Mechanisms underlying the laxative effect of lactulose: A randomized placebo-controlled trial showing increased small bowel water and motility unaltered by the 5-HT3 receptor antagonist, ondansetron.

BACKGROUND: Lactulose is a laxative which accelerates transit and softens stool. Our aim was to investigate its mechanism of action and use this model of diarrhea to investigate the anti-diarrheal actions of ondansetron. METHODS: A double-blind, randomized, placebo-controlled crossover study of the effect of ondansetron 8 mg in 16 healthy volunteers. Serial MRI scans were performed fasted and 6 h after a meal. Participants then received lactulose 13.6 g twice daily and study drug for a further 36 h. On Day 3, they had further serial MRI scans for 4 h. Measurements included small bowel water content (SBWC), colonic volume, colonic gas, small bowel motility, whole gut transit, and ascending colon relaxation time (T1AC), a measure of colonic water content. KEY RESULTS: Lactulose increased area under the curve (AUC) of SBWC from 0 to 240 min, mean difference 14.2 L · min (95% CI 4.1, 24.3), p = 0.009, and substantially increased small bowel motility after 4 h (mean (95% CI) 523 (457-646) a.u. to 852 (771-1178) a.u., p = 0.007). There were no changes in T1AC after 36 h treatment. Ondansetron did not significantly alter SBWC, small bowel motility, transit, colonic volumes, colonic gas nor T1AC, with or without lactulose. CONCLUSION & INFERENCES: Lactulose increases SBWC and stimulates small bowel motility; however, unexpectedly it did not significantly alter colonic water content, suggesting its laxative effect is not osmotic but due to stimulation of motility. Ondansetron's lack of effect on intestinal water suggests its anti-diarrheal effect is not due to inhibition of secretion but more likely altered colonic motility.

Psychological and colonic factors in painful diverticulosis.

BACKGROUND: The importance of psychological factors in symptom expression in diverticulosis is unknown. This follow-up study assessed the relative importance of colonic and psychological factors in symptom expression. METHODS: Patients with barium enema-proven diverticula were sent a bowel symptom questionnaire in 1999 and again in 2006 with additional psychological questionnaires included. RESULTS: Some 170 of 261 initial responders were eligible for follow-up and 124 (72.9 per cent) provided complete replies. Forty-two (33.9 per cent) of 124 respondents experienced recurrent abdominal pain a median of 3.5 (interquartile range (i.q.r.) 2.00-9.25) days per month, with a median duration of 1 (i.q.r. 0.7-2) h. Multivariable analysis identified a history of acute diverticulitis (odds ratio 3.98; P = 0.010) and a raised score on the Hospital Anxiety and Depression Scale (odds ratio 2.53; P = 0.030) as the best predictors of recurrent pain. CONCLUSION: Psychological and colonic factors are important in symptom expression in diverticulosis.

Guidelines on the irritable bowel syndrome: mechanisms and practical management.

BACKGROUND: IBS affects 5-11% of the population of most countries. Prevalence peaks in the third and fourth decades, with a female predominance. AIM: To provide a guide for the assessment and management of adult patients with irritable bowel syndrome. METHODS: Members of the Clinical Services Committee of The British Society of Gastroenterology were allocated particular areas to produce review documents. Literature searching included systematic searches using electronic databases such as Pubmed, EMBASE, MEDLINE, Web of Science, and Cochrane databases and extensive personal reference databases. RESULTS: Patients can usefully be classified by predominant bowel habit. Few investigations are needed except when diarrhoea is a prominent feature. Alarm features may warrant further investigation. Adverse psychological features and somatisation are often present. Ascertaining the patients' concerns and explaining symptoms in simple terms improves outcome. IBS is a heterogeneous condition with a range of treatments, each of which benefits a small proportion of patients. Treatment of associated anxiety and depression often improves bowel and other symptoms. Randomised placebo controlled trials show benefit as follows: cognitive behavioural therapy and psychodynamic interpersonal therapy improve coping; hypnotherapy benefits global symptoms in otherwise refractory patients; antispasmodics and tricyclic antidepressants improve pain; ispaghula improves pain and bowel habit; 5-HT(3) antagonists improve global symptoms, diarrhoea, and pain but may rarely cause unexplained colitis; 5-HT(4) agonists improve global symptoms, constipation, and bloating; selective serotonin reuptake inhibitors improve global symptoms. CONCLUSIONS: Better ways of identifying which patients will respond to specific treatments are urgently needed.

