J Neurogastroenterol Motil.  2019 Oct;25(4):551-562. 10.5056/jnm19042.

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

Affiliations
  • 1Department of Biobehavioral Nursing and Health Informatics, University of Washington, Seattle, WA, USA. heit@uw.edu
  • 2Office for Nursing Research, University of Washington, Seattle, WA, USA.
  • 3Northwest Metabolomics Research Center, Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA.
  • 4Department of Biostatistics, University of Washington, Seattle, WA, USA.
  • 5Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • 6Helfgott Research Institute, National University of Natural Medicine, Portland, OR, USA.

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

Keyword

Irritable bowel syndrome; Melatonin; Sleep; Tryptophan

MeSH Terms

Abdominal Pain
Adrenocorticotropic Hormone
Chromatography, Liquid
Female
Humans
Hydrocortisone
Irritable Bowel Syndrome*
Kynurenic Acid
Kynurenine
Mass Spectrometry
Melatonin
Niacinamide
Plasma
Principal Component Analysis
Serotonin
Tryptophan*
Adrenocorticotropic Hormone
Hydrocortisone
Kynurenic Acid
Kynurenine
Melatonin
Niacinamide
Serotonin
Tryptophan
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