Corticotrophin releasing factor increases ascending colon volume after a fructose test meal in healthy humans: a randomised control trial

Murray, Kathryn; Lam, Ching; Rehman, Sumra; Marciani, Luca; Costigan, Carolyn; Hoad, Caroline; Lingaya, Melanie; Banwait, Rawinder; Bawden, Stephen; Gowland, Penny A.; Spiller, Robin C.

Abstract

Background: Poorly absorbed, fermentable carbohydrates can provoke irritable bowel syndrome (IBS) symptoms by escaping absorption in the small bowel and being rapidly fermented in the colon in some susceptible subjects. IBS patients are often anxious and stressed and stress accelerates small bowel transit which may exacerbate malabsorption.


Objective: In this study we investigated the effect of intravenous injection of corticotrophin releasing factor (CRF) on fructose malabsorption and the resulting volume of water in the small bowel.

Design: We performed a randomised, placebo controlled, cross-over study of CRF versus saline injection in 11 male and 10 female healthy subjects, examining the effect on the malabsorption of a 40 g fructose test meal and its transit through the gut which was assessed by serial Magnetic Resonance imaging (MRI) and breath hydrogen measurement. Orocaecal transit was assessed using the lactose-ureide C13 breath test and the adrenal response to CRF assessed by serial salivary cortisol measurements.
Results: (Mean ± SD) CRF injection caused a significant rise in salivary cortisol which lasted 135 minutes. Small bowel water content (SBWC) rose from baseline, peaking at 45 minutes after fructose ingestion while breath hydrogen peaked later at 75 minutes. The area under the curve (AUC) for SBWC from -15 - 135 minutes was significantly lower after CRF versus saline (mean difference [95% CI] 7433 [275, 14591] mL.min, P = 0.04). Ascending colon volume rose after CRF, significantly more for male volunteers than female (P = 0.025).


Conclusions: CRF constricts the small bowel and increases fructose malabsorption as shown by increased ascending colon volumes. This mechanism may help to explain the increased sensitivity of some stressed individuals to fructose malabsorption.


This trial was registered at ClinicalTrials.gov as NCT01763281

Citation

Murray, K., Lam, C., Rehman, S., Marciani, L., Costigan, C., Hoad, C., …Spiller, R. C. (2016). Corticotrophin releasing factor increases ascending colon volume after a fructose test meal in healthy humans: a randomised control trial. American Journal of Clinical Nutrition, 103(5), https://doi.org/10.3945/ajcn.115.125047

• Journal Article Type: Article
• Acceptance Date: Mar 16, 2016
• Online Publication Date: Apr 20, 2016
• Publication Date: May 31, 2016
• Deposit Date: Jan 26, 2017
• Publicly Available Date: Jan 26, 2017
• Journal: American Journal of Clinical Nutrition
• Print ISSN: 0002-9165
• Electronic ISSN: 1938-3207
• Publisher: Oxford University Press
• Peer Reviewed: Peer Reviewed
• Volume: 103
• Issue: 5
• DOI: https://doi.org/10.3945/ajcn.115.125047
• Keywords: Corticotropin-releasing factor, FODMAPs, Irritable bowel syndrome, Magnetic resonance imaging, Malabsorption
• Public URL: https://nottingham-repository.worktribe.com/output/787739
• Publisher URL: https://academic.oup.com/ajcn/article/103/5/1318/4569589
• Contract Date: Jan 26, 2017