Feng Haixia,Wang Ying.Effects of glucagon-like peptide 2 analogue on intestinal adaptation in pediatric short bowel syndrome[J].Journal of Clinical Pediatric Surgery,2025,(12):1117-1121.[doi:10.3760/cma.j.cn101785-202509037-005]
胰高血糖素样肽-2类似物在小儿短肠综合征治疗中的作用及应用
- Title:
- Effects of glucagon-like peptide 2 analogue on intestinal adaptation in pediatric short bowel syndrome
- 关键词:
- 胰高血糖素样肽-2类似物; 替度格鲁肽; 短肠综合征; 儿童
- Keywords:
- Glucagon-Like Peptide-2; Synthetic; Teduglutide; Short Bowel Syndrome; Child
- 摘要:
- 短肠综合征(short bowel syndrome,SBS)是导致儿童肠衰竭的主要原因,是由于残留的肠功能无法维持机体营养物质、液体、电解质或微量营养素稳态,因而需要长期依赖肠外营养(parenteral nutrition,PN)支持。肠康复治疗是SBS管理的核心策略,旨在促进肠道适应性代偿,恢复肠道自主功能,让患者最终摆脱PN。替度格鲁肽(teduglutide,TED)是全球首个且唯一获批用于治疗SBS的人胰高血糖素样肽-2(glucagon-like peptide-2,GLP-2)类似物,可通过促进肠黏膜增生,增加绒毛高度和隐窝深度,有效增强小肠的吸收功能,减少对于PN的需求,现已成为SBS的一线治疗药物。2024年2月,TED在中国正式获批用于成人及1岁以上儿童SBS患者,此举显著推动了我国SBS肠康复的临床进程。
- Abstract:
- Short bowel syndrome (SBS) is a major cause of intestinal failure (IF) in children.It occurs when residual intestinal function fails to maintain a proper homeostasis of nutrients,fluids,electrolytes or micronutrients.As a result,long-term parenteral nutrition (PN) is often required.The overall goal of SBS intestinal rehabilitation treatment is to promote intestinal adaptation and achieve intestinal autonomy.Teduglutide (TED) is the first developed and marketed (glucagon-like peptide-2,GLP-2) analogue for SBS.Through boosting villus height and crypt depth,it enhances the absorption function of small intestine and lowers PN dependence,making it a first-line therapeutic agent for SBS.In February 2024,TED was approved in China for treating SBS adults and children aged over 1 year.It is capable of accelerating the process of intestinal rehabilitation.
参考文献/References:
[1] Mangalat N,Teckman J.Pediatric intestinal failure review[J].Children (Basel),2018,5(7):100.DOI:10.3390/children5070100.
[2] 中华医学会肠外肠内营养学分会儿科学组,儿童短肠综合征诊断治疗专家共识工作组.儿童短肠综合征诊断治疗专家共识(2023版)[J].中国循证儿科杂志,2024,19(3):161-172.DOI:10.3969/j.issn.1673-5501.2024.03.001. Group of Pediatrics,Chinese Society for Parenteral and Enteral Nutrition,Expert Consensus Working Group on Diagnosing and Treating Short Bowel Syndrome in Children.Expert Consensus on Diagnosing and Treating Short Bowel Syndrome in Children (Edition 2023)[J].Chin J Evid Based Pediatr,2024,19(3):161-172.DOI:10.3969/j.issn.1673-5501.2024.03.001.
[3] Muto M,Kaji T,Onishi S,et al.An overview of the current management of short-bowel syndrome in pediatric patients[J].Surg Today,2022,52(1):12-21.DOI:10.1007/s00595-020-02207-z.
[4] Silva R,Guerra P,Rocha A,et al.Clinical,economic,and humanistic impact of short-bowel syndrome/chronic intestinal failure in Portugal (PARENTERAL Study)[J].GE Port J Gastroenterol,2022,30(4):293-304.DOI:10.1159/000526059.
[5] Puoti MG,D’Eusebio C,Littlechild H,et al.Risk factors for catheter-related bloodstream infections associated with home parental nutrition in children with intestinal failure:a prospective cohort study[J].Clin Nutr,2023,42(11):2241-2248.DOI:10.1016/j.clnu.2023.09.007.
[6] Stanciu S,De Silva A.Metabolic acidosis in short bowel syndrome:think D-lactic acid acidosis[J].BMJ Case Rep,2018,2018:bcr-2018-224221.DOI:10.1136/bcr-2018-224221.
