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Irritable Bowel Syndrome: HELP
Articles from Manchester, UK
Based on 48 articles published since 2008
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These are the 48 published articles about Irritable Bowel Syndrome that originated from Manchester, UK during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Review New therapeutic options for IBS: the role of the first in class mixed µ- opioid receptor agonist and δ-opioid receptor antagonist (mudelta) eluxadoline. 2017

Corsetti, Maura / Whorwell, Peter. ·a Nottingham Digestive Diseases Biomedical Research Unit , National Institute for Health Research, Nottingham University Hospitals NHS Trust, University of Nottingham , Nottingham , UK. · b Centre for Gastrointestinal Sciences , University of Manchester , Manchester , UK. ·Expert Rev Gastroenterol Hepatol · Pubmed #28276811.

ABSTRACT: INTRODUCTION: Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder which represents a major cost to healthcare services. IBS-D patients represent about one-third of the IBS population and are currently treated with antispasmodics, loperamide, bile acid sequestrants and antidepressants. Alosetron and rifaximin are also available in USA, ramosetron in Japan, Korea and Thailand and ondansetron as an off-label treatment. Areas covered: This article focuses on eluxadoline, a novel pharmacological agent that has recently been approved by both the FDA and EMA for treatment of patients with IBS-D. Expert commentary: The efficacy and safety of eluxadoline in treating bowel habit alterations and pain, both in the short and long-term, make the drug a welcome addition to our therapeutic alternatives in IBS-D. Its positioning in any IBS algorithm will depend on the 'real world' prevalence of the small risk of sphincter of Oddi spasm and mild pancreatitis.

2 Review Progress with treating the microbial dysbiosis associated with irritable bowel syndrome. 2017

Pearson, James S / Whorwell, Peter J. ·aNeurogastroenterology Unit, University Hospital of South ManchesterbCentre for Digestive Diseases, University of Manchester, Manchester, UK. ·Curr Opin Gastroenterol · Pubmed #28134688.

ABSTRACT: PURPOSE OF REVIEW: Microbial dysbiosis is receiving increasing attention as possibly being important in the pathophysiology of irritable bowel syndrome. This review will summarize the most recent literature addressing attempts to explore and target the microbiome in patients with irritable bowel syndrome. RECENT FINDINGS: Manipulation of the intestinal microbiota in irritable bowel syndrome is receiving increasing attention. Traditionally, dietary manipulation has been utilized. There is now evidence that a low fermentable oligosaccharides, disaccharides, monosaccharides and polyols diet has not only been able to improve symptoms, but may have an effect on the gut microbiota. Probiotics are a safe and attractive option for the manipulation of the microbiota. There have been a number of well-designed trials examining the efficacy of certain strains of bacteria, and even yeasts are receiving attention. The role of antibiotics remains controversial and it seems likely that their use should currently be limited to those individuals with small intestinal bacterial overgrowth. Interest in the role of faecal microbiota transplantation for the treatment of a number of gastrointestinal conditions has intensified and irritable bowel syndrome is no exception. SUMMARY: The manipulation of the microbial dysbiosis is gaining momentum. Further research, however, is required in order to identify the most appropriate treatment option for each individual patient.

3 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 / Anonymous3490872. ·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).

4 Review Irritable bowel syndrome in adults in primary care: summary of updated NICE guidance. 2015

Hookway, Cheryl / Buckner, Sara / Crosland, Paul / Longson, Damien. ·National Institute for Health and Care Excellence, Clinical Guideline Updates Team, Manchester M1 4BT, UK cheryl.hookway@NICE.org.uk. · National Institute for Health and Care Excellence, Clinical Guideline Updates Team, London, UK. · Department of Psychiatry, Manchester Mental Health and Social Care Trust, Manchester, UK. ·BMJ · Pubmed #25716701.

ABSTRACT: -- No abstract --

5 Review Abdominal bloating and distension: what is the role of the microbiota. 2012

Issa, B / Wafaei, N A / Whorwell, P J. ·Neurogastroenterology Unit, Department of Translational Medicine, University of Manchester, Manchester, UK. ·Dig Dis Sci · Pubmed #21800157.

ABSTRACT: Most patients with irritable bowel syndrome complain of a sensation of an increase in pressure within their abdomen during the course of the day which is called bloating and, in approximately half of these individuals, this symptom is accompanied by an actual increase in abdominal girth, which is referred to as distension. The pathophysiology of these two phenomena is somewhat different and it is now recognised that a whole variety of overlapping mechanisms are involved. Some of these are potentially amenable to treatment by modification of the bacterial flora of the gut and this article reviews the evidence for this.

6 Review Imagery, colour and illness: a review. 2011

Carruthers, Helen R. ·Department of Medical Illustration, University Hospital of South Manchester NHS Foundation Trust, Manchester, UK. Helen.carruthers@uhsm.nhs.uk ·J Vis Commun Med · Pubmed #22023001.

ABSTRACT: This paper reviews research on the role of colour and imagery in relation to illness and examines how this might improve communication between the sufferer and those treating or caring for them. It describes a method by which colour can be related to situations such as an individual's mood and how this might be used to predict response to treatment. Furthermore, it provides evidence that documenting the imagery of an illness might give insight into the patients' fears and concerns about their condition as well as helping non-sufferers to understand what they are going through.

7 Review Emerging drugs for irritable bowel syndrome. 2009

Shekhar, Chander / Whorwell, Peter J. ·University of Manchester, Neurogastroenterology Unit, University Hospital of South Manchester NHS Trust, Manchester, M23 9LT, UK. peter.whorwell@UHSM.NHS.UK ·Expert Opin Emerg Drugs · Pubmed #19939211.

ABSTRACT: Irritable bowel syndrome is extremely common and its severity is widely underestimated. Unfortunately, the current pharmacological treatment of this condition is far from satisfactory which might suggest that it would be an area in which the pharmaceutical industry would take a great interest. However, drug development in this field, especially in relation to 5-hydroxytryptamine (5-HT), has been beset by difficulties with side effects and, what some authorities would claim, an unnecessarily strict regulatory climate based on the perception that irritable bowel syndrome is not a particularly serious condition. This has resulted in a rapid withdrawal from the scene by a number of companies although with the identification of some potential new therapeutic targets, the area has not been totally abandoned.

8 Review Hypnotherapy for functional gastrointestinal disorders: a review. 2009

Miller, Vivien / Whorwell, Peter J. ·University of Manchester, Manchester, United Kingdom. ·Int J Clin Exp Hypn · Pubmed #19459089.

