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

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.

Balance of Autonomic Nervous System Predicts Who Benefits from a Self-management Intervention Program for Irritable Bowel Syndrome

BACKGROUND/AIMS: To determine if potential biomarkers can be used to identify subgroups of people with irritable bowel syndrome (IBS) who will benefit the most or the least from a comprehensive self-management (CSM) intervention. METHODS: In a two-armed randomized controlled trial a CSM (n = 46) was compared to a usual care (n = 46) group with follow-up at 3 and 6 months post randomization. Biomarkers obtained at baseline included heart rate variability, salivary cortisol, interleukin-10 produced by unstimulated peripheral blood mononuclear cells, and lactulose/mannitol ratio. Linear mixed models were used to test whether these biomarkers predicted improvements in the primary outcomes including daily abdominal pain, Gastrointestinal Symptom score and IBS-specific quality of life. RESULTS: The nurse-delivered 8-session CSM intervention is more effective than usual care in reducing abdominal pain, reducing Gastrointestinal Symptom score, and enhancing quality of life. Participants with lower nighttime high frequency heart rate variability (vagal modulation) and increased low frequency/high frequency ratio (sympathovagal balance) had less benefit from CSM on abdominal pain. Salivary cortisol, IL-10, and lactulose/mannitol ratio were not statistically significant in predicting CSM benefit. Baseline symptom severity interacts with treatment, namely the benefit of CSM is greater in those with higher baseline symptoms. CONCLUSIONS: Cognitively-focused therapies may be less effective in reducing abdominal pain in IBS patients with higher sympathetic tone. Whether this a centrally-mediated patient characteristic or related to heightened arousal remains to be determined.