[{"name":"Riddet Institute, Massey University","place":["Palmerston North, New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Brough","sequence":"additional","affiliation":[{"name":"School of Food Technology and Natural Sciences, Massey University","place":["Palmerston North, New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harjinder","family":"Singh","sequence":"additional","affiliation":[{"name":"Riddet Institute, Massey University","place":["Palmerston North, New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debashree","family":"Roy","sequence":"additional","affiliation":[{"name":"Riddet Institute, Massey University","place":["Palmerston North, New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1080\/10408398.2021.1957765","article-title":"Understanding protein digestion in infants and the elderly: current in vitro digestion models","volume":"63","author":"Lee","year":"2023","journal-title":"Crit Rev Food Sci Nutr"},{"key":"ref2","article-title":"Global strategy for infant and young child feeding","year":"2003"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1700231","DOI":"10.1002\/mnfr.201700231","article-title":"Protein digestion of baby foods: study approaches and implications for infant health","volume":"62","author":"Gan","year":"2018","journal-title":"Mol Nutr Food Res"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"100984","DOI":"10.1016\/j.cofs.2022.100984","article-title":"Challenges in simulating the biochemical environment of the infant stomach to assess the gastric digestion of infant formulae","volume":"50","author":"Wang","year":"2023","journal-title":"Curr Opin Food Sci"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1177\/0115426507022002159","article-title":"Development of the infant intestine: implications for nutrition support","volume":"22","author":"Commare","year":"2007","journal-title":"Nutr Clin Pract"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1016\/j.earlhumdev.2007.09.009","article-title":"Gastrointestinal maturation and implications for infant feeding","volume":"83","author":"Neu","year":"2007","journal-title":"Early Hum Dev"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1093\/ajcn\/37.1.52","article-title":"Comparison of the gastrointestinal growth- promoting effects of rat colostrum and mature milk in newborn rats in vivo","volume":"37","author":"Berseth","year":"1983","journal-title":"Am J Clin Nutr"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"G662","DOI":"10.1152\/ajpgi.1987.253.5.G662","article-title":"Enhancement of intestinal growth in neonatal rats by epidermal growth factor in milk","volume":"253","author":"Berseth","year":"1987","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"ref9","first-page":"272","article-title":"Changes in the organs of pigs in response to feeding for the first 24 h after birth: II. The digestive tract","volume":"28","author":"Widdowson","year":"1976","journal-title":"Neonatol"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1079\/PNS19760056","article-title":"Cellular growth and function","volume":"35","author":"Widdowson","year":"1976","journal-title":"Proc Nutr Soc"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1016\/j.foodchem.2013.09.036","article-title":"Validation of a new in vitro dynamic system to simulate infant digestion","volume":"145","author":"M\u00e9nard","year":"2014","journal-title":"Food Chem"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.foodres.2015.11.022","article-title":"Holder pasteurization impacts the proteolysis, lipolysis and disintegration of human milk under in vitro dynamic term newborn digestion","volume":"88","author":"De Oliveira","year":"2016","journal-title":"Food Res Int"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1016\/j.foodchem.2017.07.145","article-title":"A first step towards a consensus static in vitro model for simulating full-term infant digestion","volume":"240","author":"M\u00e9nard","year":"2018","journal-title":"Food Chem"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1002\/mnfr.200900142","article-title":"Comparative resistance of food proteins to adult and infant in vitro digestion models","volume":"54","author":"Dupont","year":"2010","journal-title":"Mol Nutr Food Res"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1016\/j.foodres.2015.07.030","article-title":"Gastrointestinal digestion of dairy and soy proteins in infant formulas: an in vitro study","volume":"76","author":"Nguyen","year":"2015","journal-title":"Food Res Int"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"5819","DOI":"10.1002\/jsfa.9852","article-title":"Protein digestion properties of Xinong Saanen goat colostrum and mature milk using in vitro digestion model","volume":"99","author":"Sun","year":"2019","journal-title":"J Sci Food Agric"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"108210","DOI":"10.1016\/j.meatsci.2020.108210","article-title":"Increased