Giles Major

Irritable bowel syndrome, inflammatory bowel disease and the microbiome.

Purpose of reviewThe review aims to update the reader on current developments in our understanding of how the gut microbiota impact on inflammatory bowel disease and the irritable bowel syndrome. It will also consider current efforts to modulate the microbiota for therapeutic effect. Recent findingsGene polymorphisms associated with inflammatory bowel disease increasingly suggest that interaction with the microbiota drives pathogenesis. This may be through modulation of the immune response, mucosal permeability or the products of microbial metabolism. Similar findings in irritable bowel syndrome have reinforced the role of gut-specific factors in this ‘functional’ disorder. Metagenomic analysis has identified alterations in pathways and interactions with the ecosystem of the microbiome that may not be recognized by taxonomic description alone, particularly in carbohydrate metabolism. Treatments targeted at the microbial stimulus with antibiotics, probiotics or prebiotics have all progressed in the past year. Studies on the long-term effects of treatment on the microbiome suggest that dietary intervention may be needed for prolonged efficacy. SummaryThe microbiome represents ‘the other genome’, and to appreciate its role in health and disease will be as challenging as with our own genome. Intestinal diseases occur at the front line of our interaction with the microbiome and their future treatment will be shaped as we unravel our relationship with it.

IBS and IBD — separate entities or on a spectrum?

The acute phase of IBD with inflamed gut and often ulcerated mucosa is clearly different from the apparently normal mucosa characteristic of IBS. However, more detailed assessment has detected immune activation, increased gut permeability, increased mucosal serotonin availability, abnormalities of enteric nerve structure and function, and dysbiosis in gut microbiota in IBS — all features seen in IBD. Furthermore, as treatments for inflammation in IBD have become more effective it is now apparent that ∼1 in 3 patients with IBD in remission from inflammation still have persistent abnormalities of sensation, motility and gut microbiota, which might cause IBS-like symptoms. This Perspective explores the overlap between IBS and IBD and their treatments, proposing future directions for research in this stimulating area.

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.

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

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.

Effect of bread gluten content on gastrointestinal function: a crossover MRI study on healthy humans

Gluten is a crucial functional component of bread, but the effect of increasing gluten content on gastrointestinal (GI) function remains uncertain. Our aim was to investigate the effect of increasing gluten content on GI function and symptoms in healthy participants using the unique capabilities of MRI. A total of twelve healthy participants completed this randomised, mechanistic, open-label, three-way crossover study. On days 1 and 2 they consumed either gluten-free bread (GFB), or normal gluten content bread (NGCB) or added gluten content bread (AGCB). The same bread was consumed on day 3, and MRI scans were performed every 60 min from fasting baseline up to 360 min after eating. The appearance of the gastric chime in the images was assessed using a visual heterogeneity score. Gastric volumes, the small bowel water content (SBWC), colonic volumes and colonic gas content and GI symptoms were measured. Fasting transverse colonic volume after the 2-d preload was significantly higher after GFB compared with NGCB and AGCB with a dose-dependent response (289 (SEM 96) v. 212 (SEM 74) v. 179 (SEM 87) ml, respectively; P=0·02). The intragastric chyme heterogeneity score was higher for the bread with increased gluten (AGCB 6 (interquartile range (IQR) 0·5) compared with GFB 3 (IQR 0·5); P=0·003). However, gastric half-emptying time was not different between breads nor were study day GI symptoms, postprandial SBWC, colonic volume and gas content. This MRI study showed novel mechanistic insights in the GI responses to different breads, which are poorly understood notwithstanding the importance of this staple food.