ABSTRACT: Patients with functional gastrointestinal disorders, such as irritable bowel syndrome, functional dyspepsia, and noncardiac chest pain, can suffer from a range of severe symptoms that often substantially erode quality of life. Unfortunately, these conditions are notoriously difficult to treat, with many patients failing to improve despite being prescribed a wide variety of conventional medications. As a consequence, the potential benefits of hypnotherapy have been explored with evidence that this approach not only relieves symptoms but also appears to restore many of the putative psychological and physiological abnormalities associated with these conditions toward normal. These observations suggest that this form of treatment has considerable potential in aiding the management of functional gastrointestinal disorders and should be integrated into the ongoing medical care that these patients are receiving.

9 Review Hypnotherapy for irritable bowel syndrome: the response of colonic and noncolonic symptoms. 2008

Whorwell, Peter J. ·University of Manchester, Manchester, United Kingdom. peter.whorwell@manchseter.ac.uk ·J Psychosom Res · Pubmed #18501263.

ABSTRACT: There is now good evidence that hypnotherapy benefits a substantial proportion of patients with irritable bowel syndrome and that improvement is maintained for many years. Most patients seen in secondary care with this condition also suffer from a wide range of noncolonic symptoms such as backache and lethargy, as well as a number of musculoskeletal, urological, and gynaecological problems. These features do not typically respond well to conventional medical treatment approaches, but fortunately, their intensity is often reduced by hypnosis. The mechanisms by which hypnosis mediates its benefit are not entirely clear, but there is evidence that, in addition to its psychological effects, it can modulate gastrointestinal physiology, alter the central processing of noxious stimuli, and even influence immune function.

10 Article Efficacy of individual and group hypnotherapy in irritable bowel syndrome (IMAGINE): a multicentre randomised controlled trial. 2019

Flik, Carla E / Laan, Wijnand / Zuithoff, Nicolaas P A / van Rood, Yanda R / Smout, André J P M / Weusten, Bas L A M / Whorwell, Peter J / de Wit, Niek J. ·Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, Netherlands. Electronic address: c.e.flik@umcutrecht.nl. · Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, Netherlands. · Psychiatric Policlinic, Leiden University Medical Centre, Leiden, Netherlands. · Department of Gastroenterology and Hepatology, Academic Medical Centre, Amsterdam, Netherlands. · Department of Gastroenterology and Hepatology, University Medical Centre Utrecht, Utrecht, Netherlands; Department of Gastroenterology and Hepatology, St Antonius Hospital, Nieuwegein, Netherlands. · Education and Research Centre, Wythenshawe Hospital, Manchester, UK. ·Lancet Gastroenterol Hepatol · Pubmed #30473202.

ABSTRACT: BACKGROUND: Hypnotherapy for irritable bowel syndrome (IBS) has been used primarily in patients with refractory symptoms in specialised departments and delivered on an individual basis. We aimed to test the hypothesis that hypnotherapy would be more effective than educational supportive therapy, and that group hypnotherapy would be non-inferior to individual hypnotherapy for patients with IBS referred from primary and secondary care. METHODS: We did a multicentre randomised controlled trial (IMAGINE) in 11 hospitals in the Netherlands. Patients with IBS, aged 18-65 years, who were referred from primary or secondary care were randomly allocated (3:3:1) in blocks of six using a computer-based random number table procedure by staff not involved in the treatment to receive six sessions of individual or group hypnotherapy or group educational supportive therapy (control group). The primary outcome was adequate relief of IBS symptoms, with responders defined as patients who reported adequate relief when asked once weekly on three or four occasions in 4 consecutive weeks. We compared hypnotherapy (both groups) with control in the intention-to-treat population (excluding individuals subsequently found to be ineligible for enrolment), and assessed non-inferiority of group hypnotherapy versus individual hypnotherapy in the per-protocol population (with a non-inferiority margin of 15%) at 3 months and 12 months. This trial is registered with ISRCTN, number ISRCTN22888906, and is completed. FINDINGS: Between May 31, 2011, and April 6, 2016, 494 patients referred for psychological treatment for IBS were assessed for eligibility, of whom 354 were randomly allocated to the three groups: 150 to individual hypnotherapy, 150 to group hypnotherapy, and 54 to educational supportive therapy. After exclusion of individuals subsequently found to be ineligible for enrolment, 142 patients in the individual hypnotherapy group, 146 in the group hypnotherapy group, and 54 in the control group were included in the intention-to-treat population. Of these, 22 (15%) patients in the individual hypnotherapy group, 22 (15%) in the group hypnotherapy group, and 11 (20%) in the control group dropped out before or during therapy. In the intention-to-treat analysis, the adequate response rate was 40·8% (95% CI 31·7-50·5) in the individual hypnotherapy group, 33·2% (24·3-43·5) in the group hypnotherapy group, and 16·7% (7·6-32·6) in the control group at 3 months. At 12 months, 40·8% (31·3-51·1) of patients in the individual hypnotherapy group, 49·5% (38·8-60·0) of patients in the group hypnotherapy group, and 22.6% (11·5-39·5) of patients in the control group reported adequate relief. Hypnotherapy was more effective than control at 3 months (odds ratio 2·9, 95% CI 1·2-7·4, p=0·0240) and 12 months (2·8, 1·2-6·7, p=0·0185). In the per-protocol analysis, 49·9% (39·2-60·6) in the individual hypnotherapy group and 42·7% (32·3-53·8) in the group hypnotherapy group had adequate relief at 3 months, and 55·5% (43·4-67·1) of individual and 51·7% (40·2-63·0) of group hypnotherapy patients reported adequate relief at 12 months. Group hypnotherapy was therefore non-inferior to individual hypnotherapy. Eight unexpected serious adverse reactions (six in the individual hypnotherapy group and two in the group hypnotherapy group) were reported, most of which were cancer or inflammatory bowel disease, and were judged by the medical ethics committee as not being related to the therapy. INTERPRETATION: Hypnotherapy should be considered as a possible treatment for patients with IBS in primary and secondary care. Furthermore, group therapy could allow many more patients to be treated for the same cost. FUNDING: None.

