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BACKGROUND Current investigations of gastric emptying rarely identify the cause of symptoms or provide a definitive diagnosis in patients with dyspepsia. This study assessed gastric function by magnetic resonance imaging (MRI) using the modular "Nottingham test meal" (NTM) in healthy volunteers (HVs). METHODS The NTM comprises (a) 400 mL liquid nutrient (0.75 kcal/mL) labeled with Gadolinium-DOTA and (b) an optional solid component (12 agar-beads [0 kcal]). Filling sensations were documented. MRI measurements of gastric volume, emptying, contraction wave frequency, and secretion were obtained using validated methods. KEY RESULTS Gastric function was measured in a population of 73 HVs stratified for age and sex. NTM induced moderate satiety and fullness. Labeled fluid was observed in the small bowel in all subjects after meal ingestion ("early-phase" GE). Secretion was rapid such that postprandial gastric content volume was often greater than meal volume (GCV0 > 400 mL), and there was increasing dilution of the meal during the study (P < 0.001). Gastric half-time was median 66-minutes (95% reference interval 35 to 161-minutes ["late-phase" GE]). The number of intact agar beads in the stomach was 7/12 (58%) at 60-minutes and 1/12 (8%) at 120-minutes. Age, bodyweight and sex had measurable effects on gastric function; however, these were small compared to inter-individual variation for most metrics. CONCLUSIONS AND INFERENCES Reference intervals are presented for MRI measurements of gastric function assessed for the mixed liquid/solid NTM. Studies in patients will determine which metrics are of clinical value and also whether the reference intervals presented here offer optimal diagnostic sensitivity and specificity.

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 are often anxious and stressed and stress accelerates small bowel transit which may exacerbate malabsorption. Objective: In this study we investigated the effect of intravenous injection of corticotrophin releasing factor (CRF) on fructose malabsorption and the resulting volume of water in the small bowel. Design: We performed a randomised, placebo controlled, cross-over study of CRF versus 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 Magnetic Resonance imaging (MRI) and breath hydrogen measurement. Orocaecal transit was assessed using the lactose-ureide C13 breath test and the adrenal response to CRF assessed by serial salivary cortisol measurements. Results: (Mean ± SD) CRF injection caused a significant rise in salivary cortisol which lasted 135 minutes. Small bowel water content (SBWC) rose from baseline, peaking at 45 minutes after fructose ingestion while breath hydrogen peaked later at 75 minutes. The area under the curve (AUC) for SBWC from -15 - 135 minutes was significantly lower after CRF versus saline (mean difference [95% CI] 7433 [275, 14591] mL.min, P = 0.04). Ascending colon volume rose after CRF, significantly more for male volunteers than female (P = 0.025). 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

Background 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. Methods Cine balanced turbo field echo MRI images of ascending colonic motility were acquired over 2 min from 23 healthy volunteers (HVs) at baseline and following two different macrogol stimulus drinks (11 HVs drank 1 L and 12 HVs drank 2 L). Motility metrics derived from large scale geometric and small scale pixel movement parameters following image registration were developed using the post ingestion data and compared to observer grading of wall motion. Inter and intra-observer variability in the highest correlating metric was assessed using Bland–Altman analysis calculated from two separate observations on a subset of data. Key Results All the metrics tested showed significant correlation with the observer rating scores. Line analysis (LA) produced the highest correlation coefficient of 0.74 (95% CI: 0.55–0.86), p < 0.001 (Spearman Rho). Bland–Altman analysis of the inter- and intra-observer variability for the LA metric, showed almost zero bias and small limits of agreement between observations (−0.039 to 0.052 intra-observer and −0.051 to 0.054 inter-observer, range of measurement 0–0.353). Conclusions & Inferences The LA index of colonic motility derived from cine MRI registered data provides a quick, accurate and non-invasive method to detect wall motion within the ascending colon following a colonic stimulus in the form of a macrogol drink.

