Kathryn Murray

Differential Effects of FODMAPs (Fermentable Oligo-, Di-, Mono-Saccharides and Polyols) on Small and Large Intestinal Contents in Healthy Subjects Shown by MRI

OBJECTIVES:The objective of this study was to investigate whether ingestion of fructose and fructans (such as inulin) can exacerbate irritable bowel syndrome (IBS) symptoms. The aim was to better understand the origin of these symptoms by magnetic resonance imaging (MRI) of the gut. METHODS: A total of 16 healthy volunteers participated in a four-way, randomized, single-blind, crossover study in which they consumed 500 ml of water containing 40 g of either glucose, fructose, inulin, or a 1:1 mixture of 40 g glucose and 40 g fructose. MRI scans were performed hourly for 5 h, assessing the volume of gastric contents, small bowel water content (SBWC), and colonic gas. Breath hydrogen (H2) was measured and symptoms recorded after each scan.RESULTS:Data are reported as mean (s.d.) (95% CI) when normally distributed and median (range) when not. Fructose increased area under the curve (AUC) from 0–5 h of SBWC to 71 (23) l/min, significantly greater than for glucose at 36 (11–132) l/min (P<0.001), whereas AUC SBWC after inulin, 33 (17–106) l/min, was no different from that after glucose. Adding glucose to fructose decreased AUC SBWC to 55 (28) l/min (P=0.08) vs. fructose. Inulin substantially increased AUC colonic gas to 33 (20) l/min, significantly greater than glucose and glucose+fructose (both P<0.05). Breath H2 rose more with inulin than with fructose. Glucose when combined with fructose significantly reduced breath H2 by 7,700 (3,121–12,300) p.p.m./min relative to fructose alone (P<0.01, n=13).CONCLUSIONS:Fructose but not inulin distends the small bowel with water. Adding glucose to fructose reduces the effect of fructose on SBWC and breath hydrogen. Inulin distends the colon with gas more than fructose, but causes few symptoms in healthy volunteers.

Quantification of Gastrointestinal Liquid Volumes and Distribution Following a 240 mL Dose of Water in the Fasted State

The rate and extent of drug dissolution and absorption from solid oral dosage forms is highly dependent upon the volumes and distribution of gastric and small intestinal water. However, little is known about the time courses and distribution of water volumes in vivo in an undisturbed gut. Previous imaging studies offered a snapshot of water distribution in fasted humans and showed that water in the small intestine is distributed in small pockets. This study aimed to quantify the volume and number of water pockets in the upper gut of fasted healthy humans following ingestion of a glass of water (240 mL, as recommended for bioavailability/bioequivalence (BA/BE) studies), using recently validated noninvasive magnetic resonance imaging (MRI) methods. Twelve healthy volunteers underwent upper and lower abdominal MRI scans before drinking 240 mL (8 fluid ounces) of water. After ingesting the water, they were scanned at intervals for 2 h. The drink volume, inclusion criteria, and fasting conditions matched the international standards for BA/BE testing in healthy volunteers. The images were processed for gastric and intestinal total water volumes and for the number and volume of separate intestinal water pockets larger than 0.5 mL. The fasted stomach contained 35 ± 7 mL (mean ± SEM) of resting water. Upon drinking, the gastric fluid rose to 242 ± 9 mL. The gastric water volume declined rapidly after that with a half emptying time (T50%) of 13 ± 1 min. The mean gastric volume returned back to baseline 45 min after the drink. The fasted small bowel contained a total volume of 43 ± 14 mL of resting water. Twelve minutes after ingestion of water, small bowel water content rose to a maximum value of 94 ± 24 mL contained within 15 ± 2 pockets of 6 ± 2 mL each. At 45 min, when the glass of water had emptied completely from the stomach, total intestinal water volume was 77 ± 15 mL distributed into 16 ± 3 pockets of 5 ± 1 mL each. MRI provided unprecedented insights into the time course, number, volume, and location of water pockets in the stomach and small intestine under conditions that represent standard BA/BE studies using validated techniques. These data add to our current understanding of gastrointestinal physiology and will help improve physiological relevance of in vitro testing methods and in silico transport analyses for prediction of bioperformance of oral solid dosage forms, particularly for low solubility Biopharmaceutics Classification System (BCS) Class 2 and Class 4 compounds.