11 Article Comorbidities in the diseasome are more apparent than real: What Bayesian filtering reveals about the comorbidities of depression. 2017

Marx, Peter / Antal, Peter / Bolgar, Bence / Bagdy, Gyorgy / Deakin, Bill / Juhasz, Gabriella. ·MTA-SE Neuropsychopharmacology and Neurochemistry Research Group, Hungarian Academy of Sciences, Semmelweis University, Budapest, Hungary. · Department of Measurement and Information Systems, Budapest University of Technology and Economics, Budapest, Hungary. · Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, Budapest, Hungary. · NAP-A-SE New Antidepressant Target Research Group, Hungarian Brain Research Program, Semmelweis University, Budapest, Hungary. · Neuroscience and Psychiatry Unit, School of Biological Sciences, Faculty of Biology Medicine and Health, The University of Manchester, Manchester, UK and Greater Manchester Mental Health NHS Foundation Trust, Manchester, UK. · MTA-SE-NAP B Genetic Brain Imaging Migraine Research Group, Hungarian Academy of Sciences, Semmelweis University, Budapest, Hungary. ·PLoS Comput Biol · Pubmed #28644851.

ABSTRACT: Comorbidity patterns have become a major source of information to explore shared mechanisms of pathogenesis between disorders. In hypothesis-free exploration of comorbid conditions, disease-disease networks are usually identified by pairwise methods. However, interpretation of the results is hindered by several confounders. In particular a very large number of pairwise associations can arise indirectly through other comorbidity associations and they increase exponentially with the increasing breadth of the investigated diseases. To investigate and filter this effect, we computed and compared pairwise approaches with a systems-based method, which constructs a sparse Bayesian direct multimorbidity map (BDMM) by systematically eliminating disease-mediated comorbidity relations. Additionally, focusing on depression-related parts of the BDMM, we evaluated correspondence with results from logistic regression, text-mining and molecular-level measures for comorbidities such as genetic overlap and the interactome-based association score. We used a subset of the UK Biobank Resource, a cross-sectional dataset including 247 diseases and 117,392 participants who filled out a detailed questionnaire about mental health. The sparse comorbidity map confirmed that depressed patients frequently suffer from both psychiatric and somatic comorbid disorders. Notably, anxiety and obesity show strong and direct relationships with depression. The BDMM identified further directly co-morbid somatic disorders, e.g. irritable bowel syndrome, fibromyalgia, or migraine. Using the subnetwork of depression and metabolic disorders for functional analysis, the interactome-based system-level score showed the best agreement with the sparse disease network. This indicates that these epidemiologically strong disease-disease relations have improved correspondence with expected molecular-level mechanisms. The substantially fewer number of comorbidity relations in the BDMM compared to pairwise methods implies that biologically meaningful comorbid relations may be less frequent than earlier pairwise methods suggested. The computed interactive comprehensive multimorbidity views over the diseasome are available on the web at Co=MorNet: bioinformatics.mit.bme.hu/UKBNetworks.

12 Article 'Holiday sickness'-reported exploratory outcome of over 500 United Kingdom holidaymakers with travellers' diarrhoea. 2017

Sheen, Prof Aali J / Zahid, M Saad B / Fagbemi, Andrew / Fullwood, Catherine / Whitehead, Kathryn. ·Department of Surgery, Central Manchester NHS Foundation Trust, Oxford Road, Manchester, UK aali.sheen@cmft.nhs.uk. · Department of Microbiology Research, School of Healthcare Sciences, Manchester Metropolitan University, Manchester, UK. · Department of Surgery, Central Manchester NHS Foundation Trust, Oxford Road, Manchester, UK. · Department of Paediatric Gastroenterology, Central Manchester NHS Foundation Trust, Oxford Road, Manchester, UK. · Centre for Biostatistics, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK. · Research & Innovation, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Sciences Centre, Manchester, UK. ·J Travel Med · Pubmed #28077608.

ABSTRACT: AIMS: To ascertain any predictors of potential food poisoning pathogens and development of post-infective irritable bowel syndrome (IBS) in UK travellers. An analysis was undertaken on prospectively collected data on 527 patients reporting symptoms of suspected food poisoning between June 2012 and June 2015. MAIN OUTCOME MEASURES: Positive stool sample indicative of food poisoning pathogens and diagnosis of post-infective IBS. RESULTS: Data on 527 patients were examined. The large majority of patients did not provide a stool sample on return from holiday (n = 430, 81.6%) as few visited a Doctor locally or in the UK. Only 18 patients (18.6%, 95% confidence interval [CI] 11.4-27.7) who provided a stool sample were positive for microbiological food poisoning pathogens. Univariate analysis indicated a significant relationship between a positive stool sample and whether the individual sought any medical assistance at the resort (odds ratio [OR] 0.24, 95% CI 0.08-0.70) and whether they took any treatment (including self-medicated), (OR 0.21, 95% CI 0.06-0.67). Of the 527 patients only 30 (5.7%, 95% CI 3.9-8.1) experienced post-infective IBS. Univariate regression indicated a significant relationship between experiencing Per Rectal (PR) bleeding and a diagnosis of post-infective IBS (OR 3.64, 95% CI 1.00-10.49). Univariate regression also indicated an increase in the risk of developing post-infective IBS with increasing duration of symptoms (OR 1.04, 95% CI 1.02-1.05). No significant relationship was found between a positive stool sample and developing post-infective IBS (P = 0.307). CONCLUSIONS: Very few patients provide a stool sample after experiencing holiday sickness abroad. Of those that do, only a small proportion have a positive stool sample indicative of a food poisoning microorganism. Around 6% of individuals were diagnosed with post-infective IBS. Those individuals with PR bleeding and symptoms persisting for longer durations were significantly more at risk of developing post-infective IBS, whilst medical aid and treatment abroad was found to reduce the odds of a positive stool sample.

13 Article A mechanistic multicentre, parallel group, randomised placebo-controlled trial of mesalazine for the treatment of IBS with diarrhoea (IBS-D). 2016

Lam, Ching / Tan, Wei / Leighton, Matthew / Hastings, Margaret / Lingaya, Melanie / Falcone, Yirga / Zhou, Xiaoying / Xu, Luting / Whorwell, Peter / Walls, Andrew F / Zaitoun, Abed / Montgomery, Alan / Spiller, Robin. ·NIHR Nottingham Digestive Diseases Biomedical Research Unit, University of Nottingham, Nottingham, UK. · Nottingham Clinical Trials Unit, University of Nottingham, Nottingham, UK. · Neurogastroenterology Unit, Wythenshawe Hospital, Manchester, UK. · Immunopharmacology Group, University of Southampton, Southampton General Hospital, Southampton, UK. · FRAME laboratory, University of Nottingham, Nottingham, UK. · Department of Histopathology, Nottingham University Hospital Trusts, Nottingham, UK. ·Gut · Pubmed #25765462.

