Use of magnetic resonance imaging to assess the effects of corticotrophin releasing factor on fructose malabsorption
Kathryn Murray1, Ching Lam2, Sumra Rehman3, Caroline Hoad1, Luca Marciani2, Carolyn Costigan1, Melanie Lingaya2, Rawinder Banwait2, Stephen Bawden1, Robin Spiller2, and Penny Gowland1

1Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, United Kingdom, 2NIHR Nottingham Digestive Diseases Biomedical Research Unit, University of Nottingham, Nottingham, United Kingdom, 3University of Nottingham, Nottingham, United Kingdom

Synopsis

A link between FODMAP malabsorption and stress has been suggested. Here, the effects of corticotrophin releasing factor (CRF) on fructose malabsorption are investigated in this randomised, placebo-controlled, crossover study in healthy volunteers.

Background

Food plays a role in causing the symptoms of irritable bowel syndrome (IBS). Poorly absorbed carbohydrates such as fructose are known as FODMAPs (fermentable oligo-di-mono-saccharides and polyhydric alcohols), and they tend to provoke symptoms of bloating, flatulence and pain in IBS patients1, 2. Fructose increases the volume of free water in the small bowel3. Any fructose not absorbed in the small bowel enters the colon, leading to an increase in colon volume. IBS is also associated with anxiety, and patients often report that its onset is associated with stress. Stress increases the transit of meals through the small bowel4, 5 and this may worsen the effects of malabsorption. Indeed, studies have indicated that anxiety is a strong predictor of developing symptoms after a FODMAPs meal6 although the mechanisms are unknown. Corticotrophin releasing factor (CRF) is capable of activating the body’s stress response and injections of CRF have been shown to reduce the volume of free water in the small bowel while increasing the volume of the ascending colon7. We hypothesised that stress increases the action of fructose by accelerating its transit into the colon, and we used CRF to test this.

Aim

To investigate the effect of intravenous injection of CRF on fructose malabsorption in healthy volunteers using MRI.

Methods

A randomised, placebo controlled, cross-over study of CRF versus saline injection in healthy subjects, examining its effect on the malabsorption of a 40 g fructose test meal and its transit through the gut was assessed by serial MRI. 20 healthy volunteers (10 female, (age 23 ± 3 years, BMI 24.4 ± 3.4 kgm-2) were randomised to take part. They attended for scanning twice and were asked to fast from 20:00 hrs on the prior day. MR scans were taken fasted, after which participants received an injection of either CRF or saline followed by a fructose meal. Scans were then taken every half hour for two hours, then hourly for another 2 hours. Images were collected using a whole-body, research-dedicated, 1.5T MR scanner (Achieva, Philips Medical System, Best, The Netherlands). The volume of water in the small bowel was measured and analysed as described previously8, using a coronal single-shot turbo spin-echo sequence. This acquired 24 slices in a single 24 second expiration breath hold (TR/TE = 8000/320 ms, 512x512 reconstructed matrix, voxel size 0.78x0.78x7 mm3). A coronal dual-echo gradient echo sequence was used to determine the volume of the ascending colon9. This sequence allowed 24 slice collection of both in-phase and out-of-phase images simultaneously in a single 15 second expiration breath hold (TR/TE1/TE2 = 157/2.30/4.60 ms, 256x256 reconstructed matrix, voxel size1.76x1.76x7 mm3). Gastric volumes were measured with a balanced gradient echo sequence (TR/TE = 2.98 / 1.49 ms, flip angle 80o, 256 x 256 reconstructed matrix, reconstructed in-plane resolution 1.56 x 1.56 x 5 mm3, SENSE 2.0) 10, acquiring 50 transverse slices in a 16.5 second breath hold.

Results

Small bowel water content (SBWC) increased from baseline, peaking at 45 minutes after fructose ingestion. The area under the curve (AUC) from -15 – 135 minutes postprandial was significantly lower after CRF (48.5 ± 15 L) relative to the placebo (55.9 ± 19 L, P = 0.04), also demonstrated on the MR images (Figure 1). Ascending colon volume (ACV) increased from baseline by 29% after injection with CRF (Figure 2) compared to an increase of 12% after injection with saline (P = 0.048). Notable differences were observed between female and male volunteers: males showed a significant increase in ACV) after CRF injection relative to the saline injection (47%, P = 0.04), while females registered a change of 8% between the two treatments (P = 0.7). Another difference between males and females was the rate of gastric emptying; CRF significantly delayed gastric emptying in female participants relative to the placebo (mean ± SD difference in AUC (t = -15 – t = 135 min) 5.1 ± 6.1 L.min, P = 0.027, t test), but this delay was not observed for the male participants (Figure 3).

Discussion/Conclusions

CRF is a chemical known to activate the stress response. We used MRI to show that CRF decrease in small bowel water volume compared to the placebo and increased ascending colon volumes, consistent with it constricting the small bowel and increasing fructose malabsorption. These observations help explain the increased sensitivity of some stressed individuals to fructose malabsorption. Differences were seen between male and female participants and the reasons for these differences require further exploration.

Acknowledgements

We thank the participants for their involvement. We are also grateful for the support of the NIHR Nottingham Digestive Diseases Biomedical Research Unit. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.

References

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Figures

Figure 1: An example of T2-weighted coronal MR images from the abdominal region of a single volunteer 45 minutes after a fructose drink. The SBWC after intravenous CRF (left) and saline (right) are compared.

The percentage change in ascending colon volume (ACV) for 20 volunteers from immediately before injection of CRF (●) or saline (▪) followed by a FODMAP drink. Injection time is indicated with the solid arrow, while the dashed arrow is time of drinking.

Mean ± SEM gastric volumes for (a) 10 male and (b)10 female volunteers after intravenous injection of CRF (●, solid connecting line) or saline (▪, dashed connecting line), followed by a FODMAP drink. Injection time is indicated with the solid arrow, the dashed arrow is time of drinking.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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