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Irritable Bowel Syndrome: HELP
Articles from Queen Mary University of London
Based on 33 articles published since 2010
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These are the 33 published articles about Irritable Bowel Syndrome that originated from Queen Mary University of London during 2010-2020.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Review Role of brain imaging in disorders of brain-gut interaction: a Rome Working Team Report. 2019

Mayer, Emeran A / Labus, Jennifer / Aziz, Qasim / Tracey, Irene / Kilpatrick, Lisa / Elsenbruch, Sigrid / Schweinhardt, Petra / Van Oudenhove, Lukas / Borsook, David. ·G. Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche and Tamar Manoukian Division of Digestive Diseases David Geffen School of Medicine at UCLA, Los Angeles, California, USA. · Neurogastroenterology Group, Queen Mary University of London, London, UK. · Departments of Anaesthetics and Clinical Neurology, Pembroke College, Oxford, UK. · Institute of Medical Psychology & Behavioral Immunobiology, University Hospital Essen, University of Duisburg, Duisburg, Germany. · Division of Biomedical Sciences, McGill University, Canada. · Translational Research in GastroIntestinal Disorders, KU Leuven Department of Clinical and Experimental Medicine, University of Leuven, Leuven, Belgium. · Center for Pain and the Brain, Boston Children's, Massachusetts General and McLean Hospitals, Harvard Medical School, Boston, Massachusetts, USA. ·Gut · Pubmed #31175206.

ABSTRACT: Imaging of the living human brain is a powerful tool to probe the interactions between brain, gut and microbiome in health and in disorders of brain-gut interactions, in particular IBS. While altered signals from the viscera contribute to clinical symptoms, the brain integrates these interoceptive signals with emotional, cognitive and memory related inputs in a non-linear fashion to produce symptoms. Tremendous progress has occurred in the development of new imaging techniques that look at structural, functional and metabolic properties of brain regions and networks. Standardisation in image acquisition and advances in computational approaches has made it possible to study large data sets of imaging studies, identify network properties and integrate them with non-imaging data. These approaches are beginning to generate brain signatures in IBS that share some features with those obtained in other often overlapping chronic pain disorders such as urological pelvic pain syndromes and vulvodynia, suggesting shared mechanisms. Despite this progress, the identification of preclinical vulnerability factors and outcome predictors has been slow. To overcome current obstacles, the creation of consortia and the generation of standardised multisite repositories for brain imaging and metadata from multisite studies are required.

2 Review Understanding Neurogastroenterology From Neuroimaging Perspective: A Comprehensive Review of Functional and Structural Brain Imaging in Functional Gastrointestinal Disorders. 2018

Kano, Michiko / Dupont, Patrick / Aziz, Qasim / Fukudo, Shin. ·Frontier Research Institute for Interdisciplinary Sciences (FRIS), Tohoku University, Sendai, Japan. · Behavioral Medicine, Graduate School of Medicine, Tohoku University, Sendai, Japan. · Psychosomatic Medicine, Tohoku University Hospital, Sendai, Japan. · Laboratory for Cognitive Neurology, KU Leuven, Belgium. · Center for Digestive Diseases, Wingate Institute of Neurogastroenterology, Barts and the London School of Medicine and Dentistry, Queen Mary College, University of London, UK. ·J Neurogastroenterol Motil · Pubmed #30041284.

ABSTRACT: This review provides a comprehensive overview of brain imaging studies of the brain-gut interaction in functional gastrointestinal disorders (FGIDs). Functional neuroimaging studies during gut stimulation have shown enhanced brain responses in regions related to sensory processing of the homeostatic condition of the gut (homeostatic afferent) and responses to salience stimuli (salience network), as well as increased and decreased brain activity in the emotional response areas and reduced activation in areas associated with the top-down modulation of visceral afferent signals. Altered central regulation of the endocrine and autonomic nervous responses, the key mediators of the brain-gut axis, has been demonstrated. Studies using resting-state functional magnetic resonance imaging reported abnormal local and global connectivity in the areas related to pain processing and the default mode network (a physiological baseline of brain activity at rest associated with self-awareness and memory) in FGIDs. Structural imaging with brain morphometry and diffusion imaging demonstrated altered gray- and white-matter structures in areas that also showed changes in functional imaging studies, although this requires replication. Molecular imaging by magnetic resonance spectroscopy and positron emission tomography in FGIDs remains relatively sparse. Progress using analytical methods such as machine learning algorithms may shift neuroimaging studies from brain mapping to predicting clinical outcomes. Because several factors contribute to the pathophysiology of FGIDs and because its population is quite heterogeneous, a new model is needed in future studies to assess the importance of the factors and brain functions that are responsible for an optimal homeostatic state.

3 Review A fresh look at IBS-opportunities for systems medicine approaches. 2017

Albusoda, A / Barki, N / Herregods, T / Kamphuis, J B J / Karunaratne, T B / Lazarou, M / Lee, I / Mazurak, N / Perna, E / Polster, A / Pribic, T / Uhlig, F / Wang, H / Enck, P. ·Queen Mary and Westfield College University of London, London, UK. · Technische Universität München, Munich, Germany. · Academisch Medisch Centrum bij de Universiteit, Amsterdam, The Netherlands. · Institut National de la Recherche Agronomique, Toulouse, France. · Alma Mater Studiorum Università di Bologna, Bologna, Italy. · Eberhard Karls Universität Tübingen, Tübingen, Germany. · Symbio Pharm GmbH, Herborn, Germany. · Katholieke Universiteit Leuven, Leuven, Belgium. · Göteborgs Universitet, Gothenburg, Sweden. · Fundacio Hospital Universitari Vall d'Hebron, Institut de Recerca, Barcelona, Spain. · University of Sheffield, Sheffield, UK. ·Neurogastroenterol Motil · Pubmed #27997070.

ABSTRACT: NeuroGUT is a EU-funded initial training network (ITN) of 14 research projects in neurogastroenterology that have employed an equal number of early-stage researchers. Neurogut trainees have-among other activities-attended an international conference on irritable bowel syndrome (IBS) in Bologna in 2016 and were asked to critically review and evaluate the current knowledge on IBS for their respective research activities, and to state what they were missing. Most appreciated were the topics brain imaging of gut activity, the role of the gut microbiota, the pharmacology of gut functions, the IBS-IBD interrelation, the new Rome IV criteria, the role of gas, and the placebo response in functional disorders. Missed were more detailed coverage of high-resolution manometry, functional brain imaging, advanced "systems medicine" approaches and bioinformatics technology, better sub-classification of IBS patients, and the development of disease biomarkers, extended at the molecular (genetic/epigenetic, proteonomic) level. They summarize that despite excellent specialized research, there is a gap open that should be filled with systems medicine. For this, it would be necessary that medical research learns even more from the data sciences and other basic disciplines, for example, information technology and system biology, and also welcomes a change in paradigm that enhances open sharing of data, information, and resources.