protein digestibility of beef with aging in an infant in vitro digestion model","volume":"169","author":"Lee","year":"2020","journal-title":"Meat Sci"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"2102","DOI":"10.1039\/C8FO01940A","article-title":"Free fatty acid release from vegetable and bovine milk fat-based infant formulas and human milk during two-phase in vitro digestion","volume":"10","author":"Hageman","year":"2019","journal-title":"Food Funct"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1177\/1941406412452759","article-title":"Addition of calcium and phosphorus to preterm donor human milk and the impact on protein, fat, and calcium digestibility in vitro","volume":"4","author":"Fogleman","year":"2012","journal-title":"ICAN Infant Child Adolesc Nutr"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"e0189807","DOI":"10.1371\/journal.pone.0189807","article-title":"In vitro dynamic model simulating the digestive tract of 6-month-old infants","volume":"12","author":"Passannanti","year":"2017","journal-title":"PLoS One"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"362","DOI":"10.3390\/foods9030362","article-title":"Are Faba bean and pea proteins potential whey protein substitutes in infant formulas? An in vitro dynamic digestion approach","volume":"9","author":"Le Roux","year":"2020","journal-title":"Foods"},{"key":"ref22","first-page":"13","article-title":"The development of the small intestine","volume":"64","author":"Thomson","year":"1986","journal-title":"CJPP"},{"key":"ref23","doi-asserted-by":"crossref","DOI":"10.1177\/003591576105400922","volume-title":"Motility of the intestine","author":"B\u00fclbring","year":"1961"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1136\/adc.66.1_Spec_No.3","article-title":"Development of intestinal motility","volume":"66","author":"Bisset","year":"1991","journal-title":"Arch Dis Child"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.earlhumdev.2017.09.005","article-title":"Motility disorders in infants","volume":"114","author":"Koppen","year":"2017","journal-title":"Early Hum Dev"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1016\/S0022-3476(89)80302-6","article-title":"Gestational evolution of small intestine motility in preterm and term infants","volume":"115","author":"Berseth","year":"1989","journal-title":"J Pediatr"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1111\/j.1365-2982.1989.tb00152.x","article-title":"Postnatal maturation of small intestinal motility in preterm and term infants","volume":"1","author":"Amarnath","year":"1989","journal-title":"J Neurogastroenterol Motil"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"14","DOI":"10.3390\/nu14071405","article-title":"Development of the gastrointestinal tract in newborns as a challenge for an appropriate nutrition: a narrative review","volume":"14","author":"Indrio","year":"2022","journal-title":"Nutrients"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1321","DOI":"10.1136\/gut.32.11.1321","article-title":"Small intestinal length: a factor essential for gut adaptation","volume":"32","author":"Weaver","year":"1991","journal-title":"Gut"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1136\/gut.29.4.483","article-title":"Ontogeny of fasting small intestinal motor activity in the human infant","volume":"29","author":"Bisset","year":"1988","journal-title":"Gut"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1002\/j.1536-4801.2004.tb00870.x","article-title":"Gastric emptying and small intestinal transit time in preterm infants: a scintigraphic method","volume":"39","author":"Bod\u00e9","year":"2004","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1203\/00006450-197304000-00023","article-title":"The development of specific responses of the exocrine pancreas to Pancreozymin and secretin stimulation in newborn infants","volume":"7","author":"Zoppi","year":"1973","journal-title":"Pediatr Res"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1177\/026119299502300205","article-title":"A multicompartmental dynamic computer-controlled model simulating the stomach and small intestine","volume":"23","author":"Minekus","year":"1995","journal-title":"Altern Lab Anim"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"2105","DOI":"10.1017\/S000711451200027X","article-title":"In vivo digestion of infant formula in piglets: protein digestion kinetics and release of bioactive peptides","volume":"108","author":"Bouzerzour","year":"2012","journal-title":"Br J Nutr"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"e115221","DOI":"10.1590\/fst.115221","article-title":"Development of a reliable pH-STAT in-vitro model for gastrointestinal digestion of lipids and application for infant formula","volume":"42","author":"Wang","year":"2022","journal-title":"Food Sci Technol"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1053\/gast.2000.18140","article-title":"The