ABSTRACT: INTRODUCTION: Immune activation has been reported in the mucosa of IBS patients with diarrhoea (IBS-D), and some small studies have suggested that mesalazine may reduce symptoms. We performed a double-blind, randomised placebo-controlled trial of 2 g mesalazine twice daily versus placebo for 3 months in patients with Rome III criteria IBS-D. Primary outcome was daily average stool frequency during weeks 11-12; secondary outcomes were abdominal pain, stool consistency, urgency and satisfactory relief of IBS symptoms. METHODS: Participants were randomised after a 2-week baseline stool diary. All participants completed a 12-week stool diary and at the end of each week recorded the presence of 'satisfactory relief of IBS symptoms'. RESULTS: 136 patients with IBS-D (82 women, 54 men) were randomised, 10 patients withdrew from each group. Analysis by intention to treat showed the daily average stool frequency during weeks 11 and 12 were mean (SD), 2.8 (1.2) in mesalazine and 2.7 (1.9) in the placebo group with no significant group difference, (95% CI) 0.1 (-0.33 to 0.53), p=0.66. Mesalazine did not improve abdominal pain, stool consistency nor percentage with satisfactory relief compared with placebo during the last two-weeks follow-up. CONCLUSIONS: This study does not support any clinically meaningful benefit or harm of mesalazine compared with placebo in unselected patients with IBS-D. More precise subtyping based on underlying disease mechanisms is needed to allow more effective targeting of treatment in IBS. TRIAL REGISTRATION NUMBER: NCT01316718.

14 Article No association between the common calcium-sensing receptor polymorphism rs1801725 and irritable bowel syndrome. 2015

Romero, Philipp / Schmitteckert, Stefanie / Wouters, Mira M / Houghton, Lesley A / Czogalla, Bastian / Sayuk, Gregory S / Boeckxstaens, Guy E / Guenther, Patrick / Holland-Cunz, Stefan / Niesler, Beate. ·Department of Surgery, Division of Paediatric Surgery, University of Heidelberg, Heidelberg, Germany. Philipp.Romero@med.uni-heidelberg.de. · Department of Human Molecular Genetics, Institute of Human Genetics, University of Heidelberg, Im Neuenheimer Feld 366, Heidelberg, 69120, Germany. S.Schmitteckert@med.uni-heidelberg.de. · TARGID, University Hospital Leuven, Leuven, Belgium. mira.wouters@med.kuleuven.be. · University of Manchester, Manchester, UK & Mayo Clinic, Jacksonville, USA. Houghton.Lesley@mayo.edu. · Department of Human Molecular Genetics, Institute of Human Genetics, University of Heidelberg, Im Neuenheimer Feld 366, Heidelberg, 69120, Germany. bastian.czogalla@med.uni-heidelberg.de. · Washington University School of Medicine, St. Louis, USA. gsayuk@dom.wustl.edu. · TARGID, University Hospital Leuven, Leuven, Belgium. guy.boeckxstaens@med.kuleiven.be. · Department of Surgery, Division of Paediatric Surgery, University of Heidelberg, Heidelberg, Germany. Patrick.Guenther@med.uni-heidelberg.de. · Department of Paediatric Surgery, University of Basel, Basel, Switzerland. Stefan.Holland-Cunz@ukbb.ch. · Department of Human Molecular Genetics, Institute of Human Genetics, University of Heidelberg, Im Neuenheimer Feld 366, Heidelberg, 69120, Germany. Beate.Niesler@med.uni-heidelberg.de. ·BMC Med Genet · Pubmed #26654249.

ABSTRACT: BACKGROUND: The calcium-sensing receptor (CaSR) is a calcium (Ca(2+)) sensitive G protein-coupled receptor implicated in various biological processes. In particular, it regulates Ca(2+)/Mg(2+)- homeostasis and senses interstitial Ca(2+) levels and thereby controls downstream signalling cascades. Due to its expression in the gut epithelium, the enteric nervous system and smooth muscles and its key function in regulation and coordination of muscular contraction and secretion, it represents an excellent candidate gene to be investigated in the pathophysiology of irritable bowel syndrome (IBS). Disturbed CaSR structure and function may impact gastrointestinal regulation of muscular contraction, neuronal excitation and secretion and consequently contribute to symptoms seen in IBS, such as disordered defecation as well as disturbed gut motility and visceral sensitivity. METHODS: We have therefore genotyped the functional CASR SNP rs1801725 in three case control samples from the UK, Belgium and the USA. RESULTS: Genotype frequencies showed no association in the three genotyped case-control samples, neither with IBS nor with IBS subtypes. CONCLUSIONS: Although we could not associate the SNP to any of the established bowel symptom based IBS subtypes we cannot rule out association to altered Ca(2+) levels and disturbed secretion and gut motility which were unfortunately not assessed in the patients genotyped. This underlines the necessity of a more detailed phenotyping of IBS patients and control individuals in future studies.

15 Article Modulation of human visceral sensitivity by noninvasive magnetoelectrical neural stimulation in health and irritable bowel syndrome. 2015

Algladi, Tarig / Harris, Mary / Whorwell, Peter J / Paine, Peter / Hamdy, Shaheen. ·aCentre for Gastrointestinal Sciences, Institute of Inflammation and Repair, Faculty of Medical and Human Sciences, University of Manchester, Manchester, United Kingdom bDepartment of Gastroenterology, Salford Royal Hospital NHS Trust, Salford, United Kingdom. ·Pain · Pubmed #25867123.

ABSTRACT: Visceral pain is a particularly difficult symptom to manage in patients with irritable bowel syndrome (IBS). Our aim was to examine whether noninvasive neurostimulation applied to the motor cortex or lumbosacral region can modulate human visceral sensation. Sixteen healthy adult volunteers and 10 patients with IBS were evaluated. Single-pulse lumbosacral magnetic stimulation (LSMS) or transcranial magnetic stimulation (TMS) was used to assess spinal root and cortical excitability as well as the effect of neurostimulation on anorectal sensation and pain, which were provoked by a local electrical stimulus. Initially, healthy volunteers received 6 stimulation paradigms in a randomised order (3 repetitive LSMS [1 Hz, 10 Hz, and sham]) and 3 repetitive TMS (1 Hz, 10 Hz, and sham) to investigate the effects on neural function and visceral sensation over 1 hour. The most effective cortical and spinal interventions were then applied in patients with IBS. Only 1-Hz rLSMS altered healthy anal motor excitability, increasing spinal (58 ± 12.3 vs 38.5 ± 5.7 μV, P = 0.04) but not cortical responses. Both 1-Hz rLSMS and 10-Hz repetitive transcranial magnetic stimulation increased healthy rectal pain thresholds for up to an hour after intervention (P < 0.05). When applied to patients with IBS, rectal pain thresholds were increased across all time points after both 1-Hz rLSMS and 10-Hz repetitive transcranial magnetic stimulation (P < 0.05) compared with sham. The application of magnetoelectric stimuli to the cortical and lumbosacral areas modulates visceral sensation in healthy subjects and patients with IBS. This proof-of-concept study provides supportive evidence for neurostimulation in managing functional gastrointestinal disorders.

