ACM Advances in Clinical Medicine 2161-8712 Scientific Research Publishing 10.12677/acm.2024.1441206 ACM-85085 ACM20240400000_20537474.pdf 医药卫生 克罗恩病排除饮食在儿童克罗恩病中的应用 The Application of Crohn’s Disease Exclusion Diet in Children with Crohn’s Disease 秦 欢 2 1 王 玉婷 2 1 重庆医科大学附属儿童医院消化科，儿童发育疾病研究教育部重点实验室，国家儿童健康与疾病临床医学研究中心，儿童发育重大疾病国家国际科技合作基地，儿科学重庆市重点实验室，重庆 null 03 04 2024 14 04 1660 1665 © Copyright 2014 by authors and Scientific Research Publishing Inc. 2014 This work is licensed under the Creative Commons Attribution International License (CC BY). http://creativecommons.org/licenses/by/4.0/

儿童克罗恩病(CD)的发病率不断升高，饮食在克罗恩病的发生发展中起着重要作用，且克罗恩病患儿易出现营养不良问题，营养治疗显得尤为重要。指南推荐将全肠内营养(EEN)作为一线诱导缓解方案，但EEN具有不耐受等问题，克罗恩病排除饮食(CDED)联合部分肠内营养(PEN)具有比EEN耐受性好等优势，是目前的研究热点。本文旨在对CDED联合PEN在儿童克罗恩病中的应用进行阐述，为营养治疗在儿童克罗恩病中的应用提供新的思路。 The incidence of Crohn’s disease (CD) in children is increasing, diet plays an important role in the occurrence and development of Crohn’s disease, and children with Crohn’s disease are prone to malnutrition, and nutrition therapy is particularly important. Guidelines recommend exclusive enteral nutrition (EEN) as a first-line regimen to induce remission, but there is a problem with EEN that is not tolerated. Crohn’s disease exclusion diet (CDED) with partial enteral nutrition (PEN) has the advantage of better tolerance than EEN, and is a research hotspot. This article aims to elaborate the application of CDED with PEN in children with Crohn’s disease, and to provide new ideas for the application of nutrition therapy in children with Crohn’s disease.

 克罗恩病，儿童，克罗恩病排除饮食，部分肠内营养, Crohn’s Disease Child Crohn’s Disease Exclusion Diet Partial Enteral Nutrition 摘要

儿童克罗恩病(CD)的发病率不断升高，饮食在克罗恩病的发生发展中起着重要作用，且克罗恩病患儿易出现营养不良问题，营养治疗显得尤为重要。指南推荐将全肠内营养(EEN)作为一线诱导缓解方案，但EEN具有不耐受等问题，克罗恩病排除饮食(CDED)联合部分肠内营养(PEN)具有比EEN耐受性好等优势，是目前的研究热点。本文旨在对CDED联合PEN在儿童克罗恩病中的应用进行阐述，为营养治疗在儿童克罗恩病中的应用提供新的思路。

 关键词

克罗恩病，儿童，克罗恩病排除饮食，部分肠内营养

 The Application of Crohn’s Disease Exclusion Diet in Children with Crohn’s Disease<sup> </sup>

Huan Qin, Yuting Wang*

Department of Gastroenterology, Children’s Hospital of Chongqing Medical University, The Ministry of Education Key Laboratory of Child Development Disease Research, National Clinical Research Center for Child Health and Disease, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatric, Chongqing

Received: Mar. 23rd, 2024; accepted: Apr. 16th, 2024; published: Apr. 23rd, 2024

 ABSTRACT

The incidence of Crohn’s disease (CD) in children is increasing, diet plays an important role in the occurrence and development of Crohn’s disease, and children with Crohn’s disease are prone to malnutrition, and nutrition therapy is particularly important. Guidelines recommend exclusive enteral nutrition (EEN) as a first-line regimen to induce remission, but there is a problem with EEN that is not tolerated. Crohn’s disease exclusion diet (CDED) with partial enteral nutrition (PEN) has the advantage of better tolerance than EEN, and is a research hotspot. This article aims to elaborate the application of CDED with PEN in children with Crohn’s disease, and to provide new ideas for the application of nutrition therapy in children with Crohn’s disease.