specific activities of human digestive lipases measured from the in vivo and in vitro lipolysis of test meals","volume":"119","author":"Carri\u00e8re","year":"2000","journal-title":"Gastroenterology"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1146\/annurev.ph.32.030170.001035","article-title":"Digestion: intestinal secretion","volume":"32","author":"Hendrix","year":"1970","journal-title":"Annu Rev Physiol"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1016\/S0955-2863(02)00181-X","article-title":"Regulation mechanisms of intestinal secretion: implications in nutrient absorption","volume":"13","author":"Wapnir","year":"2002","journal-title":"J Nutr Biochem"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1038\/s41596-018-0119-1","article-title":"INFOGEST static in vitro simulation of gastrointestinal food digestion","volume":"14","author":"Brodkorb","year":"2019","journal-title":"Nat Protoc"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1079\/PNS2004376","article-title":"Fluid, electrolytes and nutrition: physiological and clinical aspects","volume":"63","author":"Lobo","year":"2004","journal-title":"Proc Nutr Soc"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1136\/adc.38.199.231","article-title":"Fluid and electrolyte requirements of newborn infants with intestinal obstruction","volume":"38","author":"Peonides","year":"1963","journal-title":"Arch Dis Child"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"12","DOI":"10.3390\/nu12082249","article-title":"Macronutrient intake from human Milk, infant growth, and body composition at term equivalent age: a longitudinal study of hospitalized very preterm infants","volume":"12","author":"Belfort","year":"2020","journal-title":"Nutrients"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"2007","DOI":"10.1194\/jlr.R200012-JLR200","article-title":"The triglyceride lipases of the pancreas","volume":"43","author":"Lowe","year":"2002","journal-title":"J Lipid Res"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"1427","DOI":"10.1080\/10408398.2011.640757","article-title":"Specificity of infant digestive conditions: some clues for developing relevant in vitro models","volume":"54","author":"Bourlieu","year":"2014","journal-title":"Crit Rev Food Sci Nutr"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"1876","DOI":"10.1002\/mnfr.201500883","article-title":"Infant digestion physiology and the relevance of in vitro biochemical models to test infant formula lipid digestion","volume":"60","author":"Poquet","year":"2016","journal-title":"Mol Nutr Food Res"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1159\/000244172","article-title":"Activities of trypsin and lipase in duodenal aspirates of healthy preterm infants: effects of gestational and postnatal age","volume":"67","author":"Boehm","year":"1995","journal-title":"Biol Neonate"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1203\/00006450-197212000-00005","article-title":"Exocrine pancreas function in premature and full term neonates","volume":"6","author":"Zoppi","year":"1972","journal-title":"Pediatr Res"},{"key":"ref48","first-page":"571","article-title":"Bile acids and pancreatic enzymes during absorption in the newborn","author":"Norman","year":"1972"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1016\/0005-2760(77)90197-7","article-title":"The action of bile salts and other detergents on pancreatic lipase and the interaction with colipase","volume":"488","author":"Borgstr\u00f6m","year":"1977","journal-title":"Biochimica et Biophysica Acta"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"16509","DOI":"10.1016\/S0021-9258(18)42032-7","article-title":"Two novel human pancreatic lipase related proteins, hPLRP1 and hPLRP2. Differences in colipase dependence and in lipase activity","volume":"267","author":"Giller","year":"1992","journal-title":"J Biol Chem"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1172\/jci110466","article-title":"Colipase and maximally activated pancreatic lipase in normal subjects and patients with steatorrhea","volume":"69","author":"Gaskin","year":"1982","journal-title":"J Clin Invest"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1203\/00006450-200012000-00006","article-title":"Parallel secretion of pancreatic phospholipase A2, phospholipase A1, lipase, and colipase in children with exocrine pancreatic dysfunction","volume":"48","author":"Nouri-Sorkhabi","year":"2000","journal-title":"Pediatr Res"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1080\/00365521.1975.12097016","article-title":"Lipase and co-lipase activities of human small intestinal contents after a liquid test meal","volume":"10","author":"Borgstr\u00f6m","year":"1975","journal-title":"Scand J Gastroenterol"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1016\/j.foodres.2018.01.003","article-title":"In vitro