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Tryptophan Metabolites in Irritable Bowel Syndrome: An Overnight Time-course Study

Journal of Neurogastroenterology and Motility 2019년 25권 4호 p.551 ~ 562
 ( Burr Robert L. ) - University of Washington Department of Biobehavioral Nursing and Health Informatics

 ( Gu Haiwei ) - University of Washington Department of Anesthesiology and Pain Medicine
 ( Cain Kevin C. ) - University of Washington Office for Nursing Research
 ( Djukovic Danijel ) - University of Washington Department of Anesthesiology and Pain Medicine
 ( Zhang Xinyu ) - University of Washington Department of Anesthesiology and Pain Medicine
 ( Han Claire ) - University of Washington Department of Biobehavioral Nursing and Health Informatics
 ( Callan Nini ) - National University of Natural Medicine Helfgott Research Institute
 ( Raftery Daniel ) - University of Washington Department of Anesthesiology and Pain Medicine
 ( Heitkemper Margaret ) - University of Washington Department of Biobehavioral Nursing and Health Informatics

Abstract


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.

Methods: 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.

Results: 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 (P = 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).

Conclusion: Nighttime Trp metabolites may provide clues to poor sleep and stress with IBS. Further study of the mechanism of metabolite action is warranted.

키워드

Irritable bowel syndrome; Melatonin; Sleep; Tryptophan
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