Corticotropin-releasing factor increases ascending colon volume after a fructose test meal in healthy humans: a randomized controlled trial.
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 often are anxious and stressed, and stress accelerates small bowel transit, which may exacerbate malabsorption.


OBJECTIVE
In this study we investigated the effect of an intravenous injection of corticotropin-releasing factor (CRF) on fructose malabsorption and the resulting volume of water in the small bowel.


METHODS
We performed a randomized, placebo-controlled crossover study of CRF compared with 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 MRI and breath hydrogen measurement. Orocecal transit was assessed with the use of the lactose [(13)C]ureide breath test and the adrenal response to CRF was assessed by serial salivary cortisol measurements.


RESULTS
CRF injection caused a significant increase in salivary cortisol, which lasted for 135 min. Small bowel water content (SBWC) rose from baseline, peaking at 45 min after fructose ingestion, whereas breath hydrogen peaked later, at 75 min. The area under the curve for SBWC from -15 min to 135 min was significantly lower after CRF compared with saline [mean difference: 5911 mL · min (95% CI: 18.4, 11,803 mL · min), P = 0.049]. Considering all subjects, the percentage change in ascending colon volume rose significantly after CRF. This increase was significant for male (P = 0.026), but not female, volunteers.


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.
Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy.
Kathryn A
KA
Murray
Nottingham Digestive Diseases Biomedical Research Unit, Nottingham University Hospitals, and Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, United Kingdom.
Ching
C
Lam
Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, United Kingdom.
Sumra
S
Rehman
Nottingham Digestive Diseases Biomedical Research Unit, Nottingham University Hospitals, and Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, United Kingdom.
Luca
L
Marciani
Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy.
Carolyn
C
Costigan
Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy.
Caroline L
CL
Hoad
Nottingham Digestive Diseases Biomedical Research Unit, Nottingham University Hospitals, and.
Melanie R
MR
Lingaya
Nottingham Digestive Diseases Biomedical Research Unit, Nottingham University Hospitals, and.
Rawinder
R
Banwait
Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy.
Stephen J
SJ
Bawden
Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy.
Penny A
PA
Gowland
Nottingham Digestive Diseases Biomedical Research Unit, Nottingham University Hospitals, and Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, United Kingdom robin.spiller@nottingham.ac.uk.
Robin C
RC
Spiller
D061605:Administration, Intravenous; D000328:Adult; D015992:Body Mass Index; D001944:Breath Tests; D044682:Colon, Ascending / Q000187:drug effects* / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005632:Fructose / Q000008:administration & dosage* / Q000009:adverse effects; D005746:Gastric Emptying / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis; D007421:Intestine, Small / Q000187:drug effects / Q000502:physiology; D043183:Irritable Bowel Syndrome / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008286:Malabsorption Syndromes / Q000503:physiopathology; D008297:Male; D062407:Meals; D019518:Postprandial Period; D012463:Saliva / Q000737:chemistry; D011795:Surveys and Questionnaires; D055815:Young Adult
D005632:Fructose; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone
FODMAPs; corticotropin-releasing factor; irritable bowel syndrome; magnetic resonance imaging; malabsorption