[7] Pederiva F,Khalil B,Morabito A,et al.Impact of short bowel syndrome on quality of life and family:the patient’s perspective[J].Eur J Pediatr Surg,2019,29(2):196-202.DOI:10.1055/s-0037-1621737.
[8] Olieman J,Kastelijn W.Nutritional feeding strategies in pediatric intestinal failure[J].Nutrients,2020,12(1):177.DOI:10.3390/nu12010177.
[9] Goulet O,Baglin-Gobet S,Talbotec C,et al.Outcome and long-term growth after extensive small bowel resection in the neonatal period:a survey of 87 children[J].Eur J Pediatr Surg,2005,15(2):95-101.DOI:10.1055/s-2004-821214.
[10] Fatemizadeh R,Gollins L,Hagan J,et al.In neonatal-onset surgical short bowel syndrome survival is high,and enteral autonomy is related to residual bowel length[J].JPEN J Parenter Enteral Nutr,2022,46(2):339-347.DOI:10.1002/jpen.2124.
[11] Zhang T,Feng HX,Cao Y,et al.Long-term outcomes of various pediatric short bowel syndrome in China[J].Pediatr Surg Int,2021,37(4):495-502.DOI:10.1007/s00383-020-04797-8.
[12] Stanger JD,Oliveira C,Blackmore C,et al.The impact of multi-disciplinary intestinal rehabilitation programs on the outcome of pediatric patients with intestinal failure:a systematic review and meta-analysis[J].J Pediatr Surg,2013,48(5):983-992.DOI:10.1016/j.jpedsurg.2013.02.070.
[13] Tecos ME,Steinberger AE,Guo J,et al.Distal small bowel resection yields enhanced intestinal and colonic adaptation[J].J Surg Res,2022,273:100-109.DOI:10.1016/j.jss.2021.11.015.
[14] Martin GR,Wallace LE,Hartmann B,et al.Nutrient-stimulated GLP-2 release and crypt cell proliferation in experimental short bowel syndrome[J].Am J Physiol Gastrointest Liver Physiol,2005,288(3):G431-G438.DOI:10.1152/ajpgi.00242.2004.
[15] Helmrath MA,VanderKolk WE,Can G,et al.Intestinal adaptation following massive small bowel resection in the mouse[J].J Am Coll Surg,1996,183(5):441-449.
[16] Kokorina АA,Mikhailova EV,Krylova SA,et al.A model of short bowel syndrome in rodents in a long-term experiment[J].Bull Exp Biol Med,2022,172(6):779-784.DOI:10.1007/s10517-022-05477-4.
[17] Rubin DC,Levin MS.Mechanisms of intestinal adaptation[J].Best Pract Res Clin Gastroenterol,2016,30(2):237-248.DOI:10.1016/j.bpg.2016.03.007.
[18] Hines OJ,Bilchik AJ,Zinner MJ,et al.Adaptation of the Na+/glucose cotransporter following intestinal resection[J].J Surg Res,1994,57(1):22-27.DOI:10.1006/jsre.1994.1103.
[19] Dou Y,Lu X,Zhao J,et al.Morphometric and biomechanical remodelling in the intestine after small bowel resection in the rat[J].Neurogastroenterol Motil,2002,14(1):43-53.DOI:10.1046/j.1365-2982.2002.00301.x.
[20] Longshore SW,Wakeman D,McMellen M,et al.Bowel resection induced intestinal adaptation:progress from bench to bedside[J].Minerva Pediatr,2009,61(3):239-251.
[21] Tappenden KA.Pathophysiology of short bowel syndrome:considerations of resected and residual anatomy[J].JPEN J Parenter Enteral Nutr,2014,38(1 Suppl):14S-22S.DOI:10.1177/0148607113520005.
[22] Huang YH,Guo FL,Li YS,et al.Fecal microbiota signatures of adult patients with different types of short bowel syndrome[J].J Gastroenterol Hepatol,2017,32(12):1949-1957.DOI:10.1111/jgh.13806.
[23] Budinska E,Gojda J,Heczkova M,et al.Microbiome and metabolome profiles associated with different types of short bowel syndrome:implications for treatment[J].JPEN J Parenter Enteral Nutr,2020,44(1):105-118.DOI:10.1002/jpen.1595.
[24] Piper HG,Fan D,Coughlin LA,et al.Severe gut microbiota dysbiosis is associated with poor growth in patients with short bowel syndrome[J].JPEN J Parenter Enteral Nutr,2017,41(7):1202-1212.DOI:10.1177/0148607116658762.