Demonstration of differences in colonic volumes, transit, chyme consistency, and response to psyllium between healthy and constipated subjects using magnetic resonance imaging.

BACKGROUND: In functional gastrointestinal disorders a lack of objective biomarkers limits evaluation of underlying mechanisms. We aimed to demonstrate the utility of magnetic resonance imaging for this task using psyllium, an effective constipation treatment, in patients and controls. METHODS: Two crossover studies: (i) adults without constipation (controls, n = 9) took three treatments in randomized order for 6 days - maltodextrin (placebo), psyllium 3.5 g t.d.s and 7 g t.d.s., (ii) adults with chronic constipation (patients, n = 20) took placebo and psyllium 7 g t.d.s. for 6 days. MRI was performed fasting and postprandially on day 6. Measurements included small bowel and ascending colon water content, colonic volume, transit time, and MR relaxometry (T1, T2) to assess colonic chyme. Stool water percentage was measured. RESULTS: 7 g psyllium t.d.s. increased fasting colonic volumes in controls from median 372 mL (IQR 284-601) to 578 mL (IQR 510-882), and in patients from median 831 mL (IQR 745-934) to 1104 mL (847-1316), P < .05. Mean postprandial small bowel water was higher in controls and patients after 7 g psyllium t.d.s. vs placebo. Whole gut transit was slower in patients than controls (P < .05). T1 of the descending colon chyme (fasting) was lower in patients (213 ms, 176-420) than controls (440 ms, 352-884, P < .05) on placebo, but increased by 7 g psyllium t.d.s. (590 ms, 446-1338), P < .001. Descending colon T1 correlated with baseline stool water content and stool frequency on treatment. CONCLUSIONS AND INFERENCES: MRI measurements can objectively demonstrate the mode of action of therapy targeting intestinal fluid content in constipation.

Cortical differences in diverticular disease and correlation with symptom reports.

BACKGROUND: Recent studies have shown that the brain of patients with gastrointestinal disease differ both structurally and functionally from that of controls. Highly somatizing diverticular disease (HSDD) patients were also shown to differ from low somatizing (LSDD) patients functionally. This study aimed to investigate how they differed structurally. METHODS: Four diseases subgroups were studied in a cross-sectional design: 20 patients with asymptomatic diverticular disease (ADD), 18 LSDD, 16 HSDD, and 18 with irritable bowel syndrome. We divided DD patients into LSDD and HSDD using a cutoff of 6 on the Patient Health Questionnaire 12 Somatic Symptom (PHQ12-SS) scale. All patients underwent a 1-mm isotropic structural brain MRI scan and were assessed for somatization, hospital anxiety, depression, and pain catastrophizing. Whole brain volumetry, cortical thickness analysis and voxel-based morphometry were carried out using Freesurfer and SPM. KEY RESULTS: We observed decreases in gray matter density in the left and right dorsolateral prefrontal cortex (dlPFC), and in the mid-cingulate and motor cortex, and increases in the left (19, 20) and right (19, 38) Brodmann Areas. The average cortical thickness differed overall across groups (P = .002) and regionally: HSDD > ADD in the posterior cingulate cortex (P = .03), HSDD > LSDD in the dlPFC (P = .03) and in the ventrolateral PFC (P < .001). The thickness of the anterior cingulate cortex and of the mid-prefrontal cortex were also found to correlate with Pain Catastrophizing (Spearman's ρ = 0.24, P = .043 uncorrected and Spearman's ρ = 0.25, P = .03 uncorrected). CONCLUSION & INFERENCES: This is the first study of structural gray matter abnormalities in diverticular disease patients. The data show brain differences in the pain network.