Stimulation of colonic motility by oral PEG electrolyte bowel preparation assessed by MRI: comparison of split vs single dose

Most methods of assessing colonic motility are poorly acceptable to patients. Magnetic resonance imaging (MRI) can monitor gastrointestinal motility and fluid distributions. We predicted that a dose of oral polyethylene glycol (PEG) and electrolyte solution would increase ileo‐colonic inflow and stimulate colonic motility. We aimed to investigate the colonic response to distension by oral PEG electrolyte in healthy volunteers (HVs) and to evaluate the effect of single 2 L vs split (2 × 1 L) dosing.

Effects of Bolus and Continuous Nasogastric Feeding on Gastric Emptying, Small Bowel Water Content, Superior Mesenteric Artery Blood Flow, and Plasma Hormone Concentrations in Healthy Adults: A Randomized Crossover Study.

Objective:We aimed to demonstrate the effect of continuous or bolus nasogastric feeding on gastric emptying, small bowel water content, and splanchnic blood flow measured by magnetic resonance imaging (MRI) in the context of changes in plasma gastrointestinal hormone secretion. Background:Nasogastric/nasoenteral tube feeding is often complicated by diarrhea but the contribution of feeding strategy to the etiology is unclear. Methods:Twelve healthy adult male participants who underwent nasogastric intubation before a baseline MRI scan, received 400 mL of Resource Energy (Nestle) as a bolus over 5 minutes or continuously over 4 hours via pump in this randomized crossover study. Changes in gastric volume, small bowel water content, and superior mesenteric artery blood flow and velocity were measured over 4 hours using MRI and blood glucose and plasma concentrations of insulin, peptide YY, and ghrelin were assayed every 30 minutes. Results:Bolus nasogastric feeding led to significant elevations in gastric volume (P < 0.0001), superior mesenteric artery blood flow (P < 0.0001), and velocity (P = 0.0011) compared with continuous feeding. Both types of feeding reduced small bowel water content, although there was an increase in small bowel water content with bolus feeding after 90 minutes (P < 0.0068). Similarly, both types of feeding led to a fall in plasma ghrelin concentration although this fall was greater with bolus feeding (P < 0.0001). Bolus feeding also led to an increase in concentrations of insulin (P = 0.0024) and peptide YY (P < 0.0001), not seen with continuous feeding. Conclusion:Continuous nasogastric feeding does not increase small bowel water content, thus fluid flux within the small bowel is not a major contributor to the etiology of tube feeding-related diarrhea.

Colon wall motility: comparison of novel quantitative semi‐automatic measurements using cine MRI

Recently, cine magnetic resonance imaging (MRI) has shown promise for visualizing movement of the colonic wall, although assessment of data has been subjective and observer dependent. This study aimed to develop an objective and semi‐automatic imaging metric of ascending colonic wall movement, using image registration techniques.

Aerated drinks increase gastric volume and reduce appetite as assessed by MRI: a randomized, balanced, crossover trial