16 Article The Intestinal Gas Questionnaire: development of a new instrument for measuring gas-related symptoms and their impact on daily life. 2015

Chassany, O / Tugaut, B / Marrel, A / Guyonnet, D / Arbuckle, R / Duracinsky, M / Whorwell, P J / Azpiroz, F. ·Patient-Centered Outcomes Research, EA 7334, University Paris-Diderot, Paris, France. · Health Economics Clinical Research Unit, Hotel-Dieu hospital, AP-HP, Paris, France. · HEOR & Strategic Market Access, Mapi, Lyon, France. · Danone Nutricia Research, Palaiseau, France. · Endpoint Development and Outcomes Assessment, Adelphi Values, Manchester, UK. · Internal Medicine & Clinical Immunology Department, Bicêtre Hospital, AP-HP, Kremlin-Bicêtre, France. · Wythenshawe Hospital, Manchester, UK. · Digestive System Research Unit, University Hospital Vall d'Hebron, Barcelona, Spain. · Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Spain. · Department of Medicine, Universitat Autónoma de Barcelona, Spain. ·Neurogastroenterol Motil · Pubmed #25846412.

ABSTRACT: BACKGROUND: Although gas-related symptoms (GRS) are common and intrusive, there are no questionnaires to quantitate this problem. This study aimed to develop an instrument to rectify this gap in our knowledge. METHODS: Concepts were initially identified from the literature and interviews with gastroenterologists. Exploratory one-to-one interviews and focus groups with irritable bowel syndrome (IBS) patients (n = 28) and non-IBS subjects (n = 27) with GRS were conducted in UK, France, and Spain leading to a conceptual framework for the questionnaire. Last, iterative rounds of cognitive debriefing were performed with IBS (n = 16) and non-IBS subjects (n = 14). KEY RESULTS: From the first three steps, nine GRS (bloating, distension, flatulence, odorous flatulence, difficult gas evacuation, stomach rumbling, belching, bad breath, and abdominal movement) were identified although abdominal movement was subsequently excluded. Twelve quality of life domains affected by these symptoms were identified as: Clothing, emotional, physical appearance, diet, daily living, work, social life, physical activity, relationships, sex life, sleep, and cognitive function. A 24-h recall for symptoms and a 7-day recall for impact assessment were supported by the qualitative findings. Cognitive debriefing confirmed the understanding of the instrument. Across the three languages, the instrument was conceptually and linguistically consistent. CONCLUSIONS & INFERENCES: The International Gas Questionnaire is a 2-part instrument, developed rigorously and simultaneously in three languages assessing seven symptoms (17 items) and their impact on 12 domains (26 items) in IBS and general population. It is now undergoing psychometric validation and should provide a unique tool for epidemiological surveys and clinical trials for developing new treatments for these symptoms.

17 Article Hypnotherapy for irritable bowel syndrome: an audit of one thousand adult patients. 2015

Miller, V / Carruthers, H R / Morris, J / Hasan, S S / Archbold, S / Whorwell, P J. ·Neurogastroenterology Unit, Wythenshawe Hospital, Manchester, UK. ·Aliment Pharmacol Ther · Pubmed #25736234.

ABSTRACT: BACKGROUND: Gut-focused hypnotherapy improves the symptoms of irritable bowel syndrome (IBS) with benefits being sustained for many years. Despite this, the technique has not been widely adopted by healthcare systems, possibly due to relatively small numbers in published studies and uncertainty about how it should be provided. AIM: To review the effect of hypnotherapy in a large cohort of refractory IBS patients. METHODS: One thousand IBS patients fulfilling Rome II criteria, mean age 51.6 years (range 17-91 years), 80% female, receiving 12 sessions of hypnotherapy over 3 months, were studied. The primary outcome was a 50 point reduction in the IBS Symptom Severity Score. The fall in scores for Noncolonic Symptoms, Quality of Life and Anxiety or Depression, were secondary outcomes. The Federal Drug Administration's recommended outcome of a 30% or more reduction in abdominal pain was also recorded. RESULTS: Overall, 76% met the primary outcome which was higher in females (females: 80%, males: 62%, P < 0.001) and those with anxiety (anxious: 79%, non-anxious: 71%, P = 0.010). The mean reduction in other scores was: IBS Symptom Severity Score, 129 points (P < 0.001), Noncolonic Symptom Score, 65 (P < 0.001) and Quality of Life Score, 66 (P < 0.001). Sixty-seven per cent reported a 30% or more reduction in abdominal pain scores. Pain days fell from 18 to 9 per month. Patients with anxiety and depression fell from 63% to 34% and 25% to 12% respectively (P < 0.001). Outcome was unaffected by bowel habit subtype. CONCLUSION: These results provide further evidence that gut-focused hypnotherapy is an effective intervention for refractory IBS.

18 Article Exploring the genetics of irritable bowel syndrome: a GWA study in the general population and replication in multinational case-control cohorts. 2015