lipolysis of dairy and soy based infant formula","volume":"106","author":"Nguyen","year":"2018","journal-title":"Food Res Int"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"1702","DOI":"10.1039\/C9FO01293A","article-title":"A standardised semi-dynamic in vitro digestion method suitable for food\u2013an international consensus","volume":"11","author":"Mulet-Cabero","year":"2020","journal-title":"Food Funct"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"1949","DOI":"10.1194\/jlr.M015685","article-title":"BSSL and PLRP2: key enzymes for lipid digestion in the newborn examined using the Caco-2 cell line","volume":"52","author":"Andersson","year":"2011","journal-title":"J Lipid Res"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1203\/00006450-200002000-00006","article-title":"Discoordinate expression of pancreatic lipase and two related proteins in the human fetal pancreas","volume":"47","author":"Yang","year":"2000","journal-title":"Pediatr Res"},{"key":"ref58","doi-asserted-by":"publisher","first-page":"G914","DOI":"10.1152\/ajpgi.1994.266.5.G914","article-title":"Rat pancreatic lipase and two related proteins: enzymatic properties and mRNA expression during development","volume":"266","author":"Payne","year":"1994","journal-title":"Am J Phys"},{"key":"ref59","doi-asserted-by":"publisher","first-page":"31215","DOI":"10.1074\/jbc.273.47.31215","article-title":"Decreased neonatal dietary fat absorption and T cell cytotoxicity in pancreatic lipase-related protein 2-deficient mice","volume":"273","author":"Lowe","year":"1998","journal-title":"J Biol Chem"},{"key":"ref60","doi-asserted-by":"publisher","first-page":"1592","DOI":"10.1002\/mnfr.200800563","article-title":"Individual and combined action of pancreatic lipase and pancreatic lipase-related proteins 1 and 2 on native versus homogenized milk fat globules","volume":"53","author":"Berton","year":"2009","journal-title":"Mol Nutr Food Res"},{"key":"ref61","doi-asserted-by":"publisher","first-page":"S56","DOI":"10.1016\/S0022-3476(06)80737-7","article-title":"Human milk bile salt-stimulated lipase: functional and molecular aspects","volume":"125","author":"Hernell","year":"1994","journal-title":"J Pediatr"},{"key":"ref62","doi-asserted-by":"publisher","first-page":"1221","DOI":"10.1172\/JCI114556","article-title":"The complete digestion of human milk triacylglycerol in vitro requires gastric lipase, pancreatic colipase-dependent lipase, and bile salt-stimulated lipase","volume":"85","author":"Bernb\u00e4ck","year":"1990","journal-title":"J Clin Invest"},{"key":"ref63","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/0167-4781(95)00141-3","article-title":"Bile salt-dependent lipase transcripts in human fetal tissues","volume":"1264","author":"Roudani","year":"1995","journal-title":"Biochimica et Biophysica Acta"},{"key":"ref64","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1097\/00005176-198707000-00019","article-title":"Bile salt-stimulated lipase of human milk: characteristics of the enzyme in the milk of mothers of premature and full-term infants","volume":"6","author":"Freed","year":"1987","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"ref65","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1203\/PDR.0b013e3181559e75","article-title":"Bile salt\u2013stimulated lipase and pancreatic lipase-related protein 2 are the dominating lipases in neonatal fat digestion in mice and rats","volume":"62","author":"Li","year":"2007","journal-title":"Pediatr Res"},{"key":"ref66","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/jpc.12104","article-title":"Bioactive proteins in breast milk","volume":"49","author":"L\u00f6nnerdal","year":"2013","journal-title":"J Paediatr Child Health"},{"key":"ref67","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1007\/s00535-006-1874-2","article-title":"The role of trypsin, trypsin inhibitor, and trypsin receptor in the onset and aggravation of pancreatitis","volume":"41","author":"Hirota","year":"2006","journal-title":"J Gastroenterol"},{"key":"ref68","doi-asserted-by":"publisher","first-page":"1240","DOI":"10.1203\/00006450-198109000-00003","article-title":"The development of pancreatic function in premature infants after milk-based and soy-based formulas","volume":"15","author":"Lebenthal","year":"1981","journal-title":"Pediatr Res"},{"key":"ref69","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1542\/peds.66.4.556","article-title":"Development of functional response in human exocrine pancreas","volume":"66","author":"Lebenthal","year":"1980","journal-title":"Pediatrics"},{"key":"ref70","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1111\/j.1651-2227.1974.tb04867.x","article-title":"Proteolytic activity in duodenal juice in infants, children, and adults","volume":"63","author":"Lindberg","year":"1974","journal-title":"Acta Paediatr"},{"key":"ref71","first-page":"454","article-title":"Digestive