4 Review Phenotyping of subjects for large scale studies on patients with IBS. 2016

Boeckxstaens, G E / Drug, V / Dumitrascu, D / Farmer, A D / Hammer, J / Hausken, T / Niesler, B / Pohl, D / Pojskic, L / Polster, A / Simren, M / Goebel-Stengel, M / Van Oudenhove, L / Vassallo, M / Wensaas, K-A / Aziz, Q / Houghton, L A / Anonymous15950871. ·Translational Research Center for Gastrointestinal Disorders, KULeuven & Department of Gastroenterology and Hepatology, University Hospital Leuven, Leuven, Belgium. · Gastroenterology Department, University Hospital "St Spiridon", Gr. T.Popa University of Medicine and Pharmacy, Iasi, Romania. · 2nd Medical Dept., Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania. · Wingate Institute of Neurogastroenterology, Barts and The London School of Medicine and Dentistry, London, UK. · Department of Gastroenterology, University Hospitals of North Midlands, Stoke on Trent, UK. · Medizinische Universität Wien, Universitätsklinik für Innere Medizin 3, Vienna, Austria. · Department of Medicine, Unit of Gastroenterology, Haukeland University Hospital, Bergen, Norway. · Department of Human Molecular Genetics, University of Heidelberg, Heidelberg, Germany. · Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland. · Institute for Genetic Engineering and Biotechnology, University of Sarajevo, Sarajevo, Bosnia and Herzegovina. · Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. · Center for Functional Gastrointestinal and Motility Disorders, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. · Department of Internal Medicine, Martin-Luther-Krankenhaus, Berlin, Germany. · Department of Medicine, Mater Dei Hospital, Tal-Qroqq, Malta. · Uni Research Health, Research Unit for General Practice, Bergen, Norway. · Leeds Institute of Biomedical and Clinical Sciences, University of Leeds and Leeds Gastroenterology Institute, Leeds Teaching Hospitals Trust, Leeds, UK. · Centre for Gastrointestinal Sciences, University of Manchester, Manchester, UK. · Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA. ·Neurogastroenterol Motil · Pubmed #27319981.

ABSTRACT: BACKGROUND: Irritable bowel syndrome (IBS) is a complex condition with multiple factors contributing to its aetiology and pathophysiology. Aetiologically these include genetics, life-time events and environment, and physiologically, changes in motility, central processing, visceral sensitivity, immunity, epithelial permeability and gastrointestinal microflora. Such complexity means there is currently no specific reliable biomarker for IBS, and thus IBS continues to be diagnosed and classified according to symptom based criteria, the Rome Criteria. Carefully phenotyping and characterisation of a 'large' pool of IBS patients across Europe and even the world however, might help identify sub-populations with accuracy and consistency. This will not only aid future research but improve tailoring of treatment and health care of IBS patients. PURPOSE: The aim of this position paper is to discuss the requirements necessary to standardize the process of selecting and phenotyping IBS patients and how to organise the collection and storage of patient information/samples in such a large multi-centre pan European/global study. We include information on general demographics, gastrointestinal symptom assessment, psychological factors, quality of life, physiological evaluation, genetic/epigenetic and microbiota analysis, biopsy/blood sampling, together with discussion on the organisational, ethical and language issues associated with implementing such a study. The proposed approach and documents selected to be used in such a study was the result of a thoughtful and thorough four-year dialogue amongst experts associated with the European COST action BM1106 GENIEUR (www.GENIEUR.eu).

5 Review Irritable bowel syndrome. 2016

Enck, Paul / Aziz, Qasim / Barbara, Giovanni / Farmer, Adam D / Fukudo, Shin / Mayer, Emeran A / Niesler, Beate / Quigley, Eamonn M M / Rajilić-Stojanović, Mirjana / Schemann, Michael / Schwille-Kiuntke, Juliane / Simren, Magnus / Zipfel, Stephan / Spiller, Robin C. ·Department of Internal Medicine VI (Psychosomatic Medicine and Psychotherapy), University Hospital Tübingen, Tübingen, Germany. · Wingate Institute of Neurogastroenterology, Barts and London School of Medicine and Dentistry, Queen Mary University of London, London, UK. · Department of Medical and Surgical Sciences, St. Orsola-Malpighi Hospital, Bologna, Italy. · Department of Behavioural Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan. · Oppenheimer Center for Neurobiology of Stress, Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, California, USA. · Department of Human Molecular Genetics, University of Heidelberg, Heidelberg, Germany. · Lynda K and David M Underwood Center for Digestive Disorders, Division of Gastroenterology and Hepatology, Houston Methodist Hospital, Weill Cornell Medical College, Houston, Texas, USA. · Department of Biochemical Engineering and Biotechnology, Faculty of Technology and Metallurgy, University of Belgrade, Belgrade, Serbia. · Department of Human Biology, Technical University Munich, Freising-Weihenstephan, Germany. · Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. · NIHR Nottingham Digestive Diseases Biomedical Research Unit, University of Nottingham, Nottingham, UK. ·Nat Rev Dis Primers · Pubmed #27159638.

ABSTRACT: Irritable bowel syndrome (IBS) is a functional gastrointestinal disease with a high population prevalence. The disorder can be debilitating in some patients, whereas others may have mild or moderate symptoms. The most important single risk factors are female sex, younger age and preceding gastrointestinal infections. Clinical symptoms of IBS include abdominal pain or discomfort, stool irregularities and bloating, as well as other somatic, visceral and psychiatric comorbidities. Currently, the diagnosis of IBS is based on symptoms and the exclusion of other organic diseases, and therapy includes drug treatment of the predominant symptoms, nutrition and psychotherapy. Although the underlying pathogenesis is far from understood, aetiological factors include increased epithelial hyperpermeability, dysbiosis, inflammation, visceral hypersensitivity, epigenetics and genetics, and altered brain-gut interactions. IBS considerably affects quality of life and imposes a profound burden on patients, physicians and the health-care system. The past decade has seen remarkable progress in our understanding of functional bowel disorders such as IBS that will be summarized in this Primer.

6 Review The voltage-gated sodium channel NaV 1.9 in visceral pain. 2016

Hockley, J R F / Winchester, W J / Bulmer, D C. ·Wingate Institute of Neurogastroenterology, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK. · National Centre for Bowel Research and Surgical Innovation, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK. · Neusentis (Pfizer Ltd.), Cambridge, UK. ·Neurogastroenterol Motil · Pubmed #26462871.

ABSTRACT: BACKGROUND: Visceral pain is a common symptom for patients with gastrointestinal (GI) disease. It is unpleasant, debilitating, and represents a large unmet medical need for effective clinical treatments. Recent studies have identified NaV 1.9 as an important regulator of afferent sensitivity in visceral pain pathways to mechanical and inflammatory stimuli, suggesting that NaV 1.9 could represent an important therapeutic target for the treatment of visceral pain. This potential has been highlighted by the identification of patients who have an insensitivity to pain or painful neuropathies associated with mutations in SCN11A, the gene encoding voltage-gated sodium channel subtype 1.9 (NaV 1.9). PURPOSE: Here, we address the role of NaV 1.9 in visceral pain and what known human NaV 1.9 mutants can tell us about NaV 1.9 function in gut physiology and pathophysiology.

7 Review Systematic review: instruments to assess abdominal pain in irritable bowel syndrome. 2015

Mujagic, Z / Keszthelyi, D / Aziz, Q / Reinisch, W / Quetglas, E G / De Leonardis, F / Segerdahl, M / Masclee, A A M. ·Division Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, The Netherlands. · Centre for Digestive Diseases, Blizard Institute of Cell & Molecular Science, Wingate Institute of Neurogastroenterology, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, UK. · Department Internal Medicine III, Medical University of Vienna, Vienna, Austria. · McMaster University, Hamilton, ON, Canada. · Medical Intelligence, Early Clinical Development, Grünenthal GmBH, Aachen, Germany. · Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden. ·Aliment Pharmacol Ther · Pubmed #26290286.