Keywords:Crohn’s Disease, Child, Crohn’s Disease Exclusion Diet, Partial Enteral Nutrition

Copyright © 2024 by author(s) and beplay安卓登录

This work is licensed under the Creative Commons Attribution International License (CC BY 4.0).

http://creativecommons.org/licenses/by/4.0/

 1. 引言

克罗恩病(Crohn’s Disease, CD)是炎症性肠病(Inflammatory Bowel Disease, IBD)的一种亚型，是一种慢性肉芽肿炎症，病变呈透壁性炎症。儿童克罗恩病的发病率和患病率都在增加 [ 1 ] 。环境因素在CD的发病中起着重要作用 [ 2 ] ，如一些环境因素会引起儿童表观基因组的变化，从而影响疾病的易感性 [ 3 ] 。饮食是可以改变的环境危险因素 [ 4 ] ，如蔗糖摄入是CD的危险因素，水果摄入是CD的保护因素 [ 5 ] ，而且儿童CD营养不良很常见，CD治疗后仍可持续存在 [ 6 ] ，营养治疗在儿童克罗恩病治疗中起着重要作用。2021版中国炎症性肠病营养诊疗共识 [ 7 ] 和2020 ESPGHAN-ECCO共识指南 [ 8 ] 都推荐将全肠内营养(Exclusive Enteral Nutrition, EEN)作为轻中度儿童CD诱导缓解的一线治疗方法，但EEN存在耐受性不良、可持续性不佳、可能出现再进食综合征等 [ 9 ] 副作用、恢复自由饮食后出现反弹 [ 10 ] ，会影响患者的生活质量 [ 7 ] ，产生心理问题。近年来一些定制饮食方案被提出，饮食干预与管理将更多地应用于临床 [ 11 ] 。相关研究 [ 10 ] [ 12 ] 发现克罗恩病排除饮食(Crohn’s Disease Exclusion Diet, CDED)联合部分肠内营养(Partial Enteral Nutrition, PEN)耐受性优于EEN，且诱导儿童CD持续缓解，为儿童CD营养治疗提供新的思路。2023版ESPEN炎症性肠病的营养指南建议对于轻度至中度的儿童CD患者，应考虑将CDED加PEN作为EEN的替代方案，以达到缓解 [ 13 ] 。

 2. 克罗恩病排除饮食联合部分肠内营养的概念 2.1. 克罗恩病排除饮食(Crohn’s Disease Exclusion Diet, CDED)

克罗恩病排除饮食(CDED)由Arie Levin教授团队于2014年首次提出 [ 14 ] ，CDED饮食可粗略地定义为：循序渐进的高蛋白、低动物脂肪、低红肉类、低麸质、低添加剂饮食。CDED遵循排除和包容的原则，将食物分成必需食物、允许食物、限制食物三类 [ 9 ] 。必需食物包括含果胶和抗性淀粉的水果和蔬菜等，限制的食物主要包括动物脂肪、小麦成分、乳制品、红肉、麦芽糊精、乳化剂、卡拉胶、咖啡、酒精等，可以添加的积极食物主要包括水果、蔬菜、鸡肉、鸡蛋、大米等。

 2.2. 部分肠内营养(Partial Enteral Nutrition, PEN)

肠内营养是指通过口服或者管饲液体营养配方提供人体所需的营养元素，包括全肠内营养(EEN)和部分肠内营养(PEN)，部分肠内营养(PEN)是指35%至50%的摄入量由肠内营养替代，同时继续食用不受限制的饮食或排除饮食 [ 15 ] 。

 2.3. 克罗恩排除饮食联合部分肠内营养(CDED + PEN)