OBJECTIVES: Non-invasive biomarkers which identify different mechanisms of disease in subgroups of irritable bowel syndrome (IBS) could be valuable. Our aim was to seek useful magnetic resonance imaging (MRI) parameters that could distinguish each IBS subtypes. METHODS: 34 healthy volunteers (HV), 30 IBS with diarrhea (IBS-D), 16 IBS with constipation (IBS-C), and 11 IBS with mixed bowel habit (IBS-M) underwent whole-gut transit and small and large bowel volumes assessment with MRI scans from t=0 to t=360 min. Since the bowel frequency for IBS-M were similar to IBS-D, IBS-M and IBS-D were grouped together and labeled as IBS non-constipation group (IBS-nonC). RESULTS: Median (interquartile range): fasting small bowel water content in IBS-nonC was 21 (10–42), significantly less than HV at 44 ml (15–70), P<0.01 as was the postprandial area under the curve (AUC) P<0.01. The fasting transverse colon volumes in IBS-C were significantly larger at 253 (200–329) compared with HV, IBS-nonC whose values were 165 (117–255) and 198 (106–270) ml, respectively, P=0.02. Whole-gut transit time for IBS-C was prolonged at 69 (51–111), compared with HV at 34 (4–63) and IBS-D at 34 (17–78) h, P=0.03. Bloating score (VAS 0–10 cm) correlated with transverse colon volume at t=405 min, Spearman r=0.21, P=0.04. CONCLUSIONS: The constricted small bowel in IBS-nonC and the dilated transverse colon in IBS-C point to significant differences in underlying mechanisms of disease.

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 (H 2) 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, signifi cantly greater than glucose and glucose + fructose (both P < 0.05). Breath H 2 rose more with inulin than with fructose. Glucose when combined with fructose signifi cantly reduced breath H 2 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.

Objective: To study whether maternal cigarette smoking during pregnancy is associated with alterations in the growth of fetal lungs, kidneys, liver, brain, and placenta. Design: A case-control study, with operators performing the image analysis blinded. Setting: Study performed on a research-dedicated magnetic resonance imaging (MRI) scanner (1.5 T) with participants recruited from a large teaching hospital in the United Kingdom. Participants: A total of 26 pregnant women (13 current smokers, 13 non smokers) were recruited; 18 women (10 current smokers, 8 nonsmokers) returned for the second scan later in their pregnancy. Methods: Each fetus was scanned with MRI at 22–27 weeks and 33–38 weeks gestational age (GA). Main outcome measures: Images obtained with MRI were used to measure volumes of the fetal brain, kidneys, lungs, liver and overall fetal size, as well as placental volumes. Results: Exposed fetuses showed lower brain volumes, kidney volumes, and total fetal volumes, with this effect being greater at visit 2 than at visit 1 for brain and kidney volumes, and greater at visit 1 than at visit 2 for total fetal volume. Exposed fetuses also demonstrated lower lung volume and placental volume, and this effect was similar at both visits. No difference was found between the exposed and nonexposed fetuses with regards to liver volume. Conclusion: Magnetic resonance imaging has been used to show that maternal smoking is associated with reduced growth of fetal brain, lung and kidney; this effect persists even when the volumes are corrected for maternal education, gestational age, and fetal sex. As expected, the fetuses exposed to maternal smoking are smaller in size. Similarly, placental volumes are smaller in smoking versus nonsmoking pregnant women.