ABSTRACT: BACKGROUND: Consensus on standard methods to assess chronic abdominal pain in patients with irritable bowel syndrome (IBS) is currently lacking. AIM: To systematically review the literature with respect to instruments of measurement of chronic abdominal pain in IBS patients. METHODS: Systematic literature search was performed in PubMed/Medline databases for studies using pain measurement instruments in patients with IBS. RESULTS: One hundred and ten publications were reviewed. A multitude of different instruments is currently used to assess chronic abdominal pain in IBS patients. The single-item methods, e.g. the validated 10-point numeric rating scale (NRS), and questionnaires assessing gastrointestinal symptoms severity, focus mostly on the assessment of only the intensity of abdominal pain. Of these questionnaires, the validated IBS-Symptom Severity Scale includes the broadest measurement of pain-related aspects. General pain questionnaires and electronic momentary symptom assessment tools have been used to study abdominal pain in IBS patients, but have not yet been validated for this purpose. The evidence for the use of provocation tests, e.g. the rectal barostat with balloon distention, for measurement of abdominal pain in IBS is weak, due to the poor correlation between visceral pain thresholds assessed by provocation tests and abdominal pain as assessed by retrospective questionnaires. CONCLUSIONS: The multitude of different instruments to measure chronic abdominal pain in IBS makes it difficult to compare endpoints of published studies. There is need for validated instruments to assess chronic abdominal pain in IBS patients, that overcome the limitations of the currently available methods.

8 Review Systematic review with meta-analysis: the prevalence of bile acid malabsorption in the irritable bowel syndrome with diarrhoea. 2015

Slattery, S A / Niaz, O / Aziz, Q / Ford, A C / Farmer, A D. ·Neurogastroenterology Group, Blizard Institute of Cell & Molecular Science, Wingate Institute of Neurogastroenterology, Barts & the London School of Medicine & Dentistry, Queen Mary University of London, London, UK. · Blackpool Victoria Hospital, Blackpool, UK. · Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK. · Leeds Institute of Biomedical and Clinical Sciences, Leeds University, Leeds, UK. · Department of Gastroenterology, University Hospitals of the North Midlands, Stoke on Trent, UK. ·Aliment Pharmacol Ther · Pubmed #25913530.

ABSTRACT: BACKGROUND: Irritable bowel syndrome is a widespread disorder with a marked socioeconomic burden. Previous studies support the proposal that a subset of patients with features compatible with diarrhoea-predominant IBS (IBS-D) have bile acid malabsorption (BAM). AIM: To perform a systematic review and meta-analysis to assess the prevalence of BAM in patients meeting the accepted criteria for IBS-D. METHODS: MEDLINE and EMBASE were searched up to March 2015. Studies recruiting adults with IBS-D, defined by the Manning, Kruis, Rome I, II or III criteria and which used 23-seleno-25-homotaurocholic acid (SeHCAT) testing for the assessment of BAM were included. BAM was defined as 7 day SeHCAT retention of <10%. We calculated the rate of BAM and 95% confidence intervals (CI) using a random effects model. The methodological quality of included studies was evaluated using the Quality Assessment for Diagnostic Accuracy Studies (QUADAS-2). RESULTS: The search strategy identified six relevant studies comprising 908 individuals. The rate of BAM ranged from 16.9% to 35.3%. The pooled rate was 28.1% (95% CI: 22.6-34%). There was significant heterogeneity in effect sizes (Q-test χ(2)  = 17.9, P < 0.004; I(2)  = 72.1%). The type of diagnostic criteria used or study country did not significantly modify the effect. CONCLUSIONS: These data provide evidence that in excess of one quarter of patients meeting accepted criteria for IBS-D have bile acid malabsorption. This distinction has implications for the interpretation of previous studies, as well as contemporaneous clinical practice and future guideline development.

9 Review The brain-gut axis in health and disease. 2014

Al Omran, Yasser / Aziz, Qasim. ·Centre for Digestive Diseases, Wingate Institute of Neurogastroenterology, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary, University of London, London, UK. ·Adv Exp Med Biol · Pubmed #24997032.

ABSTRACT: The interaction between the brain and the gut has been recognized for many centuries. This bidirectional interaction occurs via neural, immunological and hormonal routes, and is important not only in normal gastrointestinal function but also plays a significant role in shaping higher cognitive function such as our feelings and our subconscious decision-making. Therefore, it remains unsurprising that perturbations in normal signalling have been associated with a multitude of disorders, including inflammatory and functional gastrointestinal disorders, and eating disorders.

10 Review Mechanisms and efficacy of dietary FODMAP restriction in IBS. 2014

Staudacher, Heidi M / Irving, Peter M / Lomer, Miranda C E / Whelan, Kevin. ·King's College London, School of Medicine, Diabetes and Nutritional Sciences Division, Franklin Wilkins Building, 150 Stamford Street, London SE1 9NH, UK. · Guys and St Thomas NHS Foundation Trust, Department of Gastroenterology, College House, St Thomas' Hospital, Westminster Bridge Road, London SE1 7EH, UK. ·Nat Rev Gastroenterol Hepatol · Pubmed #24445613.

ABSTRACT: IBS is a debilitating condition that markedly affects quality of life. The chronic nature, high prevalence and associated comorbidities contribute to the considerable economic burden of IBS. The pathophysiology of IBS is not completely understood and evidence to guide management is variable. Interest in dietary intervention continues to grow rapidly. Ileostomy and MRI studies have demonstrated that some fermentable carbohydrates increase ileal luminal water content and breath hydrogen testing studies have demonstrated that some carbohydrates also increase colonic hydrogen production. The effects of fermentable carbohydrates on gastrointestinal symptoms have also been well described in blinded, controlled trials. Dietary restriction of fermentable carbohydrates (popularly termed the 'low FODMAP diet') has received considerable attention. An emerging body of research now demonstrates the efficacy of fermentable carbohydrate restriction in IBS; however, limitations still exist with this approach owing to a limited number of randomized trials, in part due to the fundamental difficulty of placebo control in dietary trials. Evidence also indicates that the diet can influence the gut microbiota and nutrient intake. Fermentable carbohydrate restriction in people with IBS is promising, but the effects on gastrointestinal health require further investigation.

11 Review Emerging receptor target in the pharmacotherapy of irritable bowel syndrome with constipation. 2013

Blackshaw, L Ashley / Brierley, Stuart M. ·Nerve-Gut Research Laboratory, Discipline of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, Australia. a.blackshaw@qmul.ac.uk ·Expert Rev Gastroenterol Hepatol · Pubmed #23859756.

ABSTRACT: Preclinical experiments in rodent models have recently provided new information on the mechanisms underlying pain sensation in chronic visceral hypersensitivity, as well as insights into the mechanism of action of new drugs targeting abdominal pain in irritable bowel syndrome (IBS). This article describes the evidence base supporting the role of guanylate cyclase C (GC-C) activation in the modulation of gastrointestinal transit and, in particular, in visceral hypersensitivity. We propose that GC-C activation represents an important emerging target for pharmacotherapy in IBS with constipation (IBS-C), particularly given the recent regulatory approval of the GC-C agonist linaclotide as a treatment for IBS-C. More specifically, we address the following questions: "How is pain transmitted from the colon?"; "How is abdominal pain increased in IBS-C?"; "How can we reduce IBS-related abdominal pain - what drugs have been developed?"; "Does linaclotide reduce abdominal pain in animals and humans?"; and "How does linaclotide reduce abdominal pain?".

12 Review Probiotics in the management of irritable bowel syndrome and inflammatory bowel disease. 2013

Whelan, Kevin / Quigley, Eamonn M M. ·King's College London, School of Medicine, Diabetes and Nutritional Sciences Division, London, UK. kevin.whelan@kcl.ac.uk ·Curr Opin Gastroenterol · Pubmed #23286925.