克罗恩病排除性饮食(CDED)联合部分肠内营养(PEN)包括三个阶段。第一阶段要求去除会引发炎症的食物成分，还限制一些水果和蔬菜的摄入量，以避免摄入过量的膳食纤维 [ 9 ] [ 16 ] 。只允许摄入鸡胸肉、鸡蛋、肠内营养作为动物蛋白的来源，必需摄入一些含有果胶和抗性淀粉的水果和蔬菜，由PEN提供50%的营养需求。第二阶段，PEN占总摄入量的比例减少到25%，允许纳入更多种类的食物。可以控制性地引入一些第一阶段不允许纳入的食物，如麸质、红肉和豆类等，但需限制牛肉和豆类的数量，不再限制纤维摄入量。第一、第二阶段各维持六周。第三阶段是维持阶段，需长期维持健康的生活方式，间歇性纳入第一阶段不允许的食物，维持饮食平衡，建议保持PEN占总摄入量25%的比例。第三阶段不需要强制性摄入必需食物，可以采用工作日和周末两种不同的饮食模式。在工作日，患者可以摄入第二阶段的所有食物，在周末，患者可以同家人一同食用家庭自制的自由饮食。若患者又出现炎症活动表现，则在一定时间内再次执行第一阶段饮食方案。具体实施过程中需要加强医生、营养师与患儿家属的沟通，制定合理的饮食方案，还可以通过网站、APP分享食谱 [ 9 ] [ 17 ] 。

 3. 克罗恩病排除饮食加部分肠内营养的作用机制

饮食在CD发生发展中起着重要的作用，饮食引起的代谢应激会促进肠道炎症 [ 18 ] ，高炎症饮食模式会增加患CD的风险 [ 19 ] 。CDED + PEN旨在限制所有对肠道微生物群、肠道屏障有负面影响的饮食成分，以及纳入对肠道有益的积极食物。

CDED + PEN纠正肠道菌落生态失调能力比EEN强，而且可以避免EEN恢复自由饮食后引起的肠道菌群生态失调的反弹。一项前瞻性、随机对照试验 [ 20 ] ，纳入轻至中度的儿童克罗恩病患者分别进行CDED + PEN (前六周CDED + 50% PEN，6~12周CDED + 25% PEN)和EEN (前六周EEN，6~12周自由饮食 + 25% PEN)治疗，收集达到临床缓解患者的粪便进行宏基因组分析及测量粪便中短链脂肪酸(Short-Chain Fatty Acids，SCFAs，肠道细菌的代谢产物，能够加强肠道屏障的完整性，调节免疫反应 [ 21 ] )浓度，并且与26名健康儿童粪便宏基因组数据进行对照分析。该试验发现在第六周时，两种营养方案都使CD患者变形菌门明显减少、厚壁菌门明显增加，但变形菌门丰度相对于健康对照组仍较高。12周结束后CDED + PEN组患者变形菌门进一步减少且逐渐接近健康对照组，EEN组变形菌门丰度反而上升。

CDED + PEN诱导持续缓解与代谢组的持续变化有关，而EEN恢复部分自由饮食后不能维持代谢组的持续变化 [ 22 ] 。CD患者犬尿氨酸途径会过度激活，炎症期间犬尿氨酸含量会增加。CDED + PEN诱导的缓解作用与犬尿氨酸和琥珀酸合成的减少和N-α-乙酰精氨酸的增加有关 [ 12 ] 。琥珀酸可以通过其特异性表面受体琥珀酸受体1激活免疫细胞，增强炎症和促炎细胞因子的分泌 [ 12 ] 。胃肠道中的菌群是犬尿氨酸的重要来源，肠道菌群可以直接吸收色氨酸产生激活芳香烃受体的色氨酸代谢产物，其中一些对炎症性肠病有保护作用。犬尿氨酸–多胺(精氨酸)–芳香烃受体免疫调节回路可以由肠道微生物群产生，维持肠上皮屏障、刺激胃肠蠕动、调节免疫 [ 23 ] 。

CDED + PEN能改变肠道通透性。Arie Levine等 [ 24 ] 研究发现，经过三周的CDED + PEN治疗，儿童CD患者肠通透性试验L/M正常占比增加。肠道微生物及代谢产物可通过与肠道上皮细胞的相互作用来增强肠道屏障功能 [ 22 ] 。