studies in children. Studies under normal and pathological conditions","volume-title":"Am J Dis Child","author":"Borgstr\u00f6m","year":"1961"},{"key":"ref72","first-page":"338","article-title":"Enzyme concentration and absorption of protein and glucose in duodenum of premature infants","volume":"99","author":"Borgstr\u00f6m","year":"1960","journal-title":"AMA Am J Dis Child"},{"key":"ref73","doi-asserted-by":"publisher","first-page":"134720","DOI":"10.1016\/j.foodchem.2022.134720","article-title":"In vitro digestibility of dietary proteins and in vitro DIAAS analytical workflow based on the INFOGEST static protocol and its validation with in vivo data","volume":"404","author":"Sousa","year":"2023","journal-title":"Food Chem"},{"key":"ref74","doi-asserted-by":"publisher","first-page":"1677","DOI":"10.1002\/mnfr.200900582","article-title":"Food processing increases casein resistance to simulated infant digestion","volume":"54","author":"Dupont","year":"2010","journal-title":"Mol Nutr Food Res"},{"key":"ref75","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1038\/ejcn.2015.162","article-title":"Breast milk composition and infant nutrient intakes during the first 12 months of life","volume":"70","author":"Grote","year":"2016","journal-title":"Eur J Clin Nutr"},{"key":"ref76","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1016\/B978-0-12-395630-9.50145-6","volume-title":"Methods of Enzymatic Analysis","author":"Wirnt","year":"1965"},{"key":"ref77","doi-asserted-by":"publisher","first-page":"7225","DOI":"10.1021\/jf405601e","article-title":"Predicting the important enzymes in human breast milk digestion","volume":"62","author":"Khaldi","year":"2014","journal-title":"J Agric Food Chem"},{"key":"ref78","first-page":"466","article-title":"Trypsin and elastase activity in duodenal juice from preterm infants before and after a meal of human milk","volume":"4","author":"Engberg","year":"1999","journal-title":"PNM"},{"key":"ref79","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1097\/00005792-197607000-00001","article-title":"Amylase\u2014its clinical significance: a review of the literature","volume":"55","author":"Salt","year":"1976","journal-title":"Medicine (Baltimore)"},{"key":"ref80","doi-asserted-by":"publisher","first-page":"1299","DOI":"10.1016\/s0016-5085(77)80031-0","article-title":"Developmental pattern of small intestinal enterokinase and disaccharidase activities in the human fetus","volume":"72","author":"Antonowicz","year":"1977","journal-title":"Gastroenterology"},{"key":"ref81","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1136\/gut.25.9.925","article-title":"Early organogenesis of human small intestine: scanning electron microscopy and brush border enzymology","volume":"25","author":"Lacroix","year":"1984","journal-title":"Gut"},{"key":"ref82","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1093\/ajcn.81.2.472","article-title":"<article-title update=\"added\">influence of changes in lactase activity and small-intestinal mucosal growth on lactose digestion and absorption in preterm infants","volume":"81","author":"Shulman","year":"2005","journal-title":"Am J Clin Nutr"},{"key":"ref83","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1136\/adc.61.9.896","article-title":"Neonatal intestinal lactase activity","volume":"61","author":"Weaver","year":"1986","journal-title":"Arch Dis Child"},{"key":"ref84","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.1136\/gut.27.11.1357","article-title":"Postnatal development of disaccharidase activities in jejunal fluid of preterm neonates","volume":"27","author":"Mayne","year":"1986","journal-title":"Gut"},{"key":"ref85","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1136\/adc.58.9.686","article-title":"Disaccharidase activities in jejunal fluid","volume":"58","author":"Aramayo","year":"1983","journal-title":"Arch Dis Child"},{"key":"ref86","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1136\/bmj.1.5539.527","article-title":"Lactase activity in newborn and infant Baganda","volume":"1","author":"Cook","year":"1967","journal-title":"Br Med J"},{"key":"ref87","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1002\/9780470720240.ch11","volume-title":"Ciba Foundation Symposium 42-Acute Diarrhoea in Childhood","author":"Torres-Pinedo","year":"1976"},{"key":"ref88","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1515\/hsz-2015-0109","article-title":"Secretory sphingomyelinase in health and disease","volume":"396","author":"Kornhuber","year":"2015","journal-title":"Biol Chem"},{"key":"ref89","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.bbalip.2006.03.007","article-title":"Alkaline sphingomyelinase: an old enzyme with novel implications","volume":"1761","author":"Duan","year":"2006","journal-title":"Biochim Biophys Acta Mol Cell Biol"},{"key":"ref90","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1203\/01.pdr.0000250534.92934.c2","article-title":"Human