ABSTRACT: PURPOSE OF REVIEW: There is direct evidence that the pathogenesis of inflammatory bowel disease (IBD) involves the gastrointestinal microbiota and some evidence that the microbiota might also play a similar role in irritable bowel syndrome (IBS). The aim of this article is to review the emerging evidence for the mechanisms and effectiveness of probiotics in the management of these disorders. RECENT FINDINGS: The composition of the gastrointestinal microbiota is strongly influenced by factors including age, diet and disease. Probiotics may be effective through their impact on the host gastrointestinal microbiota and promotion of mucosal immunoregulation. Probiotics are considered to be well tolerated, although the quality of studies and health claims has been variable. There are many short-term studies demonstrating the effectiveness of probiotics in IBS, although recommendations should be made for specific strains and for specific symptoms. Within IBD, a number of trials have shown the benefits of a range of probiotics in pouchitis and in ulcerative colitis, although current evidence in Crohn's disease is less promising. SUMMARY: Clearly, some probiotics have considerable potential in the management of IBS and IBD; however, the benefits are strain specific. High-quality trials of probiotics in gastrointestinal disorders as well as laboratory investigations of their mechanism of action are required in order to understand who responds and why.

13 Review Achieving translation in models of visceral pain. 2011

Bulmer, David Colin / Grundy, David. ·Wingate Institute of Neurogastroenterology, Blizard Institute, Bart's and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AJ, United Kingdom. d.bulmer@qmul.ac.uk ·Curr Opin Pharmacol · Pubmed #22000605.

ABSTRACT: The failure of drugs to modify pain end points in clinical trials for irritable bowel syndrome (IBS) highlights the knowledge gap that exists in the translation of efficacy in animal models of visceral pain into the clinic. Recent progress has been made towards improving the translation of visceral pain, particularly with regard to the activation of the sensory nerves which relay pain from the gut to the brain. This review will focus on studies which have identified the presence of an altered gastrointestinal and immune environment in IBS patients. The development of human gastrointestinal visceral afferent recordings has allowed direct comparison between sensory nerve studies in animals and human, as well as important advances in our understanding of the ion channels that underpin the changes in sensory nerve excitability.

14 Review Probiotics and prebiotics in the management of irritable bowel syndrome: a review of recent clinical trials and systematic reviews. 2011

Whelan, Kevin. ·King's College London, School of Medicine, Diabetes and Nutritional Sciences Division, London, UK. kevin.whelan@kcl.ac.uk ·Curr Opin Clin Nutr Metab Care · Pubmed #21892075.

ABSTRACT: PURPOSE OF REVIEW: Irritable bowel syndrome (IBS) is a common disorder of the gastrointestinal tract, about which there has been considerable recent research. The aim of this article is to briefly review the aspects of IBS pathogenesis that involve the gastrointestinal microbiota, and then to critically appraise the recent and emerging evidence for the use of probiotics and prebiotics in its management. RECENT FINDINGS: The increased risk of developing IBS following gastroenteritis and the co-existence of dysbiosis, elevated luminal gas production and immune activation, indicate that the gastrointestinal microbiota may be a therapeutic target in IBS. Most systematic reviews indicate that probiotics have a beneficial impact on global IBS symptoms, abdominal pain and flatulence. However, recent trials indicate that different probiotics can improve, have no effect, or even worsen symptoms, confirming that benefits are likely to be strain and symptom-specific. There are no recent clinical trials of prebiotics in IBS, although previous studies indicate potential benefit at lower doses. SUMMARY: Clearly, some probiotics have considerable potential in the management of IBS; however, the benefits are likely to be strain-specific. Preliminary studies suggest low doses of prebiotics may improve symptoms of IBS, although further robust clinical trials are required.

15 Clinical Trial Linaclotide increases cecal pH, accelerates colonic transit, and increases colonic motility in irritable bowel syndrome with constipation. 2019

Farmer, Adam D / Ruffle, James K / Hobson, Anthony R. ·University of Keele, Keele, UK. · Neurogastroenterology Group, Centre for Neuroscience and Trauma, Blizard Institute, Wingate Institute of Neurogastroenterology, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, UK. · Department of Gastroenterology, University Hospitals of North Midlands, Stoke on Trent, UK. · The Functional Gut Clinic, London, UK. ·Neurogastroenterol Motil · Pubmed #30353623.

ABSTRACT: BACKGROUND: Linaclotide is efficacious in the management of irritable bowel syndrome with constipation (IBS-C), yet relatively little is known regarding its effect on human gastrointestinal physiology. The primary aim of the study was to examine the effect of linaclotide on change in pH across the ileocecal junction (ICJ), a proposed measure of cecal fermentation, and its relationship to symptoms and quality of life (QoL) in IBS-C. METHODS: A total of 13 participants with Rome III IBS-C underwent a standardized wireless motility capsule (WMC). Stool consistency was measured using the Bristol stool form scale (BSFS) and frequency with spontaneous bowel movements (SBM). Gastrointestinal symptoms and QoL were assessed using validated questionnaires. The WMC and questionnaires were repeated after 28 days of linaclotide 290 g po od. KEY RESULTS: Linaclotide reduced the change in pH across the ICJ (-2.4 ± 0.2 vs -2.1 ± 0.4, P = 0.01) as a function of a relative alkalinization of the cecum (5.2 ± 0.2 vs 5.5 ± 0.3, P = 0.02). Linaclotide accelerated colonic transit time (2650 minutes (2171-4038) vs. 1757 (112-3011), P = 0.02), increased colonic log motility index (15 ± 1.8 vs. 16.5 ± 1.8, P = 0.004) but had no effect of gastric emptying or small bowel transit. Change in pH across the ICJ correlated with improvement in symptom intensity, unpleasantness, and visceral sensitivity index (r = 0.62, P = 0.03, r = 0.63, P = 0.02, r = 0.62, P = 0.02) and with increases in BSFS type and SBM (r = 0.9, P < 0.0001, r = 0.6, P = 0.02). CONCLUSIONS & INFERENCES: Linaclotide's effects are confined to the colon where it increases cecal pH, potentially representing a reduction in cecal fermentation and accelerates colonic motility.

16 Article Randomised, double-blind, placebo controlled multi-centre study to assess the efficacy, tolerability and safety of Enterosgel® in the treatment of irritable bowel syndrome with diarrhoea (IBS-D) in adults. 2020

Kemppinen, Anu / Howell, Carol / Allgar, Victoria / Dodd, Matthew / Gregson, John / Knowles, Charles / McLaughlin, John / Pandya, Preeti / Whorwell, Peter / Markaryan, Elena / Yiannakou, Yan. ·Clever Cookie Ltd, Hove, UK. anu@clevercookie.net. · Enteromed Ltd, London, UK. · Department of Health Sciences, University of York, York, UK. · Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK. · Queen Mary University of London, London, UK. · Division of Diabetes, Endocrinology and Gastroenterology, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK. · Salford Royal NHS Foundation Trust, Salford, UK. · The Village Practice, Thornton-Cleveleys, UK. · Centre for Gastrointestinal Sciences, University of Manchester, Manchester, UK. · County Durham and Darlington NHS Foundation Trust, University Hospital of North Durham, Durham, UK. ·Trials · Pubmed #32000822.