 4. 克罗恩排除饮食加部分肠内营养在治疗儿童CD中的应用 4.1. CDED + PEN在诱导轻中度儿童克罗恩病患者临床缓解的应用

一项前瞻性随机对照试验 [ 10 ] 发现，CDED + PEN诱导轻中度儿童克罗恩病患者临床缓解比例明显高于EEN，且可持续诱导缓解：第十二周CDED + PEN无激素缓解率75.6%，EEN组无激素持续缓解率45.1% (P = 0.01; Delta 30.5%; 95% CI 10.4%~52.6%; OR = 3.77; 95% CI 1.34~10.59)差异有统计学意义。第十二周CRP达正常CDED + PEN组75.9%，EEN组47.6% (P = 0.04; Delta 28.3%; 95% CI 1.9%~54.7%; OR 3.45; 95% CI 1.03~11.55)，差异有统计学意义。CDED + PEN组使粪钙卫蛋白浓度持续下降，EEN组六周后开始增加，CDED + PEN持续减轻肠道炎症可能优于EEN。CDED + PEN的耐受性也优于EEN：经过六周的治疗CDED + PEN组的耐受率为97.5%，EEN组为73.7%，CDED + PEN的耐受性明显优于EEN (P = 0.002 (Delta 23.8%; 95% CI 9.0%~38.6%); OR = 13.92 (95% CI 1.68~115.14))差异具有统计学意义。

 4.2. CDED + PEN在儿童克罗恩病生物制剂治疗失败患者中的应用

克罗恩病(CD)对生物制剂的失应答是一个重要的临床问题，即使剂量增加和联合治疗仍可能发生，越来越多的患者在使用第二种生物制剂后仍发生失应答，几乎没有其他治疗可以应用。一项回顾性研究 [ 25 ] 发现CDED + PEN对应用生物制剂治疗失败的CD患儿临床缓解有效。该研究纳入了21例患者。13例患者(62%)生物制剂剂量增加治疗失败，17例患者(81%)使用了英夫利昔单抗和阿达木单抗联合治疗失败，10例患者(47.6%)第二次生物治疗失败。13例患者(61.9%)在6周的CDED + PEN治疗后获得临床缓解。19例患者(90.4%)有临床反应(HBI至少减少3分)。在联合治疗失败的患者中，9例患者(53%)进入缓解期。该研究证明CDED + PEN对应用生物制剂治疗失败的CD患儿临床缓解有效，但该研究具有样本量小等局限性。

 4.3. CDED + PEN可诱导部分儿童CD患者快速反应或缓解

Rotem Sigall Boneh等 [ 26 ] 研究发现CDED + PEN可诱导部分儿童活动性克罗恩病患者快速反应或缓解(3周内儿童克罗恩病活动指数(Pediatric Crohn’s Disease Activity Index, PCDAI)小于12.5为快速反应，PCDAI小于10为快速缓解)，是第六周能否缓解和第12周能否持续缓解的重要预测因素。该研究分析了73例轻度至中度儿童CD患者的数据，39例进行了CDED + PEN方案治疗，34例进行了EEN方案治疗。73例患者中有61例(83.5%)在第3周有反应，73例患者中有46例(63%)在第3周缓解。在第3周的61例快速反应患者中，46例(75.4%)随后在第6周实现缓解。快速反应支持进一步CDED + PEN治疗，没有反应的患者可能不适合营养治疗，可以尽早使用其他治疗方法。

 5. 总结

总的来说，虽然关于CDED + PEN在儿童CD患者中的应用相关研究较少，但已提示CDED + PEN可以诱导轻中度儿童CD患者临床缓解，且诱导缓解比例高于EEN、耐受性优于EEN。此外，CDED + PEN还可以诱导生物制剂治疗失败的儿童CD患者的临床缓解，提示该方案具有较好的临床前景。但需注意的是，CDED可能会导致回避/限制性摄食障碍(Avoidant/Restrictive Food Intake Disorder, ARFID)，增加营养不良风险 [ 27 ] ，因此，对于CDED + PEN疗法仍需要进一步研究，制定更加细化优质的方案。

 文章引用

秦 欢,王玉婷. 克罗恩病排除饮食在儿童克罗恩病中的应用The Application of Crohn’s Disease Exclusion Diet in Children with Crohn’s Disease[J]. 临床医学进展, 2024, 14(04): 1660-1665. https://doi.org/10.12677/acm.2024.1441206

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