MRI assessment of the postprandial gastrointestinal motility and peptide response in healthy humans.

BACKGROUND: Feeding triggers inter-related gastrointestinal (GI) motor, peptide and appetite responses. These are rarely studied together due to methodological limitations. Recent MRI advances allow pan-intestinal, non-invasive assessment of motility in the undisturbed gut. This study aimed to develop a methodology to assess pan-intestinal motility and transit in a single session using MRI and compare imaging findings to GI peptide responses to a test meal and symptoms in a healthy volunteer cohort. METHODS: Fifteen healthy volunteers (29.3±2.7 years and BMI 20.1±1.2 kg m-2 ) underwent baseline and postprandial MRI scans, symptom questionnaires, and blood sampling (for subsequent GI peptide analysis, Glucagon-like peptide-1 [GLP-1], Polypeptide YY [PYY], Cholecystokinin [CCK]) at intervals for 270 minutes following a 400 g soup meal (204 kcal, Heinz, UK). Gastric volume, gall bladder volume, small bowel water content, small bowel motility, and whole gut transit were measured from the MRI scans. KEY RESULTS: (mean±SEM) Small bowel motility index increased from fasting 39±3 arbitrary units (a.u.) to a maximum of 87±7 a.u. immediately after feeding. PYY increased from fasting 98±10 pg mL-1 to 149±14 pg mL-1 at 30 minutes and GLP-1 from fasting 15±3 µg mL-1 to 22±4 µg mL-1 . CCK increased from fasting 0.40±0.06 pmol mL-1 to 0.94±0.1 pmol mL-1 . Gastric volumes declined with a T1/2 of 46±5 minute and the gallbladder contracted from a fasting volume of 19±2 mL-1 to 12±2 mL-1 . Small bowel water content increased from 39±2 mL-1 to 51±2 mL-1 postprandial. Fullness VAS score increased from 9±5 mm to 41±6 mm at 30 minutes postprandial. CONCLUSIONS AND INFERENCES: The test meal challenge was effective in inducing a change in MRI motility end-points which will improve understanding of the pathophysiological postprandial GI response.

Recent advances in understanding the role of serotonin in gastrointestinal motility in functional bowel disorders: alterations in 5-HT signalling and metabolism in human disease.

Serotonin (5-hydroxytryptamine, 5-HT) is present in abundance within the gut, most stored in enterochromaffin cell granules. It is released by a range of stimuli, most potently by mucosal stroking. Released 5-HT stimulates local enteric nervous reflexes to initiate secretion and propulsive motility. It also acts on vagal afferents altering motility and in large amounts induces nausea. Rapid reuptake by a specific transporter (serotonin transporter, SERT) limits its diffusion and actions. Abnormally increased 5-HT is found in a range of gastrointestinal disorders including chemotherapy-induced nausea and vomiting, carcinoid syndrome, coeliac disease, inflammatory bowel disease and irritable bowel syndrome (IBS) with diarrhoea (IBS-D), especially that developing following enteric infection. Impaired SERT has been described in IBS-D and might account for some of the increase in mucosal 5-HT availability. 5-HT(3) receptor antagonists inhibit chemotherapy-induced nausea and diarrhoea associated with both carcinoid syndrome and IBS. While IBS-D is associated with increased 5-HT postprandially, IBS with constipation (IBS-C) is associated with impaired 5-HT response and responds to 5-HT(4) agonists such as Prucalopride and 5-HT(4) partial agonists such as Tegaserod.

Mechanisms of hypersensitivity in IBS and functional disorders.