ABSTRACT: BACKGROUND: Irritable bowel syndrome (IBS) with diarrhoea (IBS-D) is a common and chronic condition that can significantly impair quality of life. The emergence of new drugs for IBS-D has been slow and there is a need for new treatments, including drug-free treatments, which are easy to use and suitable for different patient groups. Currently available drug-free treatments include Enterosgel®, an intestinal adsorbent approved for use in IBS-D and acute diarrhoea and available over-the-counter in the UK and 30 countries worldwide. The aim of this randomised, double-blind, placebo-controlled, multi-centre study is to test the efficacy and safety of Enterosgel® compared to placebo in symptomatic treatment in IBS-D. METHODS/DESIGN: We will recruit 430 participants with IBS-D from approximately 30 primary and secondary care sites in England. Participants meeting the required abdominal pain and stool consistency criteria over a 2-week screening period will be randomly allocated to receive blinded treatment (Enterosgel® or placebo) for 8 weeks. This will be followed by an 8-week open-label treatment phase with Enterosgel®. Participants will be allowed to adjust their daily dosage during both phases based on their symptoms. Participants will then return to standard care and those who responded to treatment will receive a follow-up call 8 weeks later. Co-medication with loperamide will be permitted and use recorded. The primary outcome measure is the percentage of participants defined as responders for abdominal pain and stool consistency during at least 4 weeks in the 8-week blinded phase. Secondary outcome measures include stool frequency, stool consistency, abdominal pain, bloating, urgency, adequate relief, questionnaire scores and rescue medication use. Exploratory outcomes will be assessed in subsets of participants including qualitative and quantitative data on faecal microorganisms and biomarkers and gut-related measurements from magnetic resonance imaging data. DISCUSSION: This is the first large scale randomised controlled trial investigating Enterosgel® in IBS-D. A study design with blinded phase followed by an open-label phase was chosen to encourage participation and study completion. Demonstrating that Enterosgel® is effective and safe in IBS-D could encourage adoption by patients and healthcare professionals and foster future clinical trials assessing its use in related conditions. TRIAL REGISTRATION: ISRCTN17149988. Prospectively registered on 14 November 2017.

17 Article Treatment of irritable bowel syndrome with diarrhoea using titrated ondansetron (TRITON): study protocol for a randomised controlled trial. 2019

Gunn, David / Fried, Ron / Lalani, Rabia / Farrin, Amanda / Holloway, Ivana / Morris, Tom / Olivier, Catherine / Kearns, Rachael / Corsetti, Maura / Scott, Mark / Farmer, Adam / Emmanuel, Anton / Whorwell, Peter / Yiannakou, Yan / Sanders, David / Mclaughlin, John / Kapur, Kapil / Eugenicos, Maria / Akbar, Ayesha / Trudgill, Nigel / Houghton, Lesley / Dinning, Phil G / Ford, Alexander C / Aziz, Qasim / Spiller, Robin. ·NIHR Nottingham Digestive Diseases Biomedical Research Centre, University of Nottingham, Nottingham, UK. · Nottingham Digestive Diseases Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK. · Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK. · Wingate Institute of Neurogastroenterology, Queen Mary University of London, London, UK. · Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK. · Royal Stoke Hospital, University Hospitals of North Midlands NHS Trust, Stoke, UK. · University College London Hospital, University College London Hospitals NHS Foundation Trust, London, UK. · Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK. · County Durham and Darlington Foundation Trust, University Hospital of North Durham, Durham, UK. · Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK. · Salford Royal NHS Foundation Trust, Salford Royal University Hospital, Manchester, UK. · Barnsley Hospital, Barnsley Hospital NHS Foundation Trust, Barnsley, UK. · Western General Hospital Edinburgh, NHS Lothian, Edinburgh, UK. · London North West Healthcare NHS Trust, St Mark's Hospital, London, UK. · Sandwell General Hospital, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, UK. · St James's Hospital, Leeds Teaching Hospitals NHS Trust, Leeds, UK. · Discipline of Surgery and Gastroenterology, Flinders Medical Centre, Flinders University, Adelaide, South Australia, Australia. · NIHR Nottingham Digestive Diseases Biomedical Research Centre, University of Nottingham, Nottingham, UK. robin.spiller@nottingham.ac.uk. · Nottingham Digestive Diseases Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK. robin.spiller@nottingham.ac.uk. ·Trials · Pubmed #31429811.

ABSTRACT: BACKGROUND: Irritable bowel syndrome with diarrhoea (IBS-D) affects up to 4% of the general population. Symptoms include frequent, loose, or watery stools with associated urgency, resulting in marked reduction of quality of life and loss of work productivity. Ondansetron, a 5HT METHODS: This trial is a phase III, parallel group, randomised, double-blind, multi-centre, placebo-controlled trial, with embedded mechanistic studies. Participants (n = 400) meeting Rome IV criteria for IBS-D will be recruited from outpatient and primary care clinics and by social media to receive either ondansetron (dose titrated up to 24 mg daily) or placebo for 12 weeks. Throughout the trial, participants will record their worst abdominal pain, worst urgency, stool frequency, and stool consistency on a daily basis. The primary endpoint is the proportion of "responders" in each group, using Food and Drug Administration (FDA) recommendations. Secondary endpoints include pain intensity, stool consistency, frequency, and urgency. Mood and quality of life will also be assessed. Mechanistic assessments will include whole gut transit, faecal tryptase and faecal bile acid concentrations at baseline and between weeks 8 and 11. A subgroup of participants will also undergo assessment of sensitivity (n = 80) using the barostat, and/or high-resolution colonic manometry (n = 40) to assess motor patterns in the left colon and the impact of ondansetron. DISCUSSION: The TRITON trial aims to assess the effect of ondansetron across multiple centres. By defining ondansetron's mechanisms of action we hope to better identify patients with IBS-D who are likely to respond. TRIAL REGISTRATION: ISRCTN, ISRCTN17508514 , Registered on 2 October 2017.

18 Article 5-oxoETE triggers nociception in constipation-predominant irritable bowel syndrome through MAS-related G protein-coupled receptor D. 2018

Bautzova, Tereza / Hockley, James R F / Perez-Berezo, Teresa / Pujo, Julien / Tranter, Michael M / Desormeaux, Cleo / Barbaro, Maria Raffaella / Basso, Lilian / Le Faouder, Pauline / Rolland, Corinne / Malapert, Pascale / Moqrich, Aziz / Eutamene, Helene / Denadai-Souza, Alexandre / Vergnolle, Nathalie / Smith, Ewan St John / Hughes, David I / Barbara, Giovanni / Dietrich, Gilles / Bulmer, David C / Cenac, Nicolas. ·INSERM, UMR1220, IRSD, Université de Toulouse, INRA, ENVT, UPS, Toulouse, France. · Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB1 2PD, UK. · National Centre for Bowel Research and Surgical Innovation, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AJ, UK. · Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy. · INSERM UMR1048, Lipidomic Core Facility, Metatoul Platform, Université de Toulouse, Toulouse, France. · Aix-Marseille-Université, CNRS, Institut de Biologie du Développement de Marseille, UMR 7288, Marseille, France. · Neuro-Gastroenterology and Nutrition Team, UMR 1331, INRA Toxalim, INP-EI-Purpan, Université de Toulouse, Toulouse, France. · Departments of Physiology & Pharmacology, and Medicine, University of Calgary Cumming School of Medicine, 3330 Hospital Drive Northwest, Calgary, Alberta T2N 4N1, Canada. · Institute of Neuroscience and Psychology, University of Glasgow, Glasgow, UK. · INSERM, UMR1220, IRSD, Université de Toulouse, INRA, ENVT, UPS, Toulouse, France. nicolas.cenac@inserm.fr. ·Sci Signal · Pubmed #30563864.