Ek, Weronica E / Reznichenko, Anna / Ripke, Stephan / Niesler, Beate / Zucchelli, Marco / Rivera, Natalia V / Schmidt, Peter T / Pedersen, Nancy L / Magnusson, Patrik / Talley, Nicholas J / Holliday, Elizabeth G / Houghton, Lesley / Gazouli, Maria / Karamanolis, George / Rappold, Gudrun / Burwinkel, Barbara / Surowy, Harald / Rafter, Joseph / Assadi, Ghazaleh / Li, Ling / Papadaki, Evangelia / Gambaccini, Dario / Marchi, Santino / Colucci, Rocchina / Blandizzi, Corrado / Barbaro, Raffaella / Karling, Pontus / Walter, Susanna / Ohlsson, Bodil / Tornblom, Hans / Bresso, Francesca / Andreasson, Anna / Dlugosz, Aldona / Simren, Magnus / Agreus, Lars / Lindberg, Greger / Boeckxstaens, Guy / Bellini, Massimo / Stanghellini, Vincenzo / Barbara, Giovanni / Daly, Mark J / Camilleri, Michael / Wouters, Mira M / D'Amato, Mauro. ·Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden. · Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. · Department of Human Molecular Genetics, Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany. · Department of Gastroenterology and Hepatology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden. · Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. · Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia. · Faculty of Medical and Human Sciences, Institute of Inflammation and Repair, University of Manchester, Manchester, UK Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA. · Laboratory of Biology, School of Medicine, University of Athens, Athens, Greece. · Academic Department of Gastroenterology, School of Medicine, University of Athens, Athens, Greece. · Molecular Epidemiology Group, German Cancer Research Centre (DKFZ) Heidelberg, Heidelberg, Germany Division of Molecular Biology of Breast Cancer, Department of Gynaecology and Obstetrics, University Women's Clinic, University Heidelberg, Heidelberg, Germany. · Gastroenterology Unit, Department of Gastroenterology, University of Pisa, Pisa, Italy. · Division of Pharmacology and Chemotherapy, Department of Clinical and Experimental Medicine University of Pisa, Pisa, Italy. · Department of Medical and Surgical Sciences, University of Bologna, St. Orsola-Malpighi Hospital, Bologna, Italy. · Department of Medicine, Umeå, University, Umeå, Sweden. · Division of Gastroenterology, Institution of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden. · Department of Clinical Sciences, Skånes University Hospital, Malmoe, Sweden. · Department of Internal Medicine & Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. · Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden Department of Gastroenterology and Hepatology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden. · Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden Stress Research Institute, Stockholm University, Stockholm, Sweden. · Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden. · Translational Research Center for Gastrointestinal Disorders, Leuven University, Leuven, Belgium. · Clinical Enteric Neuroscience Translational and Epidemiological Research, Mayo Clinic, Rochester, Minnesota, USA. ·Gut · Pubmed #25248455.

ABSTRACT: OBJECTIVE: IBS shows genetic predisposition, but adequately powered gene-hunting efforts have been scarce so far. We sought to identify true IBS genetic risk factors by means of genome-wide association (GWA) and independent replication studies. DESIGN: We conducted a GWA study (GWAS) of IBS in a general population sample of 11,326 Swedish twins. IBS cases (N=534) and asymptomatic controls (N=4932) were identified based on questionnaire data. Suggestive association signals were followed-up in 3511 individuals from six case-control cohorts. We sought genotype-gene expression correlations through single nucleotide polymorphism (SNP)-expression quantitative trait loci interactions testing, and performed in silico prediction of gene function. We compared candidate gene expression by real-time qPCR in rectal mucosal biopsies of patients with IBS and controls. RESULTS: One locus at 7p22.1, which includes the genes KDELR2 (KDEL endoplasmic reticulum protein retention receptor 2) and GRID2IP (glutamate receptor, ionotropic, delta 2 (Grid2) interacting protein), showed consistent IBS risk effects in the index GWAS and all replication cohorts and reached p=9.31×10(-6) in a meta-analysis of all datasets. Several SNPs in this region are associated with cis effects on KDELR2 expression, and a trend for increased mucosal KDLER2 mRNA expression was observed in IBS cases compared with controls. CONCLUSIONS: Our results demonstrate that general population-based studies combined with analyses of patient cohorts provide good opportunities for gene discovery in IBS. The 7p22.1 and other risk signals detected in this study constitute a good starting platform for hypothesis testing in future functional investigations.

19 Article Irritable bowel syndrome: a comparison of subtypes. 2015

Rey de Castro, Nicolas G / Miller, Vivien / Carruthers, Helen R / Whorwell, Peter J. ·Centre for Gastrointestinal Sciences, Institute of Inflammation and Repair, University of Manchester, Manchester, UK. ·J Gastroenterol Hepatol · Pubmed #25091059.

ABSTRACT: BACKGROUND AND AIM: Irritable bowel syndrome (IBS) is traditionally divided into subtypes depending on the bowel habit abnormality, but there is little clarity in the literature about whether these subtypes differ symptomatically or psychologically. Furthermore, there are conflicting reports on the relationship between symptom severity and psychological status. The aim of this study was to address these issues in a large cohort of patients defined by bowel habit. METHODS: One thousand IBS patients were divided into diarrhea (IBS-D), constipation (IBS-C), and mixed (IBS-M) bowel habit subtypes and completed a series of validated questionnaires capturing symptom severity, non-colonic symptomatology (somatization), quality of life, and anxiety or depression levels. Comparisons were made using SPSS version 20. RESULTS: There were no significant differences between the three subtypes with respect to symptom severity, abdominal pain intensity, non-colonic symptomatology, quality of life, and anxiety or depression scores (all Ps > 0.05). In addition, there was only a small but statistically significant correlation between IBS symptom severity and both anxiety or depression, as well as quality of life (highest r = 0.34), while the relationship between somatization and disease severity was moderate (r = 0.42). CONCLUSION: This study suggests that there are no differences in the symptom profiles and anxiety or depression scores between different subtypes of IBS. In addition, anxiety and depression do not appear to be strongly associated with symptom severity, although this does not exclude the possible interplay between these and other psychological drivers of severity, such as poor coping skills.

20 Article Functioning of the hypothalamic-pituitary-adrenal and growth hormone axes in frequently unexplained disorders: results of a population study. 2014

Aggarwal, V R / Macfarlane, G J / Tajar, A / Mulvey, M R / Power, A / Ray, D / McBeth, J. ·School of Dentistry, Manchester Biomedical Research Centre, University of Manchester, UK. ·Eur J Pain · Pubmed #25764228.

ABSTRACT: BACKGROUND: The aim of the study was to test the hypothesis that associations with specific stress systems [hypothalamic-pituitary-adrenal (HPA) and growth hormone (GH) axes] would increase as the number of unexplained disorders increased while accounting for the possible confounding effects of psychosocial factors. METHODS: A cross-sectional study identified those reporting chronic widespread pain, irritable bowel syndrome, chronic orofacial pain and chronic fatigue. Of the 1315 subjects, disorder status was available for 1180 (89.7%), of whom 766 (64.9%) reported no disorders, 277 (23.5%) reported one and 137 (11.6%) reported two or more. Eighty subjects were sought from each group for assessment of HPA (morning 8:00 a.m. and evening 10:00 p.m. saliva, and post-dexamethasone serum cortisol levels) and GH [serum insulin-like growth factor 1 (IGF-1) level] axis function. Validated questionnaires informed current psychological state. RESULTS: Two hundred twenty-seven subjects participated [79 (35%) with no disorders, 78 (34%) with one disorder and 70 (31%) with two or more disorders]. There were no significant associations (p < 0.05) between individual disorders or an increasing disorder load with any of the neuroendocrine levels measured: saliva/serum cortisol, IGF-1 and dehydroepiandrosterone. Psychosocial factors were independently associated with disorders and with an increasing disorder load: health anxiety p < 0.01, anxiety p < 0.01, depression p < 0.01, life events p = 0.03. CONCLUSION: Although previous studies have shown that stress axis function acts to moderate the risk of onset of some of these disorders, the present study shows that the degree of dysfunction is not correlated with a corresponding increasing load of disorders. The uncertainty surrounding the role of these biomarkers in the aetiology of unexplained disorders needs further investigation.

