炎症性肠病肠易激样症状研究进展

摘要

炎症性肠病患者在达到临床、内镜甚至组织学缓解后, 常持续存在腹痛、腹胀及排便习惯改变等肠易激综合征样症状, 严重影响患者生活质量并增加医疗负担. 该现象患病率较高, 其发病机制涉及遗传易感性、炎症后遗症、肠道微生态失调、内脏高敏感性及脑-肠互动障碍等多个层面. 临床诊断需首先排除活动性炎症及其他器质性病变. 治疗上应采取多模式综合管理, 结合生活方式调整、对症药物、神经调节剂及心理干预, 旨在改善症状并提升生活质量.

关键词: 炎症性肠病; 肠易激综合征; 综合管理; 脑-肠互动; 焦虑

核心提要: 炎症性肠病缓解期患者肠易激综合征样症状患病率高, 其机制复杂、多维交互; 临床诊断需首先排除活动性炎症及其他器质性病变. 治疗上应采取多模式综合管理, 结合生活方式调整、对症药物、神经调节剂及心理干预, 旨在改善症状并提升生活质量.

Irritable bowel syndrome like symptoms in inflammatory bowel disease: Research progress

Shi-Ming Zhou, Hai-Bing Dong, Kun Zhang, Bo Jiang

Shi-Ming Zhou, Hai-Bing Dong, Kun Zhang, Bo Jiang, Department of Gastroenterology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, Beijing 102218, China

Corresponding author: Bo Jiang, MD, Chief Physician, Department of Gastroenterology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, No. 168 Litang Road, Changping District, Beijing 102218, China. drjiang@163.com

Received: April 1, 2026
Revised: April 10, 2026
Accepted: April 24, 2026
Published online: April 28, 2026

Abstract

Patients with inflammatory bowel disease frequently experience persistent irritable bowel syndrome like symptoms, such as abdominal pain, bloating, and altered bowel habits, even after achieving clinical, endoscopic, or even histological remission. These symptoms significantly compromise patients' quality of life and increase the healthcare burden. This condition is highly prevalent, and its pathogenesis encompasses multiple dimensions, including genetic susceptibility, inflammatory sequelae, gut dysbiosis, visceral hypersensitivity, and disordered brain-gut interactions. Clinically, the diagnosis requires the initial exclusion of active inflammation and other organic pathologies. In terms of treatment, a comprehensive multimodal management strategy should be adopted, integrating lifestyle modifications, symptomatic pharmacotherapy, neuromodulators, and psychological interventions, with the aim of alleviating symptoms and improving quality of life.

Key Words: Inflammatory bowel disease; Irritable bowel syndrome; Comprehensive management; Brain-gut interaction; Anxiety

核心提要: 炎症性肠病缓解期患者肠易激综合征样症状患病率高, 其机制复杂、多维交互; 临床诊断需首先排除活动性炎症及其他器质性病变. 治疗上应采取多模式综合管理, 结合生活方式调整、对症药物、神经调节剂及心理干预, 旨在改善症状并提升生活质量.

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0 引言

炎症性肠病(inflammatory bowel disease, IBD), 主要包括克罗恩病(Crohn's disease, CD)和溃疡性结肠炎(ulcerative colitis, UC), 是一类慢性复发性炎症性疾病, 其治疗目标已从单纯控制症状逐步升级为达到内镜甚至组织学缓解[1,2]. 临床实践发现, 即使通过生物制剂或小分子药物实现了黏膜愈合, 部分患者仍持续存在腹痛、腹胀及排便习惯改变等胃肠道症状, 此类表现类似肠易激综合征(irritable bowel syndrome, IBS)[3].

IBS属于脑-肠互动障碍, 其诊断主要基于Rome Ⅳ等症状标准, 并需排除器质性疾病[3,4]. 尽管传统观念认为IBD与IBS的诊断互斥, 但研究证实IBD缓解期患者的症状谱与IBS高度重叠, 这一现象被称为"IBD合并IBS"或"IBS样症状"[5]. 流行病学数据显示, 该现象发生率显著高于普通人群, 严重影响患者生活质量, 并增加心理负担与医疗资源消耗[6]. 本文旨在系统综述IBD患者IBS样症状的流行病学、病理生理机制及临床管理策略, 以期为临床诊疗提供参考.

1 流行病学

流行病学研究证实了IBD患者IBS样症状的高发性及其临床重要性. Isgar等[7]报道内镜缓解期UC患者中IBS样症状患病率高达33%. Fairbrass等[8]对3169例缓解期IBD患者的分析显示, 临床、内镜及组织学缓解患者的IBS样症状患病率分别为32.5%、23.5%和25.8%, 且CD患者(36.6%)高于UC患者(28.7%). IBSEN研究[9]发现, 处于组织学缓解的UC患者IBS样症状患病率与活动期患者相当, 提示炎症并非症状的唯一驱动因素. 研究表明IBS样症状与IBD疾病活动度升高、激素使用需求增加等传统炎症指标无显著关联[10,11], 而与性别及焦虑、抑郁等心理共病密切相关[8,10]. 此类症状的持续存在不仅显著降低患者生活质量, 更导致门诊就诊与内镜检查频次增加, 造成沉重的医疗负担[8,10,12]. 除了横断面数据, IBS样症状在IBD病程中的纵向演变同样值得关注. Fairbrass等[10]的6年纵向随访研究显示, IBS样症状具有持续性, 且其存在与疾病活动度的波动无显著关联. 在疾病复发期, 功能性症状常与炎症活动交织, 进一步增加临床鉴别难度. 因此, 临床上需认识到IBS样症状在IBD全病程中均可能持续存在的动态特征(表1).