ABSTRACT: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that is characterized by chronic abdominal pain concurrent with altered bowel habit. Polyunsaturated fatty acid (PUFA) metabolites are increased in abundance in IBS and are implicated in the alteration of sensation to mechanical stimuli, which is defined as visceral hypersensitivity. We sought to quantify PUFA metabolites in patients with IBS and evaluate their role in pain. Quantification of PUFA metabolites by mass spectrometry in colonic biopsies showed an increased abundance of 5-oxoeicosatetraenoic acid (5-oxoETE) only in biopsies taken from patients with IBS with predominant constipation (IBS-C). Local administration of 5-oxoETE to mice induced somatic and visceral hypersensitivity to mechanical stimuli without causing tissue inflammation. We found that 5-oxoETE directly acted on both human and mouse sensory neurons as shown by lumbar splanchnic nerve recordings and Ca

19 Article Systematic review with meta-analysis: conditioned pain modulation in patients with the irritable bowel syndrome. 2018

Albusoda, Ahmed / Ruffle, James K / Friis, Kathrine A / Gysan, Maximilian R / Drewes, Asbjørn M / Aziz, Qasim / Farmer, Adam D. ·Centre for Neuroscience and Trauma, Blizard Institute, Wingate Institute of Neurogastroenterology, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, UK. · Faculty of Health Sciences, Aarhus University, Aarhus, Denmark. · School of Medicine, Heidelberg University, Heidelberg, Germany. · Mech-Sense, Department of Gastroenterology and Clinical Medicine, Aalborg University Hospital, Aalborg, Denmark. · Department of Gastroenterology, University Hospitals Midlands NHS Trust, Stoke on Trent, Staffordshire, UK. · Institute of Applied Clinical Science, University of Keele, Keele, Staffordshire, UK. ·Aliment Pharmacol Ther · Pubmed #30206948.

ABSTRACT: BACKGROUND: Irritable bowel syndrome (IBS) is common and is characterised by recurrent abdominal pain, which is a major contributor to healthcare seeking. The neurobiological basis of this pain is incompletely understood. Conditioned pain modulation is a neuromodulatory mechanism through which the brain inhibits the nociceptive afferent barrage through the descending pathways. Reduced conditioned pain modulation has been implicated in the pathophysiology of IBS, although to date only in studies with relatively small sample sizes. AIM: To clarify the relationship between conditioned pain modulation and IBS by undertaking a systemic review and meta-analysis METHODS: A systematic review of MEDLINE and Web of Science databases was searched (up to 10 May 2018). We included studies examining conditioned pain modulation in adults with IBS and healthy subjects. Data were pooled for meta-analysis to calculate the odds ratio and effect size of abnormal conditioned pain modulation in IBS, with 95% confidence intervals (CI). RESULTS: The search strategy identified 645 studies, of which 13 were relevant and 12 met the inclusion criteria. Conditioned pain modulation in IBS patients vs healthy subjects was significantly reduced, odds ratio 4.84 (95% CI: 2.19-10.71, P < 0.0001), Hedges' g effect size of 0.85 (95% CI: 0.42-1.28, P < 0.001). There was significant heterogeneity in effect sizes (Q-test χ CONCLUSION: Conditioned pain modulation is significantly diminished in patients with IBS vs healthy controls. These data suggest that abnormal descending pathways may play an important pathophysiological role in IBS, which could represent an investigation and a therapeutic target in IBS.

20 Article Development, content validity, and cross-cultural adaptation of a patient-reported outcome measure for real-time symptom assessment in irritable bowel syndrome. 2018

Vork, L / Keszthelyi, D / Mujagic, Z / Kruimel, J W / Leue, C / Pontén, I / Törnblom, H / Simrén, M / Albu-Soda, A / Aziz, Q / Corsetti, M / Holvoet, L / Tack, J / Rao, S S / van Os, J / Quetglas, E G / Drossman, D A / Masclee, A A M. ·Division of Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, The Netherlands. · Department of Psychiatry and Medical Psychology, Maastricht University Medical Center+, Maastricht, The Netherlands. · Department of Internal Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. · Center for Functional Gastrointestinal and Motility Disorders, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. · Centre for Neuroscience and Trauma, Wingate Institute of Neurogastroenterology, Blizard Institute, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, UK. · Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium. · Nottingham Digestive Diseases Biomedical Research Unit, National Institute for Health Research, Nottingham University Hospitals NHS Trust, University of Nottingham, Nottingham, UK. · Digestive Health Center, Medical College of Georgia, Georgia Regents University, Augusta, GA, USA. · Medical Intelligence, Early Clinical Development, Grünenthal GmBH, Aachen, Germany. ·Neurogastroenterol Motil · Pubmed #29106029.

ABSTRACT: BACKGROUND: End-of-day questionnaires, which are considered the gold standard for assessing abdominal pain and other gastrointestinal (GI) symptoms in irritable bowel syndrome (IBS), are influenced by recall and ecological bias. The experience sampling method (ESM) is characterized by random and repeated assessments in the natural state and environment of a subject, and herewith overcomes these limitations. This report describes the development of a patient-reported outcome measure (PROM) based on the ESM principle, taking into account content validity and cross-cultural adaptation. METHODS: Focus group interviews with IBS patients and expert meetings with international experts in the fields of neurogastroenterology & motility and pain were performed in order to select the items for the PROM. Forward-and-back translation and cognitive interviews were performed to adapt the instrument for the use in different countries and to assure on patients' understanding with the final items. KEY RESULTS: Focus group interviews revealed 42 items, categorized into five domains: physical status, defecation, mood and psychological factors, context and environment, and nutrition and drug use. Experts reduced the number of items to 32 and cognitive interviewing after translation resulted in a few slight adjustments regarding linguistic issues, but not regarding content of the items. CONCLUSIONS AND INFERENCES: An ESM-based PROM, suitable for momentary assessment of IBS symptom patterns was developed, taking into account content validity and cross-cultural adaptation. This PROM will be implemented in a specifically designed smartphone application and further validation in a multicenter setting will follow.

21 Article Volatile Organic Compounds in Feces Associate With Response to Dietary Intervention in Patients With Irritable Bowel Syndrome. 2018

Rossi, Megan / Aggio, Raphael / Staudacher, Heidi M / Lomer, Miranda C / Lindsay, James O / Irving, Peter / Probert, Chris / Whelan, Kevin. ·Department of Nutritional Sciences, King's College London, London, United Kingdom; Guy's and St Thomas' NHS Foundation Trust, Department of Gastroenterology, London, United Kingdom. · Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom. · Bart's Health NHS Trust, Department of Gastroenterology, United Kingdom, and Barts and the London School of Medicine, Blizard Institute, Queen Mary University of London, London, United Kingdom. · Department of Nutritional Sciences, King's College London, London, United Kingdom. Electronic address: Kevin.whelan@kcl.ac.uk. ·Clin Gastroenterol Hepatol · Pubmed #28993261.

ABSTRACT: BACKGROUND & AIMS: Dietary interventions are effective in management of patients with irritable bowel syndrome (IBS), although responses vary. We investigated whether fecal levels of volatile organic compounds (VOCs) associate with response to dietary interventions in patients with IBS. METHODS: Adults who fulfilled the Rome III criteria for IBS were recruited to a 2x2 factorial randomized controlled trial. Patients were randomly assigned to a group counselled to follow a diet low in fructans, galacto-oligosaccharides, lactose, fructose, and polyols (low-FODMAP diet, n = 46) or a group that received placebo dietary advice (sham diet, n = 47) for 4 weeks. Patients from each group were also given either a multi-strain probiotic or placebo supplement. Response was defined as a reduction of 50 points or more on the validated IBS symptom scoring system. Fecal samples were collected from participants at baseline and end of the 4-week study period; VOCs were analyzed by a gas-chromatography sensor device. VOC profiles were determined using a pipeline involving wavelet transformation followed by feature selection based on random forest. A partial least squares classifier was constructed to classify VOC profiles by response and accuracies were determined using 10-fold cross-validation. RESULTS: Data from 93 patients who completed the study (63 female) were used in the final analysis. More patients responded to the low-FODMAP diet (37/46, 80%) than the sham diet (21/47, 45%) (P < .001), but there was no difference in response between patients given the probiotic (31/49, 63%) vs the placebo (27/44, 61%) (P = .850), with no interaction between the diet and supplement interventions. At baseline, VOC profiles contained 15 features that classified response to the low-FODMAP diet with a mean accuracy of 97% (95% CI, 96%-99%) and 10 features that classified response to probiotic with a mean accuracy of 89% (95% CI, 86%-92%). End of treatment models achieved similar predictive powers and accuracies. CONCLUSION: Fecal VOC profiling is a low cost, non-invasive tool that might be used to predict responses of patients with IBS to low-FODMAP diet and probiotics and identify their mechanisms of action. ISRCTN registry no: 02275221.