OBJECTIVES: Non-invasive biomarkers which identify different mechanisms of disease in subgroups of irritable bowel syndrome (IBS) could be valuable. Our aim was to seek useful magnetic resonance imaging (MRI) parameters that could distinguish each IBS subtypes. METHODS: 34 healthy volunteers (HV), 30 IBS with diarrhea (IBS-D), 16 IBS with constipation (IBS-C), and 11 IBS with mixed bowel habit (IBS-M) underwent whole-gut transit and small and large bowel volumes assessment with MRI scans from t=0 to t=360 min. Since the bowel frequency for IBS-M were similar to IBS-D, IBS-M and IBS-D were grouped together and labeled as IBS non-constipation group (IBS-nonC). RESULTS: Median (interquartile range): fasting small bowel water content in IBS-nonC was 21 (10–42), significantly less than HV at 44 ml (15–70), P<0.01 as was the postprandial area under the curve (AUC) P<0.01. The fasting transverse colon volumes in IBS-C were significantly larger at 253 (200–329) compared with HV, IBS-nonC whose values were 165 (117–255) and 198 (106–270) ml, respectively, P=0.02. Whole-gut transit time for IBS-C was prolonged at 69 (51–111), compared with HV at 34 (4–63) and IBS-D at 34 (17–78) h, P=0.03. Bloating score (VAS 0–10 cm) correlated with transverse colon volume at t=405 min, Spearman r=0.21, P=0.04. CONCLUSIONS: The constricted small bowel in IBS-nonC and the dilated transverse colon in IBS-C point to significant differences in underlying mechanisms of disease.

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 are often anxious and stressed and stress accelerates small bowel transit which may exacerbate malabsorption. Objective: In this study we investigated the effect of intravenous injection of corticotrophin releasing factor (CRF) on fructose malabsorption and the resulting volume of water in the small bowel. Design: We performed a randomised, placebo controlled, cross-over study of CRF versus 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 Magnetic Resonance imaging (MRI) and breath hydrogen measurement. Orocaecal transit was assessed using the lactose-ureide C13 breath test and the adrenal response to CRF assessed by serial salivary cortisol measurements. Results: (Mean ± SD) CRF injection caused a significant rise in salivary cortisol which lasted 135 minutes. Small bowel water content (SBWC) rose from baseline, peaking at 45 minutes after fructose ingestion while breath hydrogen peaked later at 75 minutes. The area under the curve (AUC) for SBWC from -15 - 135 minutes was significantly lower after CRF versus saline (mean difference [95% CI] 7433 [275, 14591] mL.min, P = 0.04). Ascending colon volume rose after CRF, significantly more for male volunteers than female (P = 0.025). 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

Background 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. Methods Cine balanced turbo field echo MRI images of ascending colonic motility were acquired over 2 min from 23 healthy volunteers (HVs) at baseline and following two different macrogol stimulus drinks (11 HVs drank 1 L and 12 HVs drank 2 L). Motility metrics derived from large scale geometric and small scale pixel movement parameters following image registration were developed using the post ingestion data and compared to observer grading of wall motion. Inter and intra-observer variability in the highest correlating metric was assessed using Bland–Altman analysis calculated from two separate observations on a subset of data. Key Results All the metrics tested showed significant correlation with the observer rating scores. Line analysis (LA) produced the highest correlation coefficient of 0.74 (95% CI: 0.55–0.86), p < 0.001 (Spearman Rho). Bland–Altman analysis of the inter- and intra-observer variability for the LA metric, showed almost zero bias and small limits of agreement between observations (−0.039 to 0.052 intra-observer and −0.051 to 0.054 inter-observer, range of measurement 0–0.353). Conclusions & Inferences The LA index of colonic motility derived from cine MRI registered data provides a quick, accurate and non-invasive method to detect wall motion within the ascending colon following a colonic stimulus in the form of a macrogol drink.

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 (H 2) 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, signifi cantly greater than glucose and glucose + fructose (both P < 0.05). Breath H 2 rose more with inulin than with fructose. Glucose when combined with fructose signifi cantly reduced breath H 2 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.