[25] Pauline M,Fouhse J,Hinchliffe T,et al.Probiotic treatment vs empiric oral antibiotics for managing dysbiosis in short bowel syndrome:impact on the mucosal and stool microbiota,short-chain fatty acids,and adaptation[J].JPEN J Parenter Enteral Nutr,2022,46(8):1828-1838.DOI:10.1002/jpen.2377.
[26] O’Brien DP,Nelson LA,Huang FS,et al.Intestinal adaptation:structure,function,and regulation[J].Semin Pediatr Surg,2001,10(2):56-64.DOI:10.1053/spsu.2001.22383.
[27] Drucker DJ,Habener JF,Holst JJ.Discovery,characterization,and clinical development of the glucagon-like peptides[J].J Clin Invest,2017,127(12):4217-4227.DOI:10.1172/jci97233.
[28] Abdalqadir N,Adeli K.GLP-1 and GLP-2 orchestrate intestine integrity,gut microbiota,and immune system crosstalk[J].Microorganisms,2022,10(10):2061.DOI:10.3390/microorganisms10102061.
[29] Estall JL,Drucker DJ.Dual regulation of cell proliferation and survival via activation of glucagon-like peptide-2 receptor signaling[J].J Nutr,2003,133(11):3708-3711.DOI:10.1093/jn/133.11.3708.
[30] Reiner J,Berlin P,Wobar J,et al.Teduglutide promotes epithelial tight junction pore function in murine short bowel syndrome to alleviate intestinal insufficiency[J].Dig Dis Sci,2020,65(12):3521-3537.DOI:10.1007/s10620-020-06140-6.
[31] Hansen LB.GLP-2 and mesenteric blood flow[J].Dan Med J,2013,60(5):B4634.DOI:.
[32] Baldassano S,Amato A.GLP-2:what do we know? What are we going to discover?[J].Regul Pept,2014,194/195:6-10.DOI:10.1016/j.regpep.2014.09.002.
[33] Dubé PE,Brubaker PL.Frontiers in glucagon-like peptide-2:multiple actions,multiple mediators[J].Am J Physiol Endocrinol Metab,2007,293(2):E460-E465.DOI:10.1152/ajpendo.00149.2007.
[34] Brubaker PL.Glucagon-like peptide-2 and the regulation of intestinal growth and function[J].Compr Physiol,2018,8(3):1185-1210.DOI:10.1002/cphy.c170055.
[35] Bulut K,Pennartz C,Felderbauer P,et al.Glucagon like peptide-2 induces intestinal restitution through VEGF release from subepithelial myofibroblasts[J].Eur J Pharmacol,2008,578(2/3):279-285.DOI:10.1016/j.ejphar.2007.08.044.
[36] Wu JY,Ren WY,Li L,et al.Effect of aging and glucagon-like peptide 2 on intestinal microbiota in SD rats[J].Aging Dis,2018,9(4):566-577.DOI:10.14336/ad.2017.1001.
[37] Burness CB,McCormack PL.Teduglutide:a review of its use in the treatment of patients with short bowel syndrome[J].Drugs,2013,73(9):935-947.DOI:10.1007/s40265-013-0070-y.
[38] Kim ES,Keam SJ.Teduglutide:a review in short bowel syndrome[J].Drugs,2017,77(3):345-352.DOI:10.1007/s40265-017-0703-7.
[39] Rosete BE,Wendel D,Horslen SP.Teduglutide for pediatric short bowel syndrome patients[J].Expert Rev Gastroenterol Hepatol,2021,15(7):727-733.DOI:10.1080/17474124.2021.1913052.
[40] Lambe C,Talbotec C,Kapel N,et al.Long-term treatment with teduglutide:a 48-week open-label single-center clinical trial in children with short bowel syndrome[J].Am J Clin Nutr,2023,117(6):1152-1163.DOI:10.1016/j.ajcnut.2023.02.019.
[41] Chiba M,Masumoto K,Kaji T,et al.Efficacy and safety of teduglutide in infants and children with short bowel syndrome dependent on parenteral support[J].J Pediatr Gastroenterol Nutr,2023,77(3):339-346.DOI:10.1097/mpg.0000000000003867.
[42] Jeppesen PB,Pertkiewicz M,Messing B,et al.Teduglutide reduces need for parenteral support among patients with short bowel syndrome with intestinal failure[J].Gastroenterology,2012,143(6):1473-1481.e3.DOI:10.1053/j.gastro.2012.09.007.
