Burr Robert L, Gu Haiwei, Cain Kevin, Djukovic Danijel, Zhang Xinyu, Han Claire, Callan Nini, Raftery Daniel, Heitkemper Margaret
Department of Biobehavioral Nursing and Health Informatics, University of Washington, Seattle, WA, USA.
Office for Nursing Research, University of Washington, Seattle, WA, USA.
J Neurogastroenterol Motil. 2019 Oct 30;25(4):551-562. doi: 10.5056/jnm19042.
BACKGROUND/AIMS: Patients with irritable bowel syndrome (IBS) often report poor sleep quality. Whether poor sleep is associated with tryptophan (Trp) metabolites is unknown. We compared serum Trp metabolites in women with IBS and healthy controls (HCs) using targeted liquid chromatography mass spectrometry (LC-MS)-based profiling. In IBS only, we explored whether Trp metabolites are associated with IBS symptoms and subjective and objective sleep indices, serum cortisol, plasma adrenocorticotropic hormone (ACTH), and cortisol/ACTH levels.
Blood samples were obtained every 80 minutes in 21 HCs and 38 IBS subjects following an anticipation-of-public-speaking stressor during a sleep laboratory protocol. Subjects completed symptom diaries for 28 days. Adjacent values of metabolites were averaged to represent 4 time-periods: awake, early sleep, mid-sleep, and mid-to-late sleep. Thirteen of 20 targeted Trp metabolites were identified.
Ten of 13 Trp metabolites decreased across the night, while nicotinamide increased in both groups. A MANOVA omnibus test performed after principal component analysis showed a significant difference in these 13 principal component ( = 0.014) between groups. Compared to HCs, nicotinamide levels were higher and indole-3-lactic acid levels lower in the IBS group. Melatonin and indole-3-acetic acid levels were associated with several subjective/objective sleep measures; decreased stool consistency/frequency and abdominal pain were positively associated with melatonin and serotonin in the IBS group. The kynurenine and kynurenic acid were associated with ACTH (positively) and cortisol/ACTH (negatively).
Nighttime Trp metabolites may provide clues to poor sleep and stress with IBS. Further study of the mechanism of metabolite action is warranted.
背景/目的：肠易激综合征（IBS）患者常报告睡眠质量差。睡眠不佳是否与色氨酸（Trp）代谢产物有关尚不清楚。我们使用基于靶向液相色谱质谱（LC-MS）的分析方法，比较了IBS女性患者和健康对照者（HCs）的血清Trp代谢产物。仅在IBS患者中，我们探讨了Trp代谢产物是否与IBS症状、主观和客观睡眠指标、血清皮质醇、血浆促肾上腺皮质激素（ACTH）以及皮质醇/ACTH水平相关。
在睡眠实验室方案中，对21名HCs和38名IBS受试者在预期公开演讲应激源后，每80分钟采集一次血样。受试者完成28天的症状日记。将代谢产物的相邻值平均以代表4个时间段：清醒、早睡、中睡和睡到半夜。在20种靶向Trp代谢产物中鉴定出13种。
13种Trp代谢产物中有10种在夜间下降，而两组中的烟酰胺均增加。主成分分析后进行的多变量方差分析综合检验显示，两组之间这13个主成分存在显著差异（P = 0.014）。与HCs相比，IBS组的烟酰胺水平较高，吲哚-3-乳酸水平较低。褪黑素和吲哚-3-乙酸水平与几种主观/客观睡眠指标相关；IBS组中，粪便稠度/频率降低和腹痛与褪黑素和血清素呈正相关。犬尿氨酸和犬尿酸与ACTH（正相关）和皮质醇/ACTH（负相关）相关。
夜间Trp代谢产物可能为IBS患者睡眠不佳和应激提供线索。有必要进一步研究代谢产物作用的机制。