Objective: To study whether maternal cigarette smoking during pregnancy is associated with alterations in the growth of fetal lungs, kidneys, liver, brain, and placenta. Design: A case-control study, with operators performing the image analysis blinded. Setting: Study performed on a research-dedicated magnetic resonance imaging (MRI) scanner (1.5 T) with participants recruited from a large teaching hospital in the United Kingdom. Participants: A total of 26 pregnant women (13 current smokers, 13 non smokers) were recruited; 18 women (10 current smokers, 8 nonsmokers) returned for the second scan later in their pregnancy. Methods: Each fetus was scanned with MRI at 22–27 weeks and 33–38 weeks gestational age (GA). Main outcome measures: Images obtained with MRI were used to measure volumes of the fetal brain, kidneys, lungs, liver and overall fetal size, as well as placental volumes. Results: Exposed fetuses showed lower brain volumes, kidney volumes, and total fetal volumes, with this effect being greater at visit 2 than at visit 1 for brain and kidney volumes, and greater at visit 1 than at visit 2 for total fetal volume. Exposed fetuses also demonstrated lower lung volume and placental volume, and this effect was similar at both visits. No difference was found between the exposed and nonexposed fetuses with regards to liver volume. Conclusion: Magnetic resonance imaging has been used to show that maternal smoking is associated with reduced growth of fetal brain, lung and kidney; this effect persists even when the volumes are corrected for maternal education, gestational age, and fetal sex. As expected, the fetuses exposed to maternal smoking are smaller in size. Similarly, placental volumes are smaller in smoking versus nonsmoking pregnant women.

OBJECTIVES: Non-invasive biomarkers which identify different mechanisms of disease in subgroups of irritable bowel syndrome (IBS) could be valuable. Our aim was to seek useful magnetic resonance imaging (MRI) parameters that could distinguish each IBS subtypes. METHODS: 34 healthy volunteers (HV), 30 IBS with diarrhea (IBS-D), 16 IBS with constipation (IBS-C), and 11 IBS with mixed bowel habit (IBS-M) underwent whole-gut transit and small and large bowel volumes assessment with MRI scans from t=0 to t=360 min. Since the bowel frequency for IBS-M were similar to IBS-D, IBS-M and IBS-D were grouped together and labeled as IBS non-constipation group (IBS-nonC). RESULTS: Median (interquartile range): fasting small bowel water content in IBS-nonC was 21 (10–42), significantly less than HV at 44 ml (15–70), P<0.01 as was the postprandial area under the curve (AUC) P<0.01. The fasting transverse colon volumes in IBS-C were significantly larger at 253 (200–329) compared with HV, IBS-nonC whose values were 165 (117–255) and 198 (106–270) ml, respectively, P=0.02. Whole-gut transit time for IBS-C was prolonged at 69 (51–111), compared with HV at 34 (4–63) and IBS-D at 34 (17–78) h, P=0.03. Bloating score (VAS 0–10 cm) correlated with transverse colon volume at t=405 min, Spearman r=0.21, P=0.04. CONCLUSIONS: The constricted small bowel in IBS-nonC and the dilated transverse colon in IBS-C point to significant differences in underlying mechanisms of disease.

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 are often anxious and stressed and stress accelerates small bowel transit which may exacerbate malabsorption. Objective: In this study we investigated the effect of intravenous injection of corticotrophin releasing factor (CRF) on fructose malabsorption and the resulting volume of water in the small bowel. Design: We performed a randomised, placebo controlled, cross-over study of CRF versus 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 Magnetic Resonance imaging (MRI) and breath hydrogen measurement. Orocaecal transit was assessed using the lactose-ureide C13 breath test and the adrenal response to CRF assessed by serial salivary cortisol measurements. Results: (Mean ± SD) CRF injection caused a significant rise in salivary cortisol which lasted 135 minutes. Small bowel water content (SBWC) rose from baseline, peaking at 45 minutes after fructose ingestion while breath hydrogen peaked later at 75 minutes. The area under the curve (AUC) for SBWC from -15 - 135 minutes was significantly lower after CRF versus saline (mean difference [95% CI] 7433 [275, 14591] mL.min, P = 0.04). Ascending colon volume rose after CRF, significantly more for male volunteers than female (P = 0.025). 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