[43] Jeppesen PB,Vanuytsel T,Subramanian S,et al.Glepaglutide,a long-acting glucagon-like peptide-2 analogue,reduces parenteral support in patients with short bowel syndrome:a phase 3 randomized controlled trial[J].Gastroenterology,2025,168(4):701-713.e6.DOI:10.1053/j.gastro.2024.11.023.
[44] Gigola F,Cianci MC,Cirocchi R,et al.Use of teduglutide in children with intestinal failure:a systematic review[J].Front Nutr,2022,9:866518.DOI:10.3389/fnut.2022.866518.
[45] 冯海霞,颜伟慧,陆丽娜,等.替度格鲁肽治疗儿童短肠综合征的单中心疗效和安全性分析[J].中华小儿外科杂志,2025,46(4):321-326.DOI:10.3760/cma.j.cn421158-20241030-00459. Feng HX,Yan WH,Lu LN,et al.Safety and efficacy analysis of teduglutide in children with short bowel syndrome:a single center study[J].Chin J Pediatr Surg,2025,46(4):321-326.DOI:10.3760/cma.j.cn421158-20241030-00459.
[46] Kocoshis SA,Merritt RJ,Hill S,et al.Safety and efficacy of teduglutide in pediatric patients with intestinal failure due to short bowel syndrome:a 24-week,phase III study[J].JPEN J Parenter Enteral Nutr,2020,44(4):621-631.DOI:10.1002/jpen.1690.
[47] Diamanti A,Lezo A,D’Antiga L,et al.Teduglutide in pediatric intestinal failure:a position statement of the Italian society of pediatric gastroenterology,hepatology and nutrition (SIGENP)[J].Dig Liver Dis,2022,54(10):1320-1327.DOI:10.1016/j.dld.2022.04.028.
[48] Bering J,DiBaise JK.Short bowel syndrome:complications and management[J].Nutr Clin Pract,2023,38(S1):S46-S58.DOI:10.1002/ncp.10978.
[49] Jeppesen PB,Gabe SM,Seidner DL,et al.Factors associated with response to teduglutide in patients with short-bowel syndrome and intestinal failure[J].Gastroenterology,2018,154(4):874-885.DOI:10.1053/j.gastro.2017.11.023.
[50] Norsa L,Ghirardi A,Ramos Boluda E,et al.Predictors of response and enteral autonomy in children with short bowel syndrome treated with teduglutide:a real-life multicentre cohort study[J].E Clinical Medicine,2025,85:103343.DOI:10.1016/j.eclinm.2025.103343.
[51] Vanuytsel T,Lakananurak N,Greif S,et al.Real-world experience with glucagon-like peptide 2 analogues in patients with short bowel syndrome and chronic intestinal failure:results from an international survey in expert intestinal failure centers[J].Clin Nutr ESPEN,2024,64:496-502.DOI:10.1016/j.clnesp.2024.10.161.
[52] Fifi A,Raphael BP,Terreri B,et al.Effects of teduglutide on diarrhea in pediatric patients with short bowel syndrome-associated intestinal failure[J].J Pediatr Gastroenterol Nutr,2023,77(5):666-671.DOI:10.1097/MPG.0000000000003922.
[53] Ramos Boluda E,Redecillas Ferreiro S,Manrique Moral O,et al.Experience with teduglutide in pediatric short bowel syndrome:first real-life data[J].J Pediatr Gastroenterol Nutr,2020,71(6):734-739.DOI:10.1097/mpg.0000000000002899.
[54] Jeppesen PB,Pertkiewicz M,Forbes A,et al.Quality of life in patients with short bowel syndrome treated with the new glucagon-like peptide-2 analogue teduglutide-analyses from a randomised,placebo-controlled study[J].Clin Nutr,2013,32(5):713-721.DOI:10.1016/j.clnu.2013.03.016.
[55] Oliveira SB,Kocoshis SA.Teduglutide for the treatment of short bowel syndrome:a double-edged sword?[J].Am J Clin Nutr,2023,117(6):1057-1058.DOI:10.1016/j.ajcnut.2023.04.009.
备注/Memo
收稿日期:2025-9-16。
基金项目:国家自然科学基金资助项目(82370525,82470541);上海市 "科技创新行动计划"医学创新研究专项项目(22Y31900600);上海市东方英才计划拔尖项目(BJWS2024033);上海市"医苑新星"青年医学人才项目(2023005);交大双百人研究型医师项目(2024009);卫健委卓越项目(20234Z0004)
通讯作者:王莹,Email:wangying02@xinhuamed.com.cn