全肠内营养治疗对克罗恩病患者血浆氨基酸水平的影响

The influence of exclusive enteral nutrition on plasma amino acid levels in patients with Crohn′s disease

目的:探讨全肠内营养(EEN)治疗对克罗恩病(CD)患者血浆氨基酸水平的影响。方法:前瞻性纳入2020年12月1日至2021年12月31日期间于中山大学附属第六医院就诊的成人中度及重度活动期CD患者。所有患者单用鼻饲EEN治疗8周,收集患者EEN治疗前后的临床资料并依据CD活动度评分(CDAI)将患者分为缓解组和非缓解组。同时收集患者的血浆标本,采用靶向代谢组学技术检测并分析EEN治疗前后、缓解组和非缓解组CD患者血浆中25种氨基酸水平的变化。结果:纳入13例中重度活动期CD患者。EEN治疗8周后,CD患者临床缓解率为69.2%(9/13)。对比EEN治疗前,EEN治疗8周后CD患者血浆中色氨酸、苏氨酸、丙氨酸、脯氨酸及半胱氨酸的水平显著升高,差异均有统计学意义(P均<0.05)。EEN治疗8周后,缓解组色氨酸代谢物吲哚乙酸及吲哚乙酰胺显著低于非缓解组,差异具有统计学意义(P均<0.05)。色氨酸与CDAI和红细胞沉降率呈负相关,犬尿氨酸与红细胞沉降率呈负相关。结论:EEN可有效诱导中度及重度活动期CD患者临床缓解。EEN治疗后血浆色氨酸、半胱氨酸、丙氨酸、脯氨酸、苏氨酸水平显著升高,其中色氨酸代谢可能是EEN起效的关键途径,结论有待进一步探讨。

Objective To investigate the effect of exclusive enteral nutrition(EEN)on plasma amino acid levels in patients with Crohn′s disease(CD).Methods Adult patients with moderate to severe active CD in the Sixth Affiliated Hospital of Sun Yat⁃sen University from December 1,2020 to December 31,2021 were prospectively recruited.All the participants received nasogastric EEN monotherapy for 8 weeks.Patients were divided into clinical response group and non⁃response group according to CD activity index(CDAI).Clinical data were collected from all the participants before and after EEN.Targeted metabolomics was used to detect and analyze the changes of 25 amino acids levels in plasma in CD patients before and after EEN,as well as the differences between response group and non⁃response group.Results Thirteen patients were included in the study.The clinical remission rate reached 69.2%(9/13)after 8 weeks of EEN treatment.Compared with pre⁃treatment,the plasma levels of tryptophan,threonine,alanine,proline and cysteine in CD patients were significantly higher after EEN treatment.At week 8 after EEN,tryptophan metabolites including indole acetic acid and indole acetamide were significantly lower in patients with clinical remission compared to patients without remission.Correlation analysis showed the plasma levels of tryptophan was negatively correlated with CDAI and erythrocyte sedimentation rate(ESR),and the level of kynurenine was negatively correlated with ESR.Conclusion EEN therapy is an effective way to induce clinical remission in active CD patients.After EEN,plasma levels of tryptophan,threonine,alanine,proline and cysteine are significantly increased.Tryptophan and cysteine metabolisms may be the key pathways leading to the efficacy of EEN treatment.