Gastrointestinal peptides and small bowel hypomotility are possible causes for fasting and postprandial symptoms in active Crohn’s disease

Khalaf, Asseel; Hoad, Caroline L.; Menys, Alex; Nowak, Adam; Radford, Shellie; Taylor, Stuart A.; Latief, Khalid; Lingaya, Melanie; Falcone, Yirga; Singh, Gulzar; Spiller, Robin C.; Gowland, Penny A.; Marciani, Luca; Moran, Gordon W.

Abstract

Background
Crohn's disease (CD) patients suffer postprandial aversive symptoms, which can lead to anorexia and malnutrition. Changes in the regulation of gut hormones and gut dysmotility are believed to play a role.

Objectives
This study aimed to investigate small-bowel motility and gut peptide responses to a standard test meal in CD by using MRI.

Methods
We studied 15 CD patients with active disease (age 36 ± 3 y; BMI 26 ± 1 kg/m 2) and 20 healthy volunteers (HVs; age 31 ± 3 years; BMI 24 ± 1 kg/m 2). They underwent baseline and postprandial MRI scans, symptom questionnaires, and blood sampling following a 400-g soup meal (204 kcal). Small-bowel motility, other MRI parameters, and glucagon-like peptide-1 (GLP-1), polypeptide YY (PYY), and cholecystokinin peptides were measured. Data are presented as means ± SEMs.

Results
HVs had significantly higher fasting motility indexes [106 ± 13 arbitrary units (a.u.)], compared with CD participants (70 ± 8 a.u.; P ≤ 0.05). Postprandial small-bowel water content showed a significant time by group interaction (P < 0.05), with CD participants showing higher levels from 210 min postprandially. Fasting concentrations of GLP-1 and PYY were significantly greater in CD participants, compared with HVs [GLP-1, CD 50 ± 8 µg/mL versus HV 13 ± 3 µg/mL (P ≤ 0.0001); PYY, CD 236 ± 16 pg/mL versus HV 118 ± 12 pg/mL (P ≤ 0.0001)]. The meal challenge induced a significant postprandial increase in aversive symptom scores (fullness, distention, bloating, abdominal pain, and sickness) in CD participants compared with HVs (P ≤ 0.05).

Conclusions
The decrease in fasting small-bowel motility noted in CD participants can be ascribed to the increased fasting gut peptides. A better understanding of the etiology of aversive symptoms in CD will facilitate identification of better therapeutic targets to improve nutritional status. This trial was registered at clinicaltrials.gov as NCT03052465.

• Journal Article Type: Article
• Acceptance Date: Aug 29, 2019
• Online Publication Date: Sep 26, 2019
• Publication Date: 2020-01
• Deposit Date: Sep 3, 2019
• Publicly Available Date: Sep 27, 2020
• Journal: American Journal of Clinical Nutrition
• Print ISSN: 0002-9165
• Electronic ISSN: 1938-3207
• Publisher: Oxford University Press
• Peer Reviewed: Peer Reviewed
• Volume: 111
• Issue: 1
• Pages: 131–140
• DOI: https://doi.org/10.1093/ajcn/nqz240
• Keywords: Gastrointestinal motility; gut peptides; Crohn’s disease; anorexia
• Public URL: https://nottingham-repository.worktribe.com/output/2554185
• Publisher URL: https://academic.oup.com/ajcn/advance-article/doi/10.1093/ajcn/nqz240/5574382
• Additional Information: This is a pre-copyedited, author-produced version of an article accepted for publication in American Journal of Clinical Nutrition following peer review. The version of record Asseel Khalaf, Caroline L Hoad, Alex Menys, Adam Nowak, Shellie Radford, Stuart A Taylor, Khalid Latief, Melanie Lingaya, Yirga Falcone, Gulzar Singh, Robin C Spiller, Penny A Gowland, Luca Marciani, Gordon W Moran, Gastrointestinal peptides and small-bowel hypomotility are possible causes for fasting and postprandial symptoms in active Crohn's disease, The American Journal of Clinical Nutrition, , nqz240 is available online at: https://academic.oup.com/ajcn/advance-article/doi/10.1093/ajcn/nqz240/5574382 and doi:10.1093/ajcn/nqz240