表1 IBD患者IBS样症状流行病学.

Ref.	疾病类型	活动情况	IBS样症状患病率	关键发现
Isgar等[7], 1983	UC	缓解期	33%	UC缓解期存在IBS症状
Halpin等[6], 2012	IBD	缓解期	39%	IBD患者中显著高于非IBD对照组
Henriksen等[9], 2018	UC	缓解期/活动期	总体: 27%; 组织学缓解: 29%	炎症并非症状唯一驱动因素
Fairbrass等[8], 2020	IBD	临床/内镜/组织学缓解	临床缓解: 32.5%; 内镜缓解: 23.5%; 组织学缓解: 25.8%	关注心理健康可能改善患者的治疗效果

IBD: 炎症性肠病; IBS: 肠易激综合征; UC: 溃疡性结肠炎.

2 病理生理机制

IBD患者IBS样症状的病理生理机制错综复杂, 其本质并非单纯的炎症残留或偶然共病, 而是涉及炎症后遗症、遗传易感性及脑-肠互动障碍等多维度因素的交互作用[13].

2.1 遗传易感性与环境因素

IBD与IBS存在共享的遗传易感性基础. 尽管IBS的遗传学研究起步较晚, 但已证实两者存在重叠的风险基因, 如TNFSF15基因多态性被证明同时增加CD与IBS的患病风险[14-16]. 一项西班牙研究[17]显示, IBD患者一级亲属的IBS患病率显著高于配偶对照组, 进一步佐证了遗传因素在症状重叠中的作用. 此外, 环境触发因素亦具有共性, 超加工食品的摄入已被证实可同时增加IBD和IBS的发病风险[18,19].

2.2 炎症后遗症与肠道微环境

"感染后IBS(Post-infection IBS, PI-IBS)"模型为理解IBD缓解期症状提供了重要视角. 胃肠道感染引发的低度炎症、屏障受损及菌群紊乱可在病原体清除后持续存在[13,20], 这与IBD急性发作后的肠道改变高度相似. 研究证实, 即便内镜下黏膜愈合, IBD患者仍可能存在微观层面的异常, 如嗜铬细胞增生、5-HT代谢改变、TRPV1阳性神经纤维增多及肥大细胞活化等[21-29]. 这些外周敏化改变是导致内脏高敏感性与肠道运动异常的重要基础. 肠道微生物群失调是另一关键环节[30,31]. IBD缓解期患者常表现出与IBS类似的菌群多样性降低或特定菌群比例失调[32-35]. 部分菌群代谢产物活性异常与症状严重度究[36]及肠道通透性增加密切相关[37].

2.3 内脏高敏感性与脑-肠互动障碍

内脏高敏感性是IBS的核心病理特征, 亦常见于缓解期IBD患者, 且其敏感程度与腹痛、腹胀等症状显著相关[38,39]. 其机制可能源于炎症后的神经重塑, 涉及肠神经系统伤害性感受纤维的敏化[40]. 脑-肠互动障碍在IBS样症状中发挥核心作用. 心理压力及焦虑抑郁状态通过激活下丘脑-垂体-肾上腺轴及自主神经系统, 影响肠道动力与黏膜屏障功能, 并加剧低度炎症或肥大细胞活化[41,42]. 反之, 源自肠道的持续病理信号亦可上行影响中枢, 调节情绪与疼痛感知[43,44]. 这种双向互动机制阐释了IBD患者心理共病与肠道症状之间的恶性循环.

2.4 5-羟色胺通路异常

5-羟色胺(5-hydroxytryptamine, 5-HT)通路异常是症状产生的重要分子机制. 急性炎症可破坏嗜铬细胞, 而慢性炎症或炎症后遗症则常导致嗜铬细胞增生及5-HT释放增加[45]. 研究发现[46], IBS-D患者直肠黏膜5-HT释放增加且与疼痛严重度相关. 在IBD缓解期, 尽管嗜铬细胞数量可能恢复正常, 但限速酶TPH-1表达上调提示5-HT周转率升高[47], 这可能成为治疗IBS样症状的潜在靶点.

3 诊断评估

对IBD患者新发或持续胃肠道症状的首要任务是鉴别活动性炎症与IBS样症状. 诊断过程需遵循结构化步骤:

3.1 排除活动性炎症

首先应通过客观指标确证炎症缓解, 评估内容涵盖临床缓解状态、生物标志物(C 型反应性蛋白、粪便钙卫蛋白)检测及内镜与组织学检查[9,48]. 鉴于部分患者内镜下黏膜外观正常而显微镜下仍存在炎症浸润, 组织学评估尤为重要. 临床实践中需结合实际情况综合判断, 避免过度活检增加患者负担. 若症状与炎症指标不符, 建议行肠道超声等影像学检查以评估透壁性愈合情况.

