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

Abstract

Background/AimsPatients 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.MethodsBlood 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.ResultsTen 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).ConclusionsNighttime Trp metabolites may provide clues to poor sleep and stress with IBS. Further study of the mechanism of metabolite action is warranted.

Characteristics of fecal metabolic profiles in patients with irritable bowel syndrome with predominant diarrhea investigated using 1H‐NMR coupled with multivariate statistical analysis

“…Further studies are needed on the role of threonine in IBS‐D. Tryptophan, which is converted to serotonin, is known to be associated with IBS, as the increased serotonin levels lead to increased GI motility and visceral hypersensitivity . Previous studies have shown that patients with IBS‐D have comparatively higher levels of free serum tryptophan than those in HC .…”

Review article: current and future treatment approaches for pain in IBS

“…There appears to be an indirect effect of sleep problems on abdominal pain through daytime dysfunction in adults with irritable bowel syndrome, 83 furthermore the pineal gland circadian hormone melatonin levels were positively associated with decreased abdominal pain in IBS. 84 In a systematic review of exogenous supplementation of melatonin, all the small studies with significant heterogeneity, and low-quality evidence (Table 1) consistently showed improvement in abdominal pain for IBS. 85 Daytime sleepiness was the only side effect in some patients.…”

Proceedings of the Summer Institute on Symptoms and Omics

“…Poor sleep quality, including frequent awakenings, fatigue, and not feeling rested in the morning are symptoms commonly reported by women with IBS. Given the evidence that serotonin, the most well-known tryptophan metabolite, is involved in pain sensitivity, gut motility, gut function, and secretion (Costedio et al, 2007) and the common thinking that tryptophan is a precursor to melatonin, Dr Heitkemper conducted a targeted metabolomics study investigating the role of tryptophan metabolites in IBS symptoms and explored the association of these metabolites to sleep measures (Burr et al, 2019).…”

“…Using nocturnal blood samples collected from both IBS and healthy control subjects exposed to a social stressor, Heitkemper’s findings suggest that with the exception of nicotinamide, tryptophan metabolites decreased across the night in both controls and women with IBS (Burr et al, 2019). She also identified that compared to the control group, nicotinamide levels were higher and indole-3-lactic acid levels lower in the IBS group (Burr et al, 2019).…”

“…Using nocturnal blood samples collected from both IBS and healthy control subjects exposed to a social stressor, Heitkemper’s findings suggest that with the exception of nicotinamide, tryptophan metabolites decreased across the night in both controls and women with IBS (Burr et al, 2019). She also identified that compared to the control group, nicotinamide levels were higher and indole-3-lactic acid levels lower in the IBS group (Burr et al, 2019). Because blood levels of indole-3-lactic acid can indicate bacterial metabolism, these findings prompted an examination of the contribution of the gut microbiome to peripheral levels of tryptophan metabolites in a targeted metabolomics study of fecal samples.…”