BACKGROUND Compared with nonaerated, isocaloric controls, aerated foods can reduce appetite throughout an entire dieting day. Increased gastric volumes and delayed emptying are possible but unexplored mechanisms. OBJECTIVE We tested the hypothesis that aerated drinks (foams) of differing gastric stability would increase gastric distension and reduce appetite compared with a control drink. DESIGN In a randomized, balanced, crossover trial, 18 healthy male participants consumed the following 3 skimmed-milk-based test products (all 110 kcal): 2 drinks aerated to foams by whipping (to 490 mL), one drink that was stable in the stomach [stable foam (SF)], and one drink that was less stable in the stomach [less-stable foam (LSF)], and a nonaerated drink [liquid control (LC); 140 mL]. Over 4 h, stomach contents (foam, air, and liquid) were imaged using magnetic resonance imaging (MRI), and self-reported appetite ratings were collected and quantified by the area under the curve or time to return to baseline (TTRTB). RESULTS Compared with the LC, both foams caused significantly increased gastric volumes and reduced hunger (all P < 0.001). Compared with the LSF, SF further produced a significantly slower decrease in the total gastric content (P < 0.05) and foam volume (P < 0.0001) and a longer TTRTB (197 compared with 248 min, respectively; P < 0.05), although the hunger AUC was not statistically different. Results for other appetite scales were similar. CONCLUSIONS With this MRI trial, we provide novel insights on the gastrointestinal behavior of aerated drinks by measuring separate volumes of foam, liquid, and air layers in the stomach. Appetite suppression induced by foams could largely be explained by effects on gastric volumes and emptying, which may be further enhanced by foam stability. This trial was registered at clinicaltrials.gov as NCT01690182.

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. DESIGN 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.

OC-090 Different effects of FODMAP (fermentable oligo-, di-, and mono-saccharides, and polyols) components on small bowel water content: an MRI study

Introduction A randomised placebo controlled trial (RCT) has shown that FODMAPs exacerbate irritable bowel syndrome (IBS) symptoms in selected patients. FODMAPs are heterogeneous chemically, the major components being fructose and fructans. Both are poorly absorbed in the small bowel but fructose exerts a much greater osmotic effect than fructans which are fructose polymers. Whether this alters the overall impact is unknown. This study aims to test the hypotheses that (a) fructose will increase small bowel water content (SBWC) more than fructans; (b) adding glucose to fructose will reduce its effect, and (c) fructans will exert most of their effect as a result of colonic fermentation. Methods 4-way, randomised, single blind, crossover study. 16 healthy volunteers underwent abdominal scans in a 1.5T MRI scanner after an overnight fast. They were then fed 500 ml of water containing 40 g glucose, fructose, fructan or 40 g glucose plus 40 g fructose and underwent scanning and breath H2 measurement and completed bowel symptom questionnaires at hourly intervals for 5 h. SBWC was measured from heavily T2 weighted magnetic resonance scans. 1-way analysis of variance was used. Results (Mean±SEM) All drinks were well tolerated with only minor symptoms of gas, bloating, abdominal pain and diarrhoea reported. Relative to glucose, fructose increased SBWC significantly (184±35 ml vs 118±24 ml glucose, p=0.001), while fructans had little effect (SBWC=119±23 ml, p=0.7 vs glucose). Adding 40 g glucose to 40 g fructose decreased SBWC (145±27 ml, but the difference was not significant, p=0.08 vs fructose). Breath H2 was initially higher for fructose than the other three solutions. (AUC was 8959±1880 ppm.min) with fructans having the largest AUC at 14 987±2568 ppm.min). Values returned to baseline for fructose over the 5 h study, but increased to a maximum for fructan after 300 min. Glucose had no effect on breath H2 concentration, but adding an equivalent amount to fructose significantly reduced breath H2 relative to fructose alone (p=0.0006). Conclusion FODMAPs exert a variety of GI responses. Fructose but not fructans increases SBWC relative to glucose. Both fructose and fructans are malabsorbed as confirmed by breath H2 measurements. Fructose malabsorption is significantly reduced by addition of glucose. These different gastrointestinal responses can be readily identified using our non-invasive MRI techniques. Competing interests None declared.

Insights Into the Different Effects of Food on Intestinal Secretion Using Magnetic Resonance Imaging