3.2 评估IBS样症状

在确认炎症缓解后, 应依据主要症状特征(如疼痛/腹胀主导型或排便习惯改变主导型)进行分类, 以指导治疗决策. 同时, 需尽早筛查焦虑、抑郁等心理共病, 因其不仅影响症状体验, 亦是预测治疗反应的关键因素[44,49].

3.3 鉴别诊断

尚需排除其他器质性或功能性病因. 例如, CD患者回盲部切除术后需警惕胆汁酸腹泻[50]; 多发狭窄或术后患者应排除小肠细菌过度生长; 此外需鉴别乳糖不耐受、乳糜泻及甲状腺功能异常等[48]; 以便秘为主者则应考虑排便协同失调或梗阻可能[5].

3.4 确立诊断

经上述排查, 若症状符合IBS特征且无其他合理解释, 可确立IBD患者IBS样症状的诊断. 诊断过程中应积极向患者阐释症状性质, 避免因反复检查延误"功能性"诊断的提出, 以利于建立医患信任并及时启动治疗(图1).

图1 IBD患者IBS样症状的诊断评估与处理流程图. IBD: 炎症性肠病; IBS: 肠易激综合征.

4 治疗策略: 多模式与个体化综合管理

目前尚无针对IBD合并IBS样症状的特异性疗法, 临床策略主要借鉴IBS管理经验, 结合IBD患者的病理生理特征, 采取多模式、个体化的综合治疗方案. 鉴于此类症状严重影响患者生活质量且常规抗炎治疗无效, 在IBD的全程管理中, 亟需将非炎症性症状的控制纳入整体治疗目标.

4.1 基础治疗: 生活方式与饮食调整

生活方式干预是治疗的基石, 建议患者保持规律运动、充足睡眠并进行压力管理. 饮食调整同样关键, 虽然长期盲目限制饮食易导致营养不良, 但针对性干预疗效确切. 其中, 低FODMAP饮食证据最为充分, 可有效缓解部分IBD患者的IBS样症状[51,52]. 长期实施低FODMAP饮食可能存在不良反应, 实施时建议在营养师指导下, 通过严格的限制与重新引入阶段, 识别个体化触发食物. 此外, 地中海饮食模式可作为整体健康饮食框架推荐[53].

4.2 针对肠道动力的对症治疗

针对腹泻型症状, 可选用洛哌丁胺等止泻药; 5-HT3受体拮抗剂(如昂丹司琼)在IBS-D中证实有效, 可延缓肠道传输并减轻腹泻[54]. 针对便秘型症状, 推荐使用渗透性泻剂或促分泌剂(如利那洛肽)[55]. 解痉药(如薄荷油、莨菪碱类)可用于缓解腹痛及肠道痉挛[56].

4.3 神经调节剂与心理干预

神经调节剂是改善腹痛及疼痛性排便障碍的重要药物. 小剂量三环类抗抑郁药(如阿米替林)兼具抗胆碱能止泻作用与中枢镇痛效应[57]; 选择性5-HT再摄取抑制剂(如艾司西酞普兰)及5-HT去甲肾上腺素再摄取抑制剂(如度洛西汀)适用于合并焦虑抑郁者, 且具有独立镇痛效果[58]. 使用时应从小剂量起始, 逐渐滴定. 但需注意, 三环类抗抑郁药及选择性5-HT再摄取抑制剂存在药物不良反应, 用药期间需密切监测患者反应及药物耐受性. 心理干预, 如认知行为疗法、正念减压疗法和肠道导向催眠疗法在IBS中疗效确切, 可调节脑-肠互动, 改善患者的认知应对策略与生活质量, 同样适用于IBD患者[59].

4.4 靶向微生物群与免疫调节

益生菌、益生元及合生元的疗效证据尚存异质性, 特定菌株(如乳酸杆菌、双歧杆菌)可能对缓解IBS及UC患者症状有益[60,61]. 粪便微生物移植在IBS中长期疗效不明, 且在IBD中结果参差不齐, 暂不作为常规推荐[62]. 针对潜在的免疫激活机制, 非特异性抗炎药(如5-氨基水杨酸类)总体疗效有限, 未来研究方向聚焦于蛋白酶抑制剂等更精准的免疫调节治疗[5,63].

5 结论

IBD治疗目标已由单纯控制炎症转向恢复生活质量[64]. IBS样症状是IBD缓解期的重要临床挑战, 其机制涉及遗传、微环境及脑-肠互动的多维交互. 在确认黏膜愈合后, 临床管理应积极采用以症状为导向、包含生活方式调整、对症药物、神经调节剂、心理干预及饮食疗法在内的多模式综合策略. 未来研究应聚焦于深化机制理解、发展精准诊断工具及验证个体化治疗方案, 最终实现对IBD患者全方位、全周期的健康照护, 真正达成恢复生活质量的治疗终极目标.

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学科分类: 胃肠病学和肝病学

手稿来源地: 北京市

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