22 Article Evidence for long-term sensitization of the bowel in patients with post-infectious-IBS. 2017

Balemans, D / Mondelaers, S U / Cibert-Goton, V / Stakenborg, N / Aguilera-Lizarraga, J / Dooley, J / Liston, A / Bulmer, D C / Vanden Berghe, P / Boeckxstaens, G E / Wouters, M M. ·Translational Research Center for Gastrointestinal Disorders, Dept. of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium. · National Centre for Bowel Research and Surgical Innovation, Centre for Neuroscience and Trauma, Blizard Institute, Bart's and the London school of Medicine and Dentistry, Queen Mary University of London, London, UK. · Autoimmune Genetics Laboratory, VIB and Department of Microbiology and Immunology, KU Leuven, Belgium. · Department of Pharmacology, University of Cambridge, Cambridge, UK. · Translational Research Center for Gastrointestinal Disorders, Dept. of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium. guy.boeckxstaens@med.kuleuven.be. ·Sci Rep · Pubmed #29051514.

ABSTRACT: Post-infectious irritable bowel syndrome (PI-IBS) is a common gastrointestinal disorder characterized by persistent abdominal pain despite recovery from acute gastroenteritis. The underlying mechanisms are unclear, although long-term changes in neuronal function, and low grade inflammation of the bowel have been hypothesized. We investigated the presence and mechanism of neuronal sensitization in a unique cohort of individuals who developed PI-IBS following exposure to contaminated drinking water 7 years ago. We provide direct evidence of ongoing sensitization of neuronal signaling in the bowel of patients with PI-IBS. These changes occur in the absence of any detectable tissue inflammation, and instead appear to be driven by pro-nociceptive changes in the gut micro-environment. This is evidenced by the activation of murine colonic afferents, and sensitization responses to capsaicin in dorsal root ganglia (DRGs) following application of supernatants generated from tissue biopsy of patients with PI-IBS. We demonstrate that neuronal signaling within the bowel of PI-IBS patients is sensitized 2 years after the initial infection has resolved. This sensitization appears to be mediated by a persistent pro-nociceptive change in the gut micro-environment, that has the capacity to stimulate visceral afferents and facilitate neuronal TRPV1 signaling.

23 Article A Diet Low in FODMAPs Reduces Symptoms in Patients With Irritable Bowel Syndrome and A Probiotic Restores Bifidobacterium Species: A Randomized Controlled Trial. 2017

Staudacher, Heidi Maria / Lomer, Miranda C E / Farquharson, Freda M / Louis, Petra / Fava, Francesca / Franciosi, Elena / Scholz, Matthias / Tuohy, Kieran M / Lindsay, James O / Irving, Peter M / Whelan, Kevin. ·Faculty of Life Sciences and Medicine, Diabetes and Nutritional Sciences Division, King's College London, London, United Kingdom. · Faculty of Life Sciences and Medicine, Diabetes and Nutritional Sciences Division, King's College London, London, United Kingdom; Department of Gastroenterology, Guys and St Thomas' NHS Foundation Trust, London, United Kingdom; Department of Nutrition and Dietetics, Guys and St Thomas' NHS Foundation Trust, London, United Kingdom. · The Rowett Institute, University of Aberdeen, Gut Health Group, Aberdeen, United Kingdom. · Research and Innovation Centre, Department of Food Quality and Nutrition, Nutrition and Nutrigenomics Group, Fondazione Edmund Mach, Trento, Italy. · Blizard Institute, Queen Mary University of London, Centre for Immunobiology, London, United Kingdom; Barts Health NHS Trust, London, United Kingdom. · Faculty of Life Sciences and Medicine, Diabetes and Nutritional Sciences Division, King's College London, London, United Kingdom; Department of Gastroenterology, Guys and St Thomas' NHS Foundation Trust, London, United Kingdom. · Faculty of Life Sciences and Medicine, Diabetes and Nutritional Sciences Division, King's College London, London, United Kingdom. Electronic address: kevin.whelan@kcl.ac.uk. ·Gastroenterology · Pubmed #28625832.

ABSTRACT: BACKGROUND & AIMS: Dietary restriction of fermentable carbohydrates (a low FODMAP diet) has been reported to reduce symptoms in some patients with irritable bowel syndrome (IBS). We performed a randomized, placebo-controlled study to determine its effects on symptoms and the fecal microbiota in patients with IBS. METHODS: We performed a 2×2 factorial trial of 104 patients with IBS (18-65 years old), based on the Rome III criteria, at 2 hospitals in the United Kingdom. Patients were randomly assigned (blinded) to groups given counselling to follow a sham diet or diet low in FODMAPs for 4 weeks, along with a placebo or multistrain probiotic formulation, resulting in 4 groups (27 receiving sham diet/placebo, 26 receiving sham diet/probiotic, 24 receiving low FODMAP diet /placebo, and 27 receiving low FODMAP diet/probiotic). The sham diet restricted a similar number of staple and non-staple foods as the low FODMAP diet; the diets had similar degrees of difficulty to follow. Dietary counselling was given to patients in all groups and data on foods eaten and compliance were collected. The incidence and severity of 15 gastrointestinal symptoms and overall symptoms were measured daily for 7 days before the study period; along with stool frequency and consistency. At baseline, global and individual symptoms were measured, along with generic and disease-specific health-related quality of life, using standard scoring systems. All data were collected again at 4 weeks, and patients answered questions about adequate symptom relief. Fecal samples were collected at baseline and after 4 weeks and analyzed by quantitative PCR and 16S rRNA sequencing. The co-primary endpoints were adequate relief of symptoms and stool Bifidobacterium species abundance at 4 weeks. RESULTS: There was no significant interaction between the interventions in adequate relief of symptoms (P = .52) or Bifidobacterium species (P = .68). In the intention-to-treat analysis, a higher proportion of patients in the low FODMAP diet had adequate symptom relief (57%) than in the sham diet group (38%), although the difference was not statistically significant (P = .051). In the per-protocol analysis, a significantly higher proportion of patients on the low FODMAP diet had adequate symptom relief (61%) than in the sham diet group (39%) (P = .042). Total mean IBS-Severity Scoring System score was significantly lower for patients on the low FODMAP diet (173 ± 95) than the sham diet (224 ± 89) (P = .001), but not different between those given probiotic (207 ± 98) or placebo (192 ± 93) (P = .721) Abundance of Bifidobacterium species was lower in fecal samples from patients on the low FODMAP diet (8.8 rRNA genes/g) than patients on the sham diet (9.2 rRNA genes/g) (P = .008), but higher in patients given probiotic (9.1 rRNA genes/g) than patients given placebo (8.8 rRNA genes/g) (P = .019). There was no effect of the low FODMAP diet on microbiota diversity in fecal samples. CONCLUSIONS: In a placebo-controlled study of patients with IBS, a low FODMAP diet associates with adequate symptom relief and significantly reduced symptom scores compared with placebo. It is not clear whether changes resulted from collective FODMAP restriction or removal of a single component, such as lactose. Co-administration of the multistrain probiotic increased numbers of Bifidobacterium species, compared with placebo, and might be given to restore these bacteria to patients on a low FODMAP diet. Trial registration no: ISRCTN02275221.

