Effect of experimental stress on the small bowel and colon in healthy humans.

BACKGROUND: Symptoms of irritable bowel syndrome (IBS) are frequently reported to be exacerbated by stress. Animal studies suggest that corticotrophin releasing hormone (CRH) mediates the effect of stress on the bowel. We have shown that stressed IBS patients with diarrhea have constricted small bowels. We hypothesized that we could mimic this effect by applying experimental stress in the form of either hand immersion in ice water or CRH injection in healthy volunteers (HV). METHODS: The postprandial effect of the cold pressor test (repeated hand immersion in ice cold water) and injection of CRH, were assessed vs control in two groups of 18 HVs. KEY RESULTS: CRH produced a significant rise from baseline salivary cortisol levels (p = 0.004) not seen with the cold pressor test. Small bowel water content (SBWC) fell postprandially on all four treatments. SBWC was significantly reduced by both stressors but CRH caused a greater effect (anova, p < 0.003 vs p = 0.02). Ascending colon (AC) volume was greater after CRH injection compared with saline (p = 0.002) but no differences were seen with the cold pressor test vs warm water. Postprandial increase in colon volume was also reduced by CRH which also increased the sensations of distension and bloating. CONCLUSIONS & INFERENCES: Two experimental stressors were shown to constrict the small bowel, mimicking the effect previously seen in IBS-D patients. CRH increased the volume of the AC. We speculate that stress accelerates transfer of water from the small bowel to the AC.

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

BACKGROUND: 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. METHODS: Twelve HVs received a split dose (1 L the evening before and 1 L on the study day) and another 12 HVs a single dose (2 L on the main study day) of PEG electrolyte. They underwent MRI scans, completed symptom questionnaires, and provided stool samples. Outcomes included small bowel water content, ascending colon motility index, and regional colonic volumes. KEY RESULTS: Small bowel water content increased fourfold from baseline after ingesting both split (p = 0.0010) and single dose (p = 0.0005). The total colonic volume increase from baseline was smaller for the split dose at 35 ± 8% than for the single dose at 102 ± 27%, p = 0.0332. The ascending colon motility index after treatment was twofold higher for the single dose group (p = 0.0103). CONCLUSIONS & INFERENCES: Ingestion of 1 and 2 L PEG electrolyte solution caused a rapid increase in the small bowel and colonic volumes and a robust rise in colonic motility. The increase in both volumes and motility was dose dependent. Such a challenge, being well-tolerated, could be a useful way of assessing colonic motility in future studies.

Fasting and postprandial volumes of the undisturbed colon: normal values and changes in diarrhea-predominant irritable bowel syndrome measured using serial MRI.

BACKGROUND: Previous assessments of colon morphology have relied on tests which were either invasive or used ionizing radiation. We aimed to measure regional volumes of the undisturbed colon in healthy volunteers (HV) and patients with diarrhea-predominant irritable bowel syndrome (IBS-D). METHODS: 3D regional (ascending, transverse, and descending) colon volumes were measured in fasting abdominal magnetic resonance (MR) images of 75 HVs and 25 IBS-D patients. Thirty-five of the HV and all 25 IBS-D subjects were fed a standard meal and postprandial MRI data obtained over 225 min. KEY RESULTS: Colonic regions were identified and 3D maps from cecum to sigmoid flexure were defined. Fasted regional volumes showed wide variation in both HVs being (mean ± SD) ascending colon (AC) 203 ± 75 mL, transverse (TC) 198 ± 79 mL, and descending (DC) 160 ± 86 mL with no difference from IBS-D subjects (AC 205 ± 69 mL, TC 232 ± 100 mL, and DC 151 ± 71 mL, respectively). The AC volume expanded by 10% after feeding (p = 0.007) in the 35 HV possibly due to increased ileo-colonic inflow. A later rise in AC volume occurred from t = 90 to t = 240 min as the meal residue entered the cecum. In contrast, IBS-D subjects showed a much reduced postprandial response of the AC (p < 0.0001) and a greater increase in TC volume after 90 min (p = 0.0244) compared to HV. CONCLUSIONS & INFERENCES: We have defined a normal range of the regional volumes of the undisturbed colon in fasted and fed states. The AC in IBS-D appeared less able to accommodate postprandial inflow which may account for faster colonic transit.

The effects of loperamide, or loperamide plus simethicone, on the distribution of gut water as assessed by MRI in a mannitol model of secretory diarrhoea.

BACKGROUND: Loperamide (LOP) is an anti-diarrhoeal agent which is thought to act largely by slowing transit with an uncertain effect on the fluid content of the small and large bowel in humans. Adding simethicone (SIM) to LOP improves its efficacy, but the mechanism of interaction is unclear. Novel MRI techniques to assess small bowel water content (SBWC) have shown that mannitol solutions markedly increase SBWC and can be used as a model of diarrhoea. AIM: We aimed to use quantitative MRI techniques to compare the actions in the gut of LOP and LOP + SIM in a model of secretory diarrhoea using mannitol. METHODS: A total of 18 healthy volunteers ingested capsules containing placebo (PLA) or 12 mg LOP or 12 mg LOP + 125 mg SIM. After 100 min they were given a drink containing 5% mannitol in 350 mL of water. They underwent baseline fasting and postprandial serial MRI scans at 45 min intervals for 4.5 h after ingesting the drink. A range of MRI sequences was acquired to image the gut. RESULTS: LOP and LOP + SIM significantly accelerated gastric emptying (P < 0.03) and reduced SBWC during the late phase (135-270 min after mannitol ingestion), P < 0.009, while delaying arrival of fluid in the ascending colon (AC). The relaxation time T2 of the contents of the AC was reduced by both drugs (P < 0.0001). CONCLUSIONS: LOP and LOP + SIM accelerate gastric emptying, but reduce small bowel water content which may contribute to the delay in oral-caecal transit and overall anti-diarrhoeal effect.