meconium contains significant amounts of alkaline sphingomyelinase, neutral ceramidase, and sphingolipid metabolites","volume":"61","author":"Duan","year":"2007","journal-title":"Pediatr Res"},{"key":"ref91","first-page":"1801","article-title":"Distribution of alkaline sphingomyelinase activity in human beings and animals: tissue and species differences","volume-title":"Dig Dis Sci","author":"Duan","year":"1996"},{"key":"ref92","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1042\/bj0890057","article-title":"The function of bile salts in fat absorption. The solvent properties of dilute micellar solutions of conjugated bile salts","volume":"89","author":"Hofmann","year":"1963","journal-title":"Biochem J"},{"key":"ref93","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1136\/adc.49.3.174","article-title":"Role of bile salts in fat malabsorption of premature infants","volume":"49","author":"Signer","year":"1974","journal-title":"Arch Dis Child"},{"key":"ref94","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1136\/adc.50.11.837","article-title":"Duodenal bile acids in infancy","volume":"50","author":"Challacombe","year":"1975","journal-title":"Arch Dis Child"},{"key":"ref95","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1007\/BF02939169","article-title":"A comprehensive study of duodenal bile salts in newborn infants and their relationship to fat absorption","volume":"149","author":"Glasgow","year":"1980","journal-title":"Ir J Med Sci"},{"key":"ref96","doi-asserted-by":"publisher","first-page":"838","DOI":"10.1172\/jci110101","article-title":"Fat digestion in the newborn. Characterization of lipase in gastric aspirates of premature and term infants","volume":"67","author":"Hamosh","year":"1981","journal-title":"J Clin Invest"},{"key":"ref97","doi-asserted-by":"publisher","first-page":"1162","DOI":"10.1208\/s12248-014-9652-1","article-title":"Similarities and differences in gastrointestinal physiology between neonates and adults: a physiologically based pharmacokinetic modeling perspective","volume":"16","author":"Yu","year":"2014","journal-title":"AAPS J"},{"key":"ref98","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.ejpb.2020.11.010","article-title":"Characterisation of fasted state gastric and intestinal fluids collected from children","volume":"158","author":"Pawar","year":"2021","journal-title":"Eur J Pharm Biopharm"},{"key":"ref99","doi-asserted-by":"publisher","first-page":"122943","DOI":"10.1016\/j.ijpharm.2023.122943","article-title":"Characterization of neonatal and infant enterostomy fluids","volume":"639","author":"de Waal","year":"2023","journal-title":"Int J Pharm"},{"key":"ref100","doi-asserted-by":"publisher","first-page":"2962","DOI":"10.1097\/00003246-200008000-00046","article-title":"Indicators of postpyloric feeding tube placement in children","volume":"28","author":"Gharpure","year":"2000","journal-title":"Crit Care Med"},{"key":"ref101","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1542\/peds.98.2.242","article-title":"Rapid placement of transpyloric feeding tubes: a comparison of pH-assisted and standard insertion techniques in children","volume":"98","author":"Krafte-Jacobs","year":"1996","journal-title":"Pediatrics"},{"key":"ref102","first-page":"152","article-title":"Investigations on the bacterial flora, pH, and sugar content in the intestinal tract of infants","volume-title":"J Pediatr","author":"Barbero","year":"1952"},{"key":"ref103","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1111\/j.1432-1033.1973.tb02957.x","article-title":"Pancreatic lipase and co-lipase","volume":"37","author":"Borgstr\u00f6m","year":"1973","journal-title":"Eur J Biochem"},{"key":"ref104","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/S0955-2863(03)00008-1","article-title":"Pancreatic lipase activity as influenced by unconjugated bile acids and pH, measured in vitro and in vivo","volume":"14","author":"Knarreborg","year":"2003","journal-title":"J Nutr Biochem"},{"key":"ref105","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/B978-0-12-091302-2.50099-2","volume-title":"Methods of Enzymatic Analysis","author":"Rick","year":"1974"},{"key":"ref106","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.bpg.2016.02.007","article-title":"Physiology of intestinal absorption and secretion","volume":"30","author":"Kiela","year":"2016","journal-title":"Best Pract Res Clin Gastroenterol"},{"key":"ref107","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0022-3476(83)80276-5","article-title":"Impact of development of the gastrointestinal tract on infant feeding","volume":"102","author":"Lebenthal","year":"1983","journal-title":"J Pediatr"},{"key":"ref108","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1111\/j.1651-2227.1989.tb17932.x","article-title":"Macromolecular absorption in preterm and term