{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T22:23:59Z","timestamp":1790115839882,"version":"4.0.1"},"reference-count":52,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,6,21]],"date-time":"2023-06-21T00:00:00Z","timestamp":1687305600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Essential amino acids (AAs) play a key role in stimulating intestinal adaptation after massive small gut resection. The nutritional effect of dietary amino acids during intestinal regrowth has received considerable attention in recent years. This review explores the significance of dietary amino acids in the nutritional management of infants and children with intestinal failure and short bowel syndrome (SBS) as reported in the medical literature over the last three decades. A literature search was conducted using electronic databases. Breast milk emerged as the first-line enteral regimen recommended for infants with SBS. Hydrolyzed formulas (HFs) or amino acid formulas (AAFs) are recommended when breast milk is not available or if the infant cannot tolerate whole protein milk. The superiority of AAFs over HFs has never been demonstrated. Although glutamine (GLN) is the main fuel for enterocytes, GLN supplementation in infants with SBS showed no difference in the child\u2019s dependence upon parenteral nutrition (PN). Circulating citrulline is considered a major determinant of survival and nutritional prognosis of SBS patients. Early enteral nutrition and dietary supplementation of AAs following bowel resection in children are essential for the development of intestinal adaptation, thereby eliminating the need for PN.<\/jats:p>","DOI":"10.3390\/nu15132826","type":"journal-article","created":{"date-parts":[[2023,6,22]],"date-time":"2023-06-22T02:09:17Z","timestamp":1687399757000},"page":"2826","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Impact of Dietary Protein on the Management of Pediatric Short Bowel Syndrome"],"prefix":"10.3390","volume":"15","author":[{"given":"Igor","family":"Sukhotnik","sequence":"first","affiliation":[{"name":"Department of Pediatric Surgery, Dana-Dwek Children\u2019s Hospital, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, 6 Weizmann St., Tel Aviv 6423906, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reut","family":"Levi","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology, Dana-Dwek Children\u2019s Hospital, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, 6 Weizmann St., Tel Aviv 6423906, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadar","family":"Moran-Lev","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology, Dana-Dwek Children\u2019s Hospital, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, 6 Weizmann St., Tel Aviv 6423906, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1002\/jpen.2232","article-title":"ASPEN definitions in pediatric intestinal failure","volume":"46","author":"Modi","year":"2022","journal-title":"J. Parenter. Enter. Nutr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1056\/NEJMra1602650","article-title":"Pediatric intestinal failure","volume":"377","author":"Duggan","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1016\/j.jpedsurg.2006.12.033","article-title":"Group for the Improvement of Intestinal Function and Treatment. Neonatal short bowel syndrome outcomes after the establishment of the first Canadian multidisciplinary intestinal rehabilitation program: Preliminary experience","volume":"42","author":"Diamond","year":"2007","journal-title":"J. Pediatr. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.clp.2022.02.016","article-title":"Nutritional management of short bowel syndrome","volume":"49","author":"Premkumar","year":"2022","journal-title":"Clin. Perinatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.clp.2016.11.013","article-title":"Bioactive proteins in human milk-potential benefits for preterm infants","volume":"44","author":"Lonnerdal","year":"2017","journal-title":"Clin. Perinatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.jpedsurg.2023.01.011","article-title":"Current short bowel syndrome management: An era of improved outcomes and continued challenges","volume":"58","author":"Jaksic","year":"2023","journal-title":"J. Pediatr. Surg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/S0889-8553(05)70014-5","article-title":"Short bowel syndrome","volume":"27","author":"Scolapio","year":"1998","journal-title":"Gastroenterol. Clin. North Am."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.bpg.2016.03.009","article-title":"Enteral approaches in malabsorption","volume":"30","author":"Avitzur","year":"2016","journal-title":"Best Pract. Res. Clin. Gastroenterol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1046\/j.1440-1746.2002.02872.x","article-title":"Influence of diet complexity on intestinal adaptation following massive small bowel resection in a preclinical model","volume":"17","author":"Bines","year":"2002","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1186\/s40792-022-01527-1","article-title":"A rare case of eosinophilic gastrointestinal disorders with short bowel syndrome after strangulated bowel obstruction","volume":"14","author":"Arai","year":"2022","journal-title":"Surg. Case Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.clnu.2012.09.007","article-title":"Neonatal short bowel syndrome as a model of intestinal failure: Physiological background for enteral feeding","volume":"32","author":"Goulet","year":"2013","journal-title":"Clin. Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1097\/00005176-199802000-00001","article-title":"Reducing parenteral requirement in children with short bowel syndrome: Impact of an amino acid-based complete infant formula","volume":"26","author":"Bines","year":"1998","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1097\/00005176-200211000-00005","article-title":"Hydrolyzed versus nonhydrolyzed protein diet in short bowel syndrome in children","volume":"35","author":"Ksiazyk","year":"2002","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1038\/jp.2015.105","article-title":"Implementation of feeding guidelines in infants at risk of intestinal failure","volume":"35","author":"Shores","year":"2015","journal-title":"J. Perinatol."},{"key":"ref_15","first-page":"297575","article-title":"The influence of neocate in paediatric short bowel syndrome on PN weaning","volume":"2010","author":"Mahler","year":"2010","journal-title":"J. Nutr. Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1067\/mpd.2001.114481","article-title":"Nutritional and other postoperative management of neonates with short bowel syndrome correlates with clinical outcomes","volume":"139","author":"Andorsky","year":"2001","journal-title":"J. Pediatr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2315","DOI":"10.1016\/j.clnu.2018.06.945","article-title":"ESPGHAN\/ESPEN\/ESPR\/CSPEN working group on pediatric parenteral nutrition. ESPGHAN\/ESPEN\/ESPR\/CSPEN guidelines on pediatric parenteral nutrition: Amino acids","volume":"37","author":"Carnielli","year":"2018","journal-title":"Clin. Nutr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1080\/17474124.2017.1335196","article-title":"Enteral nutrition in pediatric intestinal failure: Does initial feeding impact on intestinal adaptation?","volume":"11","author":"Capriati","year":"2017","journal-title":"Expert Rev. Gastroenterol. Hepatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1177\/0884533616661011","article-title":"Transition to a tube feeding formula with real food ingredients in pediatric patients with intestinal failure","volume":"32","author":"Samela","year":"2017","journal-title":"Nutr. Clin. Pract."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1002\/ncp.10866","article-title":"Blenderized enteral nutrition in pediatric short gut syndrome: Tolerance and clinical outcomes","volume":"37","author":"Zong","year":"2022","journal-title":"Nutr. Clin. Pract."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"S27","DOI":"10.1002\/ncp.10991","article-title":"Anatomical and physiological considerations in short bowel syndrome: Emphasis on intestinal adaptation and the role of enterohormones","volume":"38","author":"Tappenden","year":"2023","journal-title":"Nutr. Clin. Pract."},{"key":"ref_22","first-page":"299","article-title":"Short Bowel Syndrome: A Paradigm for Intestinal Adaptation to Nutrition?","volume":"23","author":"Billiauws","year":"2020","journal-title":"Annu. Rev. Nutr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.gtc.2019.08.004","article-title":"Predictors of Intestinal Adaptation in Children","volume":"48","author":"Venick","year":"2019","journal-title":"Gastroenterol. Clin."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1053\/j.gastro.2005.11.051","article-title":"Mechanisms of enteral nutrient-enhanced intestinal adaptation","volume":"130","author":"Tappenden","year":"2006","journal-title":"Gastroenterology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1007\/s003830100695","article-title":"Intestinal adaptation in short-bowel syndrome in infants and children: A collective review","volume":"18","author":"Sukhotnik","year":"2002","journal-title":"Pediatr. Surg. Int."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2727","DOI":"10.1017\/S1751731119001800","article-title":"Review: The roles and functions of glutamine on intestinal health and performance of weaning pigs","volume":"13","author":"Ji","year":"2019","journal-title":"Animal"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Kim, M.H., and Kim, H. (2017). The roles of glutamine in the intestine and its implication in intestinal diseases. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18051051"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1136\/gut.41.4.487","article-title":"Prophylactic effect of dietary glutamine supplementation on interleukin 8 and tumour necrosis factor \u03b1 production in trinitrobenzene sulphonic acid induced colitis","volume":"41","author":"Ameho","year":"1997","journal-title":"Gut"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Anderson, P.M., and Lalla, R.V. (2020). Glutamine for amelioration of radiation and chemotherapy associated mucositis during cancer therapy. Nutrients, 12.","DOI":"10.3390\/nu12061675"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"175480","DOI":"10.1016\/j.ejphar.2022.175480","article-title":"Glutamine alleviates intestinal injury in a murine burn sepsis model by maintaining intestinal intraepithelial lymphocyte homeostasis","volume":"940","author":"Chen","year":"2023","journal-title":"Eur. J. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"463","DOI":"10.4318\/tjg.2013.0555","article-title":"Effect of growth hormone, glutamine, and enteral nutrition on intestinal adaptation in patients with short bowel syndrome","volume":"24","author":"Guo","year":"2013","journal-title":"Turk. J. Gastroenterol."},{"key":"ref_32","first-page":"CD006321","article-title":"Human growth hormone and glutamine for patients with short bowel syndrome","volume":"16","author":"Wales","year":"2010","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1097\/01.sla.0000186479.53295.14","article-title":"Growth hormone, glutamine, and an optimal diet reduces parenteral nutrition in patients with short bowel syndrome: A prospective, randomized, placebo-controlled, double-blind clinical trial","volume":"242","author":"Byrne","year":"2005","journal-title":"Ann. Surg."