General introduction The concept of visceral hypersensitivity is accepted as being germane to several functional gastrointestinal disorders (FGIDs). The causes or risk factors associated with this hypersensitivity are unclear. This article addresses the proposed mechanisms leading to hypersensitivity: from genetic to inflammatory disorders, from central to peripheral alterations of function. However, in order to place visceral hypersensitivity in a more global perspective as an aetiological factor for FGIDs, it also provides a review of recent evidence regarding the role of other peripheral mechanisms (the intraluminal milieu), as also genetic factors in the pathophysiology of these disorders. The article has been divided into five independent sections. The first three sections summarize the evidence of visceral hypersensitivity as a biological marker of functional gut disorders, the peripheral and central mechanisms involved, and the role of inflammation on hypersensitivity. In opposition to visceral hypersensitivity as an isolated phenomenon in functional gut disorders, the last two sections focus on the importance of peripheral mechanisms, like motor disturbances, specifically those resulting on altered transport of intestinal gas, and alterations of the intraluminal milieu and genetics.

Non-invasive quantification of small bowel water content by MRI: a validation study.

Substantial water fluxes across the small intestine occur during digestion of food, but so far measuring these has required invasive intubation techniques. This paper describes a non-invasive magnetic resonance imaging (MRI) technique for measuring small bowel water content which has been validated using naso-duodenal infusion. Eighteen healthy volunteers were intubated, with the tube position being verified by MRI. After a baseline MRI scan, each volunteer had eight 40 ml boluses of a non-absorbable mannitol and saline solution infused into their proximal small bowel with an MRI scan being acquired after each bolus. The MRI sequence used was an adapted magnetic resonance cholangiopancreatography sequence. The image data were thresholded to allow for intra- and inter-subject signal variations. The MRI measured volumes were then compared to the known infused volumes. This MRI technique gave excellent images of the small bowel, which closely resemble those obtained using conventional radiology with barium contrast. The mean difference between the measured MRI volumes and infused volumes was 2% with a standard deviation of 10%. The maximum 95% limits of agreement between observers were -15% to +17% while measurements by the same operator on separate occasions differed by only 4%. This new technique can now be applied to study alterations in small bowel fluid absorption and secretion due to gastrointestinal disease or drug intervention.

Assessment of motion of colonic contents in the human colon using MRI tagging.

BACKGROUND: We have previously reported a non-invasive, semi-automated technique to assess motility of the wall of the ascending colon (AC) using Magnetic Resonance Imaging. This study investigated the feasibility of using a tagged MRI technique to visualize and assess the degree of flow within the human ascending colon in healthy subjects and those suffering from constipation. METHODS: An open-labeled study of 11 subjects with constipation and 11 subjects without bowel disorders was performed. MRI scans were acquired fasted, then 60 and 120 minutes after ingestion of a 500 mL macrogol preparation. The amount of free fluid in the small and large bowel was assessed using a heavily T2-weighted MRI sequence. The internal movement of the contents of the AC was visualized using a cine tagged MRI sequence and assessed by a novel analysis technique. Comparisons were made between fasting and postprandial scans within individuals, and between the constipation and control groups. KEY RESULTS: Macrogol significantly increased the mobile, MR visible water content of the ascending colon at 60 minutes postingestion compared to fasted data (controls P=.001, constipated group P=.0039). The contents of the AC showed increased motion in healthy subjects but not in the constipated group with significant differences between groups at 60 minutes (P<.002) and 120 minutes (P<.003). CONCLUSIONS AND INFERENCES: This study successfully demonstrated the use of a novel MRI tagging technique to visualize and assess the motion of ascending colon contents following a 500 mL macrogol challenge. Significant differences were demonstrated between healthy and constipated subjects.

Randomised clinical trial: mesalazine versus placebo in the prevention of diverticulitis recurrence.