infants","volume":"78","author":"Axelsson","year":"1989","journal-title":"Acta Paediatr"},{"key":"ref109","doi-asserted-by":"publisher","first-page":"250703472","DOI":"10.48550\/arXiv.2507.03472","article-title":"Intestinal villi and crypts density maximizing nutrient absorption","author":"Garic","year":"2025","journal-title":"ar Xiv preprint ar Xiv"},{"key":"ref110","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1002\/ar.1091950307","article-title":"Development of villus absorptive cells in the human fetal small intestine: a morphological and morphometric study","volume":"195","author":"Moxey","year":"1979","journal-title":"Anat Rec"},{"key":"ref111","first-page":"161","article-title":"Growth and morphological changes in the small and the large intestine in piglets during the first three days after birth","volume":"18","author":"Xu","year":"1992","journal-title":"J Dev Physiol"},{"key":"ref112","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/j.cofs.2021.04.002","article-title":"Intestinal cell models for investigating the uptake, metabolism and absorption of dietary nutrients and bioactive compounds","volume":"41","author":"Rodrigues","year":"2021","journal-title":"Curr Opin Food Sci"},{"key":"ref113","doi-asserted-by":"publisher","first-page":"19265","DOI":"10.1021\/acs.jafc.3c05479","article-title":"A shared perspective on in vitro and in vivo models to assay intestinal Transepithelial transport of food compounds","volume":"71","author":"Hevia","year":"2023","journal-title":"J Agric Food Chem"},{"key":"ref114","doi-asserted-by":"publisher","first-page":"3480","DOI":"10.1021\/jf010106t","article-title":"Calcium, iron, and zinc uptake from digests of infant formulas by Caco-2 cells","volume":"49","author":"Jovan\u00ed","year":"2001","journal-title":"J Agric Food Chem"},{"key":"ref115","doi-asserted-by":"publisher","first-page":"3635","DOI":"10.1007\/s00018-011-0822-3","article-title":"Composition and functional role of the mucus layers in the intestine","volume":"68","author":"Johansson","year":"2011","journal-title":"Cell Mol Life Sci"},{"key":"ref116","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1136\/gut.43.4.519","article-title":"Mucin gene expression in human embryonic and fetal intestine","volume":"43","author":"Buisine","year":"1998","journal-title":"Gut"},{"key":"ref117","first-page":"561","article-title":"Mucin histochemistry of the digestive tract in the human fetus","volume":"14","author":"Stauffer","year":"1990","journal-title":"Gastroenterol Clin Biol"},{"key":"ref118","doi-asserted-by":"publisher","first-page":"1473","DOI":"10.1007\/s10620-016-4032-6","article-title":"Mucin\u2013microbiota interaction during postnatal maturation of the intestinal ecosystem: clinical implications","volume":"61","author":"Rokhsefat","year":"2016","journal-title":"Dig Dis Sci"},{"key":"ref119","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1042\/bj2150405","article-title":"Age-related changes in chemical composition and physical properties of mucus glycoproteins from rat small intestine","volume":"215","author":"Shub","year":"1983","journal-title":"Biochem J"},{"key":"ref120","doi-asserted-by":"publisher","first-page":"e95274","DOI":"10.1371\/journal.pone.0095274","article-title":"Transport of particles in intestinal mucus under simulated infant and adult physiological conditions: impact of mucus structure and extracellular DNA","volume":"9","author":"Macierzanka","year":"2014","journal-title":"PLoS One"},{"key":"ref121","doi-asserted-by":"publisher","first-page":"5893","DOI":"10.1002\/jsfa.12692","article-title":"Comparative evaluation of static and dynamic simulated digestion models","volume":"103","author":"Wang","year":"2023","journal-title":"J Sci Food Agric"},{"key":"ref122","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1001\/archpedi.1930.01940060055005","article-title":"The gastric and duodenal contents of normal infants and children: the duodenal enzyme activity and the gastric and duodenal reactions (H-ion)","volume":"40","author":"Klumpp","year":"1930","journal-title":"Am J Dis Child"},{"key":"ref123","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1203\/00006450-197805000-00004","article-title":"Decrease of lipase and esterase activities in intestinal contents of newborn infants during test meals","volume":"12","author":"Fredrikzon","year":"1978","journal-title":"Pediatr Res"}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2026.1826318\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T04:49:31Z","timestamp":1782276571000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2026.1826318\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,24]]},"references-count":123,"alternative-id":["10.3389\/fnut.2026.1826318"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2026.1826318","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,24]]},"article-number":"1826318"}}