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"45S","DOI":"10.1177\/0148607114526241","article-title":"Pharmacologic options for intestinal rehabilitation in patients with short bowel syndrome","volume":"38","author":"Jeppese","year":"2014","journal-title":"J. Parenter. Enter. Nutr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.1007\/s00726-014-1825-9","article-title":"L-Arginine and its metabolites in kidney and cardiovascular disease","volume":"46","author":"Popolo","year":"2014","journal-title":"Amino Acids"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1016\/j.niox.2017.12.009","article-title":"A pilot study of a non-invasive oral nitrate stable isotopic method suggests that arginine and citrulline supplementation increases whole-body no production in Tanzanian children with sickle cell disease","volume":"74","author":"Marealle","year":"2018","journal-title":"Nitric Oxide"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1038\/s41390-020-01139-1","article-title":"Intestinal resection affects whole-body arginine synthesis in neonatal piglets","volume":"89","author":"Lansing","year":"2021","journal-title":"Pediatr. Res."},{"key":"ref_38","first-page":"554","article-title":"Effects of continuous enteral L-arginine in a rat model of the short bowel syndrome","volume":"16","author":"Jiang","year":"2007","journal-title":"Asia Pac. J. Clin. Nutr."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1016\/j.clnu.2017.10.009","article-title":"Citrulline in health and disease. Review on human studies","volume":"37","author":"Papadia","year":"2018","journal-title":"Clin. Nutr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1016\/S0016-5085(03)00170-7","article-title":"Plasma citrulline: A marker of enterocyte mass in villous atrophy-associated small bowel disease","volume":"124","author":"Crenn","year":"2003","journal-title":"Gastroenterology"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Maric, S., Restin, T., Muff, J.L., Camargo, S.M., Guglielmetti, L.C., Holland-Cunz, S.G., Crenn, P., and Vuille-Dit-Bille, R.N. (2021). Citrulline, biomarker of enterocyte functional mass and dietary supplement. Metabolism, transport, and current evidence for clinical use. Nutrients, 13.","DOI":"10.3390\/nu13082794"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.dld.2003.09.015","article-title":"Survival rate and prognostic factors in patients with intestinal failure","volume":"36","author":"Vantini","year":"2004","journal-title":"Dig. Liver Dis."},{"key":"ref_43","first-page":"e93","article-title":"Effect of Teduglutide, a Glucagon-like Peptide 2 Analog, on Citrulline Levels in Patients With Short Bowel Syndrome in Two Phase III Randomized Trials. Clin. Transl","volume":"6","author":"Seidner","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1017\/S0007114507841110","article-title":"Dose-ranging effects of citrulline administration on plasma amino acids and hormonal patterns in healthy subjects: The Citrudose pharmacokinetic study","volume":"99","author":"Moinard","year":"2007","journal-title":"Br. J. Nutr."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e147","DOI":"10.1016\/S2352-3026(18)30020-6","article-title":"Ready-to-Use Food Supplement, with or without Arginine and Citrulline, with Daily Chloroquine in Tanzanian Children with Sickle-Cell Disease: A Double-Blind, Random Order Crossover Trial","volume":"5","author":"Cox","year":"2018","journal-title":"Lancet Haematol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/1750-1172-7-32","article-title":"Suggested guidelines for the diagnosis and management of urea cycle disorders","volume":"7","author":"Boddaert","year":"2012","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"111118","DOI":"10.1016\/j.nut.2020.111118","article-title":"Dose-dependent beneficial effects of citrulline supplementation in short bowel syndrome in rats","volume":"85","author":"Filippi","year":"2021","journal-title":"Nutrition"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2599","DOI":"10.1016\/j.clnu.2018.12.030","article-title":"Effect of oral citrulline supplementation on whole body protein metabolism in adult patients with short bowel syndrome: A randomized, double- blind, cross-over study","volume":"38","author":"Jirka","year":"2019","journal-title":"Clin. Nutr."},{"key":"ref_49","first-page":"119","article-title":"Complementary feeding: A position paper by the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) Committee on Nutrition","volume":"64","author":"Fewtrell","year":"2017","journal-title":"JPGN"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1111\/j.1572-0241.2004.40836.x","article-title":"Intestinal rehabilitation and the short bowel syndrome: Part 2","volume":"99","author":"DiBaise","year":"2004","journal-title":"Am. J. Gastroenterol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Puoti, M.G., and K\u00f6glmeier, J. (2023). Nutritional management of intestinal failure due to short bowel syndrome in children. Nutrients, 15.","DOI":"10.3390\/nu15010062"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"617597","DOI":"10.1155\/2011\/617597","article-title":"Glutamine supplementation in sick children: Is it beneficial?","volume":"2011","author":"Mok","year":"2011","journal-title":"J. Nutr. Metab."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/13\/2826\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:57:52Z","timestamp":1760126272000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/13\/2826"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,21]]},"references-count":52,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["nu15132826"],"URL":"https:\/\/doi.org\/10.3390\/nu15132826","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,21]]}}}