BACKGROUND: Previous studies have reached conflicting conclusions regarding the efficacy of mesalazine in the prevention of recurrent diverticulitis. AIM: To investigate the efficacy and safety of mesalazine granules in the prevention of recurrence of diverticulitis after acute uncomplicated diverticulitis. METHODS: Two phase 3, randomised, placebo-controlled, double-blind multicentre trials (SAG-37 and SAG-51) investigated mesalazine granules in patients with prior episodes (<6 months) of uncomplicated left-sided diverticulitis. Patients were randomised to receive either 3 g mesalazine once daily or placebo (SAG-37, n=345) or to receive either 1.5 g mesalazine once daily, 3 g once daily or placebo for 96 weeks (SAG-51, n=330). The primary endpoint was the proportion of recurrence-free patients during 48 weeks (SAG-37 and SAG-51) or 96 weeks (SAG-51) of treatment. RESULTS: Mesalazine did not increase the proportion of recurrence-free patients over 48 or 96 weeks compared to placebo. In SAG-37, the proportion of recurrence-free patients during 48 weeks was 67.9% with mesalazine and 74.4% with placebo (P=.226). In SAG-51, the proportion of recurrence-free patients over 48 weeks was 46.0% with 1.5 g mesalazine, 52.0% with 3 g mesalazine and 58.0% with placebo (P=.860 for 3 g mesalazine vs placebo) and over 96 weeks 6.9%, 9.8% and 23.1% respectively (P=.980 for 3 g mesalazine vs placebo). Patients with only one diverticulitis episode in the year prior to study entry had a lower recurrence risk compared to >1 episode. Safety data revealed no new adverse events. CONCLUSION: Mesalazine was not superior to placebo in preventing recurrence of diverticulitis.

Role of motility in chronic diarrhoea.

Patients complaining of 'chronic diarrhoea' usually mean the passage of loose, urgent stools. Chronic diarrhoea is a feature of malabsorption; it may also be seen in the 'dumping syndrome' which follows gastric surgery, small intestinal bacterial overgrowth, bile salt malabsorption and in malabsorption of simple sugars including most commonly lactose, fructose and sorbitol. Excessively rapid entry of chyme into the small or large intestine generates propulsive motor patterns leading to accelerated transit. Inflammation is associated with decreased normal mixing motor patterns but increased propulsive motility including high amplitude propagated contractions (HAPCs). Evidence for abnormal small intestinal motility in the diarrhoea associated with irritable bowel syndrome (IBS) is conflicting and any difference appears small. Increased colonic HAPCs with increased propulsion is seen in IBS with diarrhoea (IBS-D). Stress-induced colonic motility is increased in IBS-D with hyper-responsiveness to corticotrophin releasing factor (CRF). Long-lasting increases in mucosal serotonin availability may contribute to the chronic diarrhoea seen in IBS-D and coeliac disease. Treatments for abnormal motility in chronic diarrhoea include those designed to correct specific underlying abnormalities including octreotide, antibiotics, colestyramine, specific food avoidance and anti-inflammatory agents. There are also treatments aimed primarily at altering motility directly including opiates, 5HT3 receptor antagonists and amitriptyline.

Anticipation of thermal pain in diverticular disease.

BACKGROUND: The relative importance of peripheral nerve injury or central pain processing in painful diverticular disease (DD) is unclear. Functional magnetic resonance imaging (fMRI) has demonstrated that dysfunctional central pain processing predominates in irritable bowel syndrome (IBS). This study aims to identify anticipatory changes in symptomatic DD (SDD) compared to asymptomatic DD (ADD) and IBS patients. METHODS: Gastrointestinal symptoms and somatization were evaluated via the Patient Health Question-12 Somatic Symptom and the SDD group divided into low (≤6 [LSDD]) and high (≥7 [HSDD]) somatization. Cued painful cutaneous thermal stimuli were delivered to the left hand and foot during fMRI. Fixed effect group analysis of the 'cued' anticipatory phase was performed. KEY RESULTS: Within the right posterior insula, greater deactivation was found in the ADD compared to other groups. In emotion processing centers, anterior and middle insula, greater activation was identified in all patient compared to the ADD group, and in LSDD compared to IBS and HSDD groups. In comparison, amygdala deactivation was greater in ADD than the IBS and HSDD groups, and in LSDD vs HSDD groups. Descending nociceptive control centers, such as the superior medial frontal and orbitofrontal cortex, also showed greater deactivation in the ADD and LSDD compared to the HSDD and IBS groups. CONCLUSIONS & INFERENCES: The HSDD group have altered anticipatory responses to thermal pain, similar to IBS group. The LSDD are similar to ADD group. This suggests underlying differences in pain pathophysiology, and the need for individualized treatment strategies to target the cause of their chronic pain.

