Postprandial changes in gastrointestinal function and transit in cystic fibrosis assessed by Magnetic Resonance Imaging

Abstract

Background: Cystic fibrosis (CF) is a multi-system genetic disorder affecting > 72,0 0 0 people worldwide. Most CF patients experience gastrointestinal symptoms and can develop complications. However, the mechanisms of CF gut disease are not well understood. We evaluated gut function and transit in CF using magnetic resonance imaging (MRI). We hypothesised oro-caecal transit time (OCTT) is longer in CF; with lower small bowel water content (SBWC).Methods: Twelve CF patients aged 12-40 years and 12 age and sex-matched controls underwent serial MRIs over 1 day with standardised meals. The primary endpoint was OCTT, assessed by the appearance of a food bolus in the caecum. Other measures included corrected SBWC and corrected colonic volume (both area under the curve, AUC), gastric half-emptying time and gastrointestinal symptoms.Results: OCTT was longer in CF (CF 330 mins [270, > 360] vs. controls 210 mins [173, 315], p = 0.04), with no difference in gastric half-emptying times. Corrected SBWC was higher in CF (CF 62 L.min/m 2 [36, 80] vs. controls 34 L.min/m 2 [28, 41], p = 0.021); minimal postprandial decrease between T240 and T300 (CF 13 mL/m 2 [-13, 57] vs. controls 102 mL/m 2 [67, 108], p = 0.002) suggests impaired ileal emptying. Corrected colonic volumes were higher in CF (CF 186 L.min/m 2 [167, 206] vs. controls 123 L.min/m 2 [89, 146], p = 0.012). There were no differences in gastrointestinal symptoms.Conclusions: MRI provides novel insights into CF pathophysiology. Sub-clinical ileal obstruction may be more prevalent than previously thought. Gastrointestinal MRI shows promise as an investigational tool in CF.

Magnetic resonance imaging of the gastrointestinal tract shows reduced small bowel motility and altered chyme in cystic fibrosis compared to controls

“…This study aimed to investigate potential causes and consequences of prolonged oro-caecal transit in CF, which was previously observed by our group (Ng et al ., 2020) and others (Gelfond et al ., 2013). Gastrointestinal symptoms in CF are proposed to derive from a cycle of chyme stasis causing bacterial overgrowth, inflammation and further inhibition of motility.…”

“…This may be due to change in chyme consistency (caused by maldigestion) and to partial obstruction at the level of the ileocaecal valve. We cannot ascertain whether this reduction is a primary difference in contractile activity or a secondary effect of chronic distension as demonstrated by the higher small bowel water content (Ng et al ., 2020), chronic inflammation and fibrosis (Bruzzese et al ., 2014). Postprandial motility in CF appeared to become more similar to healthy controls.…”

“…This study was carried out as described previously (Ng et al ., 2020). In short, 12 people with CF (homozygous for p.Phe508del mutation, with a forced expiratory volume in 1 second (FEV 1 ) over 40% of predicted, 12-40 years of age; see (Ng et al ., 2020) for complete list of criteria and Table 1 for demographics) and 12 age and gender matched healthy controls participated in this study. None of the CF participants had CF-related diabetes, and only one had a history of DIOS.…”

“…We have previously reported primary and secondary outcomes from this study (Ng et al ., 2020), in which a higher small bowel water content suggested impaired stimulation of ileal emptying after eating (the gastro-ileal reflex (Deiteren et al ., 2010)) and obstructed transfer of small bowel chyme to the colon.…”

“…Here, we report exploratory outcomes testing the hypotheses that small bowel motility is reduced in CF which may result in prolonged small bowel transit (Ng et al ., 2020) compared to healthy controls, and that there is a difference in small bowel and colon chyme compared to that of healthy controls. Chyme water content as well as the composition of the chyme are considered, using subjective scoring and objective quantitative methods.…”