OC-070 Dietary Supplementation With Fodmaps Increases Fasting Colonic Volume And Breath Hydrogen In Healthy Volunteers: A Mechanistic Study Using Mri

Introduction Indigestible fermentable carbohydrates, grouped as FODMAPs, have been proposed to induce gastrointestinal symptoms. Some, such as oligofructose (OF), are prebiotics and modify the microbiota. The metabolic activity of the microbiota affected transit time in a mouse model.1 This study hypothesised that dietary supplementation with OF would shorten whole gut transit time (WGTT) and improve the capacity of the microbiota to metabolise a FODMAP challenge. Methods The study was an open-label case series. 16 healthy volunteers underwent fasting MRI to assess colonic volume [2] and the position of 5 transit markers ingested 24 h earlier from which WGTT could be calculated.3 Breath hydrogen (H2) and methane (CH4) were also measured. Subjects then consumed an inulin challenge drink (ICD): 500 ml water containing 40 g inulin. Inulin is fermented in the colon and known to increase H2 and colonic volume.4 After ICD subjects could sip water and were given a low FODMAP lunch but no other food was allowed. 8 h post-ICD MRI was repeated. Breath measurements were repeated 4 and 8 h post-ICD. Subjects then supplemented their usual diet with OF (gift from BENEO, Germany), 5 g twice daily, for a week. Fasting and post-ICD measurements were then repeated. Dietary questionnaires were completed for the weeks preceding MRIs to assess dietary fructan intake. Abstract OC-070 Figure 1 Results Median [IQR] given unless stated as mean [95% CI]. Fasting colonic volumes (510 ml [400–710]) increased by mean 94 ml [12 – 177, p = 0.03] after OF. Fasting H2 (33 ppm [9–87]) increased by mean 39 ppm [6 – 71, p = 0.02]. WGTT (34 h [10 – 45]) increased by 19 h [-9 – 42] but this increase did not reach significance (p = 0.09, Wilcoxon). Colonic volumes post-ICD were similar across weeks (mean 726 ml [667–785]). The change from baseline was significant in week 1 but not week 2 due to the difference in fasting volumes. There was no difference between weeks 1 and 2 in H2 at 4 or 8 h after ICD. CH4 did not change. Dietary fructan intake was similar in both weeks (mean < 8 g/ day). Conclusion OF increased fasting colonic volumes by 18%. H2 also rose. This may reflect increased bacterial mass with increased capacity for fermentation. The suggestion that OF slows WGTT is surprising and warrants further investigation. MRI can complement research on the microbiota to describe its impact on gut physiology. References 1 Kashyap P et al. Gastroenterology 2013;144(5):967–77 2 Chaddock G et al. Neurogastroenterology and Motility 2013 3 Pritchard S et al. Neurogastroenterol Motil 2013 4 Murray K et al. Am J Gastroenterol 2013 Disclosure of Interest None Declared.

Guidelines for the investigation of chronic diarrhoea in adults: British Society of Gastroenterology, 3rd edition

Chronic diarrhoea is a common problem, hence clear guidance on investigations is required. This is an updated guideline from 2003 for the investigations of chronic diarrhoea commissioned by the Clinical Services and Standards Committee of the British Society of Gastroenterology (BSG). This document has undergone significant revision in content through input by 13 members of the Guideline Development Group (GDG) representing various institutions. The GRADE system was used to appraise the quality of evidence and grading of recommendations.

Coinfection and Emergence of Rifamycin Resistance during a Recurrent Clostridium difficile Infection

ABSTRACT Clostridium difficile (Peptoclostridium difficile) is a common health care-associated infection with a disproportionately high incidence in elderly patients. Disease symptoms range from mild diarrhea to life-threatening pseudomembranous colitis. Around 20% of patients may suffer recurrent disease, which often requires rehospitalization of patients. C. difficile was isolated from stool samples from a patient with two recurrent C. difficile infections. PCR ribotyping, whole-genome sequencing, and phenotypic assays were used to characterize these isolates. Genotypic and phenotypic screening of C. difficile isolates revealed multiple PCR ribotypes present and the emergence of rifamycin resistance during the infection cycle. Understanding both the clinical and bacterial factors that contribute to the course of recurrent infection could inform strategies to reduce recurrence. (This study has been registered at ClinicalTrials.gov under registration no. NCT01670149.)

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