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

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.

Colonic response to laxative ingestion as assessed by MRI differs in constipated irritable bowel syndrome compared to functional constipation.

BACKGROUND: Functional constipation (FC) and irritable bowel syndrome with constipation (IBS-C) share many symptoms but underlying mechanisms may be different. We have developed a magnetic resonance imaging (MRI) technique to measure intestinal volumes, transit, and motility in response to a laxative, Moviprep(®) . We aim to use these biomarkers to study the pathophysiology in IBS-C and FC. METHODS: Twenty-four FC and 24 IBS-C were studied. Transit was assessed using the weighted average position score (WAPS) of five MRI marker pills, taken 24 h before MRI scanning. Following baseline scan, participants ingested 1 L of Moviprep(®) followed by hourly scans. Magnetic resonance imaging parameters and bowel symptoms were scored from 0 to 4 h. KEY RESULTS: Weighted average position score for FC was 3.6 (2.5-4.2), significantly greater than IBS-C at 2.0 (1.5-3.2), p = 0.01, indicating slower transit for FC. Functional constipation showed greater fasting small bowel water content, 83 (63-142) mL vs 39 (15-70) mL in IBS-C, p < 0.01 and greater ascending colon volume (AC), 314 (101) mL vs 226 (71) mL in IBS-C, p < 0.01. FC motility index was lower at 0.055 (0.044) compared to IBS-C, 0.107 (0.070), p < 0.01. Time to first bowel movement following ingestion of Moviprep(®) was greater for FC, being 295 (116-526) min, compared to IBS-C at 84 (49-111) min, p < 0.01, and correlated with AC volume 2 h after Moviprep(®) , r = 0.44, p < 0.01. Using a cut-off >230 min distinguishes FC from IBS-C with low sensitivity of 55% but high specificity of 95%. CONCLUSION & INFERENCES: Our objective MRI biomarkers allow a distinction between FC and IBS-C.

Pharmacology of dietary fibre.

"Dietary fibre" includes a range of relatively poorly digested food substances mainly composed of non-starch polysaccharides. Pectins and gums are multi-branched hydrophilic substances, forming viscous solutions that delay gastric emptying and nutrient absorption from the small bowel. They are used to delay gastric emptying and improve glycemic control in diabetes, as well as to alleviate constipation. Other fibres, including cellulose and lignins, are insoluble and have little effect on gastric emptying and small bowel transit. They markedly accelerate colonic transit and are frequently used as laxatives. Other important, less well-characterised effects of fibre include lowering of blood cholesterol, increase in satiety and possibly reduction in colon neoplasia.

Enterochromaffin cell hyperplasia and decreased serotonin transporter in a mouse model of postinfectious bowel dysfunction.

Patients with postinfective irritable bowel syndrome and Trichinella spiralis-infected mice share many features including visceral hypersensitivity and disordered motility. We assessed enterochromaffin (EC) numbers and serotonin transporter (SERT) using National Institute of Health (NIH) female mice studied for up to 56 days post-T. spiralis infection. The effects of steroid treatment and the T-cell dependence of the observed responses were assessed by infection of hydrocortisone-treated or T-cell receptor knock out [TCR (betaxdelta) KO] animals. Enterochromaffin cell density in uninfected animals increased from duodenum 10.0 cells mm-2 (5.9-41.0) to colon 61.8. (46.3-162) cells mm-2 P<0.0001. Infection increased duodenal and jejunal counts which rose to 37.3 (22-57.7) cells mm-2 and 50.6 (7-110.8) cells mm-2, respectively, at day 14. Infection significantly reduced jejunal SERT expression, with luminance values falling from 61.0 (45.1-98.3) to a nadir of 11.6 (0-36.0) units at day 9, P<0.001. Specific deficiencies in all T cells reduced EC hyperplasia and abrogated infection-induced mastocytosis. Thus infection induced inflammation increases EC numbers, as has been reported in PI-IBS, and reduces SERT. This may increase mucosal 5HT availability and contribute to the clinical presentation of PI-IBS.