Background 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. Methods Cine balanced turbo field echo MRI images of ascending colonic motility were acquired over 2 min from 23 healthy volunteers (HVs) at baseline and following two different macrogol stimulus drinks (11 HVs drank 1 L and 12 HVs drank 2 L). Motility metrics derived from large scale geometric and small scale pixel movement parameters following image registration were developed using the post ingestion data and compared to observer grading of wall motion. Inter and intra-observer variability in the highest correlating metric was assessed using Bland–Altman analysis calculated from two separate observations on a subset of data. Key Results All the metrics tested showed significant correlation with the observer rating scores. Line analysis (LA) produced the highest correlation coefficient of 0.74 (95% CI: 0.55–0.86), p < 0.001 (Spearman Rho). Bland–Altman analysis of the inter- and intra-observer variability for the LA metric, showed almost zero bias and small limits of agreement between observations (−0.039 to 0.052 intra-observer and −0.051 to 0.054 inter-observer, range of measurement 0–0.353). Conclusions & Inferences The LA index of colonic motility derived from cine MRI registered data provides a quick, accurate and non-invasive method to detect wall motion within the ascending colon following a colonic stimulus in the form of a macrogol drink.

Background Coeliac disease is an autoimmune disease affecting primarily the small bowel mucosa. Diagnosis is by blood test and duodenal biopsy, with the patient on a gluten-containing diet. The only treatment currently available is a gluten free diet (GFD). Further work is required to understand macroscopic gastrointestinal (GI) function and mechanisms of symptoms in coeliac disease. Magnetic Resonance Imaging (MRI) offers a unique tool to study GI fluid volumes, organ volumes and gut transit non-invasively. Objectives This study aimed to test the main hypotheses that: In adults newly diagnosed with coeliac disease, treatment with a GFD will reduce the water content of the fasting small bowel, the volume of the fasting colon and whole gut transit time (WGTT). This work also validated a new method for calibrating small bowel water content (SBWC) measurement on different MRI scanners. Methods 36 newly diagnosed patients and 36 healthy controls were recruited. They attended for an MRI visit having fasted overnight. SBWC, colonic volumes and WGTT were measured. Symptoms, expired breath hydrogen, stool diaries and stool samples were also collected. This was then repeated at 12 months follow-up. A validation study in healthy volunteers was carried out to calibrate and optimise the MRI scanner measurement of SBWC. Results No significant difference in SBWC was seen for the coeliac patients between baseline and 12 month follow up although there was significant difference in fluid volumes compared to the controls. Significant reductions were seen in the overall colonic volumes, and the ascending colon volumes in coeliac patients after treatment with a GFD. Ascending colon volumes and overall colonic volume were also larger in coeliac patients than in the controls both before and after treatment initiation with a GFD. A significant decrease in whole gut transit time was seen in coeliac patients between baseline and 12 month follow up. Transit time between coeliac patients and

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 (H 2) 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, signifi cantly greater than glucose and glucose + fructose (both P < 0.05). Breath H 2 rose more with inulin than with fructose. Glucose when combined with fructose signifi cantly reduced breath H 2 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.

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 are often anxious and stressed and stress accelerates small bowel transit which may exacerbate malabsorption. Objective: In this study we investigated the effect of intravenous injection of corticotrophin releasing factor (CRF) on fructose malabsorption and the resulting volume of water in the small bowel. Design: We performed a randomised, placebo controlled, cross-over study of CRF versus 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 Magnetic Resonance imaging (MRI) and breath hydrogen measurement. Orocaecal transit was assessed using the lactose-ureide C13 breath test and the adrenal response to CRF assessed by serial salivary cortisol measurements. Results: (Mean ± SD) CRF injection caused a significant rise in salivary cortisol which lasted 135 minutes. Small bowel water content (SBWC) rose from baseline, peaking at 45 minutes after fructose ingestion while breath hydrogen peaked later at 75 minutes. The area under the curve (AUC) for SBWC from -15 - 135 minutes was significantly lower after CRF versus saline (mean difference [95% CI] 7433 [275, 14591] mL.min, P = 0.04). Ascending colon volume rose after CRF, significantly more for male volunteers than female (P = 0.025). 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