BACKGROUND Plant foods may stimulate intestinal secretion through chemicals designed to deter herbivores, including lactucins in lettuce and rhein in rhubarb. This may increase ileostomy output and induce diarrhoea in people with intact bowels. OBJECTIVE We aimed to determine the effect of food on intestinal water content using Magnetic Resonance Imaging (MRI). DESIGN A three period crossover trial of isocaloric meals in adults without bowel disorders. Meals: 2 slices white bread with 10 g butter; 300 g rhubarb with 60 mL lactose free cream; 300 g lettuce with 30 mL mayonnaise. PRIMARY OUTCOME Area under curve (AUC) small bowel water content (SBWC) using MRI. SECONDARY OUTCOMES ascending colon water content; T1 relaxation time of ascending colon (T1AC); gastric volume; visual analogue scales of bloating and satiety (0-100). MRI analysts were blinded. Scanned fasting and hourly to 180 min postprandial. Symptoms scored half-hourly. RESULTS 9 female and 6 male subjects completed the study. AUC SBWC fell after bread but rose after lettuce and even more after rhubarb, difference from baseline being (Bread AUC -5662 (1209) ml.min vs Lettuce 3194 (1574) ml.min and Rhubarb 10586 (1629) ml.min (P < 0.01). Rhubarb induced a rise in T1AC but differences at 3 hours were not significant (P = 0.06). Gastric volume at T = 0 significantly was higher for both lettuce and rhubarb (571 ± 92 and 558 ± 89 mls) respectively compared to bread (314 ± 108 mls) (p < 0.0001). Symptom scores were higher for lettuce > rhubarb > bread. CONCLUSION Lettuce and rhubarb meals increased intestinal water content, demonstrating how different foods can alter ileal flow and stool consistency.

OC-068 Measuring the Effect of Ispaghula on Gut Content and Function Using MRI

Introduction Ispaghula husk (IS) is believed to modulate functional gastrointestinal symptoms by drawing water into the bowel to soften stool and accelerate transit, and by adding bulk. It is not thought to be readily fermented. Magnetic Resonance Imaging (MRI) can assess gastrointestinal content and function. The aim of the study was to assess whether MRI could detect and quantify the effects of IS in patients with chronic constipation. Methods A double-blind crossover study in adults with functional constipation or constipation-predominant irritable bowel syndrome. Intervention: Metamucil Original Coarse Fibre® (P&G, USA) 14 g tds – daily IS dose 21 g. Placebo: Maltodextrin(MD) 14 g tds. On day 5 subjects swallowed 5 gadolinium filled capsules. On day 6 MRI scans were taken fasting and hourly for 7 hours while subjects ingested a rice pudding meal and treatment (IS or MD). Whole gut transit was assessed by the weighted average position score of the capsules 24 hours after ingestion (WAPS). Free water in the small bowel (SBWC) and ascending colon (ACWC) was measured as were T1 and T2 relaxation times in the ascending and descending colon (AC & DC), colonic volume and gas.Abstract OC-068 Figure 1 Results 16 subjects completed both treatments. Transit was faster after IS with a mean decrease in WAPS of 24% (p = 0.05, 1 tailed). Postprandial SBWC was markedly higher on IS (p < 0.001) with smaller increases seen in ACWC (p < 0.05). Fasting T1 was significantly higher after IS in both AC and DC. T2 fasting values were also higher. A postprandial rise was seen in both T1AC and T2AC after IS but not MD. Fasting colonic volume increased on PS by mean 332 mL or 48%. Exploratory analysis of colonic gas found that after IS significantly more was detectable both fasting (p < 0.05) and postprandially (p < 0.05). AC gas did not increase until 240 min after PS while transverse colon gas increased steadily through the day.Abstract OC-068 Table 1 Maltodextrin Ispaghula Mean difference(95% confidence interval) WAPS 3.4 (1.6–4.8) 2.2 (1.5–3.0) 0.8 (-0.2–1.7) Colonic Volume (mL) 690 (±55) 1022 (±60) 332 (213–451) T1AC (ms) 596 (±61) 829 (±98) 234 (15–453) T1DC (ms) 366 (±67) 613 (±94) 247 (82–411) Conclusion MRI parameters demonstrated accelerated in transit, increased intestinal water content and increasedcolonic volume with IS. Fasting T1 appears to discriminate constipation from health and responded to treatment. More colonic gas was detected with IS. This may reflect fermentation of IS or interference with small bowel absorption leading to malabsorption of carbohydrate in the rice meal. These novel findings illustrate the potential for MRI to provide insights into the in vivo effects and mechanisms of action of gut modulators. Disclosure of Interest None Declared