Changing views on diverticular disease: impact of aging, obesity, diet, and microbiota.

The development of colonic diverticulosis is a common aging change in industrialized nations. While most patients have asymptomatic diverticulosis, around one in five develops symptomatic diverticular disease. This is characterized by recurrent abdominal pain and disturbed bowel habit. Some of the pain episodes are prolonged and are due to acute diverticulitis, which itself may be complicated by abscess, perforation, fistulation, or stricture formation. Risk factors favouring the development of symptomatic diverticular disease include obesity, smoking and diets low in fiber but high in red meat and animal fat. What determines the transition from asymptomatic diverticulosis to symptomatic diverticular disease is unclear but neuromuscular changes following acute diverticulitis may be responsible in some cases. The severity of symptoms generated depends on cerebral pain processing which is influenced by psychosocial factors. These are important considerations in deciding optimal patient management. Prior theories of the cause of diverticulosis suggested that constipation was an important cause, but new data challenge this and has provoked new ideas. Underlying mechanisms causing diverticulosis include weakening of the colonic wall and/or degenerative changes in the enteric nerves. Dietary induced changes in microbiota and the host inflammatory response may underlie the subsequent development of acute/chronic diverticulitis and its sequela.

Magnetic resonance imaging to evaluate gastrointestinal function.

Magnetic resonance imaging of gastrointestinal (GI) function has advanced substantially in the last few years. The ability to obtain high resolution images of the undisturbed bowel with tunable tissue contrast and using no ionizing radiation are clear advantages, particularly for children and women of reproductive age. Barriers to diffusion in clinical practice so far include the need to demonstrate clinical value and the burden of data processing. Both difficulties are being addressed and the technique is providing novel insights into both upper and lower GI disorders of function at an ever increasing rate.

Additive effects of gastric volumes and macronutrient composition on the sensation of postprandial fullness in humans.

BACKGROUND/OBJECTIVES: Intake of food or fluid distends the stomach and triggers mechanoreceptors and vagal afferents. Wall stretch and tension produces a feeling of fullness. Duodenal infusion studies assessing gastric sensitivity by barostat have shown that the products of fat digestion have a greater effect on the sensation of fullness and also dyspeptic symptoms than carbohydrates. We tested here the hypothesis that fat and carbohydrate have different effects on gastric sensation under physiological conditions using non-invasive magnetic resonance imaging (MRI) to measure gastric volumes. SUBJECTS/METHODS: Thirteen healthy subjects received a rice pudding test meal with added fat or added carbohydrate on two separate occasions and underwent serial postprandial MRI scans for 4.5 h. Fullness was assessed on a 100-mm visual analogue scale. RESULTS: Gastric half emptying time was significantly slower for the high-carbohydrate meal than for the high-fat meal, P=0.0327. Fullness significantly correlated with gastric volumes for both meals; however, the change from baseline in fullness scores was higher for the high-fat meal for any given change in stomach volume (P=0.0147), despite the lower energy content and faster gastric emptying of the high-fat meal. CONCLUSIONS: Total gastric volume correlates positively and linearly with postprandial fullness and ingestion of a high-fat meal increases this sensation compared with high-carbohydrate meal. These findings can be of clinical interest in patients presenting with postprandial dyspepsia whereby manipulating gastric sensitivity by dietary intervention may help to control digestive sensations.