24 Article Acute colitis chronically alters immune infiltration mechanisms and sensory neuro-immune interactions. 2017

Campaniello, Melissa A / Mavrangelos, Chris / Eade, Samuel / Harrington, Andrea M / Blackshaw, L Ashley / Brierley, Stuart M / Smid, Scott D / Hughes, Patrick A. ·Centre for Nutrition and Gastrointestinal Diseases, University of Adelaide and South Australian Health and Medical Research Institute (SAHMRI), Adelaide, Australia. · Centre for Nutrition and Gastrointestinal Diseases, University of Adelaide and South Australian Health and Medical Research Institute (SAHMRI), Adelaide, Australia; Department of Pharmacology, University of Adelaide, Adelaide, Australia. · Centre for Neuroscience and Trauma, Blizard Institute, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, UK. · Department of Pharmacology, University of Adelaide, Adelaide, Australia. · Centre for Nutrition and Gastrointestinal Diseases, University of Adelaide and South Australian Health and Medical Research Institute (SAHMRI), Adelaide, Australia. Electronic address: patrick.hughes@adelaide.edu.au. ·Brain Behav Immun · Pubmed #27864046.

ABSTRACT: OBJECTIVE: Little is understood regarding how disease progression alters immune and sensory nerve function in colitis. We investigated how acute colitis chronically alters immune recruitment and the impact this has on re-activated colitis. To understand the impact of disease progress on sensory systems we investigated the mechanisms underlying altered colonic neuro-immune interactions after acute colitis. DESIGN: Inflammation was compared in mouse models of health, acute tri-nitrobenzene sulphonic acid (TNBS) colitis, Remission and Reactivated colitis. Cytokine concentrations were compared by ELISA in-situ and in explanted colon tissue. Colonic infiltration by CD11b/F4-80 macrophage, CD4 T RESULTS: Colonic damage, MPO activity, macrophage infiltration, IL-1β and IL-6 concentrations were lower in Reactivated compared to Acute colitis. T CONCLUSIONS: Acute colitis persistently alters immune responses and afferent nerve signalling pathways to successive episodes of colitis. These findings highlight the complexity of viscero-sensory neuro-immune interactions in painful remitting and relapsing diseases.

25 Article Histamine Receptor H1-Mediated Sensitization of TRPV1 Mediates Visceral Hypersensitivity and Symptoms in Patients With Irritable Bowel Syndrome. 2016

Wouters, Mira M / Balemans, Dafne / Van Wanrooy, Sander / Dooley, James / Cibert-Goton, Vincent / Alpizar, Yeranddy A / Valdez-Morales, Eduardo E / Nasser, Yasmin / Van Veldhoven, Paul P / Vanbrabant, Winde / Van der Merwe, Schalk / Mols, Raf / Ghesquière, Bart / Cirillo, Carla / Kortekaas, Inge / Carmeliet, Peter / Peetermans, Willy E / Vermeire, Séverine / Rutgeerts, Paul / Augustijns, Patrick / Hellings, Peter W / Belmans, Ann / Vanner, Stephen / Bulmer, David C / Talavera, Karel / Vanden Berghe, Pieter / Liston, Adrian / Boeckxstaens, Guy E. ·Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders, University Hospital Leuven, KU Leuven, Leuven, Belgium. · Autoimmune Genetics Laboratory, Flemish Institute for Biotechnology (VIB) and Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium. · National Centre for Bowel Research and Surgical Innovation, Centre for Neuroscience and Trauma, Blizard Institute, Bart's and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom. · Department of Cellular and Molecular Medicine, Laboratory of Ion Channel Research and Transient Receptor Potential (TRP) channel Research Platform, KU Leuven, Leuven, Belgium. · Gastrointestinal Diseases Research Unit, Kingston General Hospital, Queen's University, Kingston, Canada. · Department of Cellular and Molecular Medicine, Laboratory of Lipid Biochemistry and Protein-Interaction, KU Leuven, Leuven, Belgium. · Department of Clinical and Experimental Medicine, Hepatology, University Hospital Leuven, KU Leuven, Leuven, Belgium. · Department of Pharmaceutical and Pharmacological Sciences, Drug Delivery and Disposition, University Hospital Leuven, KU Leuven, Leuven, Belgium. · Laboratory of Angiogenesis and Neurovascular Link (Vesalius Research Center), KU Leuven, Leuven, Belgium. · Department of Microbiology and Immunology, Laboratory of Clinical Immunology, KU Leuven, Leuven, Belgium. · Department of Internal Medicine, Laboratory for Clinical Infectious and Inflammatory Disorders, University Hospital Leuven, KU Leuven, Leuven, Belgium. · Department of Microbiology and Immunology, Laboratory of Clinical Immunology, KU Leuven, Leuven, Belgium; Department of Otorhinolaryngology, Academic Medical Center Amsterdam, Amsterdam, The Netherlands; Department of Otorhinolaryngology, University of Ghent, Ghent, Belgium. · Department of Biostatistics and Centre of Statistical Bioinformatics, KU Leuven, Leuven, Belgium. · Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders, University Hospital Leuven, KU Leuven, Leuven, Belgium. Electronic address: guy.boeckxstaens@med.kuleuven.be. ·Gastroenterology · Pubmed #26752109.

ABSTRACT: BACKGROUND & AIMS: Histamine sensitizes the nociceptor transient reporter potential channel V1 (TRPV1) and has been shown to contribute to visceral hypersensitivity in animals. We investigated the role of TRPV1 in irritable bowel syndrome (IBS) and evaluated if an antagonist of histamine receptor H1 (HRH1) could reduce symptoms of patients in a randomized placebo-controlled trial. METHODS: By using live calcium imaging, we compared activation of submucosal neurons by the TRPV1 agonist capsaicin in rectal biopsy specimens collected from 9 patients with IBS (ROME 3 criteria) and 15 healthy subjects. The sensitization of TRPV1 by histamine, its metabolite imidazole acetaldehyde, and supernatants from biopsy specimens was assessed by calcium imaging of mouse dorsal root ganglion neurons. We then performed a double-blind trial of patients with IBS (mean age, 31 y; range, 18-65 y; 34 female). After a 2-week run-in period, subjects were assigned randomly to groups given either the HRH1 antagonist ebastine (20 mg/day; n = 28) or placebo (n = 27) for 12 weeks. Rectal biopsy specimens were collected, barostat studies were performed, and symptoms were assessed (using the validated gastrointestinal symptom rating scale) before and after the 12-week period. Patients were followed up for an additional 2 weeks. Abdominal pain, symptom relief, and health-related quality of life were assessed on a weekly basis. The primary end point of the study was the effect of ebastine on the symptom score evoked by rectal distension. RESULTS: TRPV1 responses of submucosal neurons from patients with IBS were potentiated compared with those of healthy volunteers. Moreover, TRPV1 responses of submucosal neurons from healthy volunteers could be potentiated by their pre-incubation with histamine; this effect was blocked by the HRH1 antagonist pyrilamine. Supernatants from rectal biopsy specimens from patients with IBS, but not from the healthy volunteers, sensitized TRPV1 in mouse nociceptive dorsal root ganglion neurons via HRH1; this effect could be reproduced by histamine and imidazole acetaldehyde. Compared with subjects given placebo, those given ebastine had reduced visceral hypersensitivity, increased symptom relief (ebastine 46% vs placebo 13%; P = .024), and reduced abdominal pain scores (ebastine 39 ± 23 vs placebo 62 ± 22; P = .0004). CONCLUSIONS: In studies of rectal biopsy specimens from patients, we found that HRH1-mediated sensitization of TRPV1 is involved in IBS. Ebastine, an antagonist of HRH1, reduced visceral hypersensitivity, symptoms, and abdominal pain in patients with IBS. Inhibitors of this pathway might be developed as a new treatment approach for IBS. ClinicalTrials.gov no: NCT01144832.

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