21 Article Changes of the human gut microbiome induced by a fermented milk product. 2014

Veiga, Patrick / Pons, Nicolas / Agrawal, Anurag / Oozeer, Raish / Guyonnet, Denis / Brazeilles, Rémi / Faurie, Jean-Michel / van Hylckama Vlieg, Johan E T / Houghton, Lesley A / Whorwell, Peter J / Ehrlich, S Dusko / Kennedy, Sean P. ·Danone Nutricia Research, Palaiseau, France. · INRA, Metagenopolis, Jouy-en-Josas, France. · Neurogastroenterology Unit, University of Manchester, Manchester, United Kingdom. · C2R, Paris, France. · 1] Centre for Gastrointestinal Sciences, University of Manchester, University Hospital of South Manchester, Manchester, United Kingdom [2] Division of Gastroenterology and Hepatology, Mayo Clinic, Florida, USA. · Centre for Gastrointestinal Sciences, University of Manchester, University Hospital of South Manchester, Manchester, United Kingdom. · 1] INRA, Metagenopolis, Jouy-en-Josas, France [2] Centre for Human Microbiome Interactions, King's College London, London, United Kingdom. ·Sci Rep · Pubmed #25209713.

ABSTRACT: The gut microbiota (GM) consists of resident commensals and transient microbes conveyed by the diet but little is known about the role of the latter on GM homeostasis. Here we show, by a conjunction of quantitative metagenomics, in silico genome reconstruction and metabolic modeling, that consumption of a fermented milk product containing dairy starters and Bifidobacterium animalis potentiates colonic short chain fatty acids production and decreases abundance of a pathobiont Bilophila wadsworthia compared to a milk product in subjects with irritable bowel syndrome (IBS, n = 28). The GM changes parallel improvement of IBS state, suggesting a role of the fermented milk bacteria in gut homeostasis. Our data challenge the view that microbes ingested with food have little impact on the human GM functioning and rather provide support for beneficial health effects.

22 Article A randomised trial of ondansetron for the treatment of irritable bowel syndrome with diarrhoea. 2014

Garsed, Klara / Chernova, Julia / Hastings, Margaret / Lam, Ching / Marciani, Luca / Singh, Gulzar / Henry, Amanda / Hall, Ian / Whorwell, Peter / Spiller, Robin. ·Nottingham Digestive Diseases Biomedical Research Unit, Queens Medical Centre, Nottingham, UK. · Neurogastroenterology Unit, Wythenshawe Hospital, Manchester, UK. · Sir Peter Mansfield Magnetic Resonance Imaging Centre, University of Nottingham, Nottingham, UK. · Department of Molecular Medicine, School of Surgical and Medical Sciences, University of Nottingham, Nottingham, UK. ·Gut · Pubmed #24334242.

ABSTRACT: BACKGROUND: Irritable bowel syndrome with diarrhoea (IBS-D) is particularly debilitating due to urgency and episodic incontinence. Some 5-hydroxytryptamine 3 (5-HT3) receptor antagonists (5-HT3RAs) have proven effective but have serious side effects. Ondansetron, also a 5-HT3RA, has been widely used as an antiemetic with an excellent safety record for over two decades. Our aim was to assess its effectiveness in IBS-D. METHODS: 120 patients meeting Rome III criteria for IBS-D entered a randomised, double-blind, placebo-controlled crossover study of 5 weeks of ondansetron 4 mg versus placebo with dose titration allowed, up to two tablets three times daily in the first 3 weeks. Patients completed daily diaries documenting stool consistency using the Bristol Stool Form score. Gut transit was measured in the last week of each treatment. The primary endpoint was average stool consistency in the last 2 weeks of treatment. RESULTS: Ondansetron significantly improved stool consistency (mean difference in stool form between ondansetron and placebo -0.9, 95% CI -1.1 to -0.6, p<0.001). Compared with placebo, patients on ondansetron experienced fewer days with urgency (p<0.001), lower urgency scores (p<0.001), reduced frequency of defaecation (p=0.002) and less bloating (p=0.002), although pain scores did not change significantly. IBS symptom severity score fell more with ondansetron than placebo (83±9.8 vs 37±9.7, p=0.001). 65% reported adequate relief with ondansetron but not placebo compared with 14% reporting relief with placebo but not ondansetron, relative risk 4.7, 95% CI 2.6 to 8.5, p<0.001. CONCLUSIONS: Ondansetron relieves some of the most intrusive symptoms of IBS-D, namely loose stools, frequency and urgency.

23 Article Genetic variants in CDC42 and NXPH1 as susceptibility factors for constipation and diarrhoea predominant irritable bowel syndrome. 2014

Wouters, Mira M / Lambrechts, Diether / Knapp, Michael / Cleynen, Isabelle / Whorwell, Peter / Agréus, Lars / Dlugosz, Aldona / Schmidt, Peter Thelin / Halfvarson, Jonas / Simrén, Magnus / Ohlsson, Bodil / Karling, Pontus / Van Wanrooy, Sander / Mondelaers, Stéphanie / Vermeire, Severine / Lindberg, Greger / Spiller, Robin / Dukes, George / D'Amato, Mauro / Boeckxstaens, Guy. ·Translational Research Center for Gastrointestinal Disorders, Leuven University, Leuven, Belgium. · Vesalius Research Center, VIB, Leuven University, Leuven, Belgium Laboratory for Translational Genetics, Department of Oncology, Leuven University, Leuven, Belgium. · Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany. · Department of Medicine, University of Manchester, Manchester, UK. · Centre for Family Medicine, Karolinska Institutet, Stockholm, Sweden. · Department of Medicine, Karolinska Institutet, Stockholm, Sweden. · Department of Internal Medicine, Örebro University Hospital, Örebro, Sweden. · Department of Internal Medicine, Gothenburg University, Gothenburg, Sweden. · Department of Clinical Sciences, Skånes University Hospital, Malmoe, Sweden. · Department of Medicine, Umeå University, Umeå, Sweden. · Queen's Medical Centre, Nottingham, UK. · Academic DPU, GlaxoSmithKline, Research Triangle Par, North Carolina, USA. · Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden. ·Gut · Pubmed #24041540.

ABSTRACT: OBJECTIVE: The complex genetic aetiology underlying irritable bowel syndrome (IBS) needs to be assessed in large-scale genetic studies. Two independent IBS cohorts were genotyped to assess whether genetic variability in immune, neuronal and barrier integrity genes is associated with IBS. DESIGN: 384 single nucleotide polymorphisms (SNPs) covering 270 genes were genotyped in an exploratory cohort (935 IBS patients, 639 controls). 33 SNPs with Puncorrected<0.05 were validated in an independent set of 497 patients and 887 controls. Genotype distributions of single SNPs were assessed using an additive genetic model in IBS and clinical subtypes, IBS-C and IBS-D, both in individual and combined cohorts. Trait anxiety (N=614 patients, 533 controls), lifetime depression (N=654 patients, 533 controls) and mRNA expression in rectal biopsies (N=22 patients, 29 controls) were correlated with SNP genotypes. RESULTS: Two SNPs associated independently in the exploratory and validation cohort: rs17837965-CDC42 with IBS-C (ORexploratory=1.59 (1.05 to 1.76); ORvalidation=1.76 (1.03 to 3.01)) and rs2349775-NXPH1 with IBS-D (ORexploratory=1.28 (1.06 to 1.56); ORvalidation=1.42 (1.08 to 1.88)). When combining both cohorts, the association of rs2349775 withstood post hoc correction for multiple testing in the IBS-D subgroup. Additionally, three SNPs in immune-related genes (rs1464510-LPP, rs1881457-IL13, rs2104286-IL2RA), one SNP in a neuronal gene (rs2349775-NXPH1) and two SNPs in epithelial genes (rs245051-SLC26A2, rs17837965-CDC42) were weakly associated with total-IBS (Puncorrected<0.05). At the functional level, rs1881457 increased IL13 mRNA levels, whereas anxiety and depression scores did not correlate with rs2349775-NXPH1. CONCLUSIONS: Rs2349775 (NXPH1) and rs17837965 (CDC42) were associated with IBS-D and IBS-C, respectively, in two independent cohorts. Further studies are warranted to validate our findings and to determine the mechanisms underlying IBS pathophysiology.

24 Article Using read codes to identify patients with irritable bowel syndrome in general practice: a database study. 2013

Harkness, Elaine F / Grant, Laura / O'Brien, Sarah J / Chew-Graham, Carolyn A / Thompson, David G. ·Institute of Inflammation and Repair, Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PL, UK. Elaine.F.Harkness@manchester.ac.uk. ·BMC Fam Pract · Pubmed #24295337.

ABSTRACT: BACKGROUND: Estimates of the prevalence of irritable bowel syndrome (IBS) vary widely, and a large proportion of patients report having consulted their general practitioner (GP). In patients with new onset gastrointestinal symptoms in primary care it might be possible to predict those at risk of persistent symptoms. However, one of the difficulties is identifying patients within primary care. GPs use a variety of Read Codes to describe patients presenting with IBS. Furthermore, in a qualitative study, exploring GPs' attitudes and approaches to defining patients with IBS, GPs appeared reluctant to add the IBS Read Code to the patient record until more serious conditions were ruled out. Consequently, symptom codes such as 'abdominal pain', 'diarrhoea' or 'constipation' are used. The aim of the current study was to investigate the prevalence of recorded consultations for IBS and to explore the symptom profile of patients with IBS using data from the Salford Integrated Record (SIR). METHODS: This was a database study using the SIR, a local patient sharing record system integrating primary, community and secondary care information. Records were obtained for a cohort of patients with gastrointestinal disorders from January 2002 to December 2011. Prevalence rates, symptom recording, medication prescribing and referral patterns were compared for three patient groups (IBS, abdominal pain (AP) and Inflammatory Bowel Disease (IBD)). RESULTS: The prevalence of IBS (age standardised rate: 616 per year per 100,000 population) was much lower than expected compared with that reported in the literature. The majority of patients (69%) had no gastrointestinal symptoms recorded in the year prior to their IBS. However a proportion of these (22%) were likely to have been prescribed NICE guideline recommended medications for IBS in that year. The findings for AP and IBD were similar. CONCLUSIONS: Using Read Codes to identify patients with IBS may lead to a large underestimate of the community prevalence. The IBS diagnostic Read Code was rarely applied in practice. There are similarities with many other medically unexplained symptoms which are typically difficult to diagnose in clinical practice.

25 Article Rome III functional constipation and irritable bowel syndrome with constipation are similar disorders within a spectrum of sensitization, regulated by serotonin. 2013

Shekhar, Chander / Monaghan, Phillip J / Morris, Julie / Issa, Basma / Whorwell, Peter J / Keevil, Brian / Houghton, Lesley A. ·Neurogastroenterology Unit, University of Manchester, Manchester, UK. ·Gastroenterology · Pubmed #23872499.

ABSTRACT: BACKGROUND & AIMS: Patients with irritable bowel syndrome with constipation (IBS-C) and patients with functional constipation (FC) have similar symptoms, and these disorders overlap in their diagnostic features. Little is known about their overlap in physiology or the involvement of serotonin signaling. We investigated relationships between platelet-depleted plasma concentrations of serotonin, gastrointestinal symptoms, and motor-sensory function in patients with FC or IBS-C compared with healthy volunteers (controls). METHODS: We measured platelet-depleted plasma concentrations of serotonin in fasting and fed individuals with IBS-C (n = 23; 19-50 years old), FC (n = 11; 25-46 years old), and controls (n = 23; 20-49 years old) recruited in Manchester, UK. We also quantified abdominal and bowel-related symptoms, rectal sensitivity, oro-cecal transit, and colonic (whole intestine) transit. RESULTS: Patients with IBS-C or FC had similar baseline symptoms, bowel habits, oro-cecal and colonic transit, and fasting concentrations of serotonin and response to meal ingestion. Only patients with IBS-C had increased symptoms after ingestion of a meal (P < .001)-these patients tended to have lower sensory thresholds than patients with FC. Defecation frequency in the combined group of patients with IBS-C or FC correlated inversely with serotonin concentration (r = -0.4; P = .03). Serotonin concentration also correlated with pain threshold (r = 0.4; P = .02) and stool threshold (r = 0.5; P = .06), which correlated inversely with defecation frequency (r = -0.3; P = .10). CONCLUSIONS: FC and IBS-C, based on Rome III criteria, are not distinct disorders, symptomatically or physiologically. Instead, they appear to lie in a spectrum of visceral sensitivity modulated by serotonin signaling. Symptom response to meal ingestion should be considered in patient classification.

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