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Irritable Bowel Syndrome: HELP
Articles from University of Bologna
Based on 51 articles published since 2008
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These are the 51 published articles about Irritable Bowel Syndrome that originated from University of Bologna during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Guideline Rome Foundation Working Team Report on Post-Infection Irritable Bowel Syndrome. 2019

Barbara, Giovanni / Grover, Madhusudan / Bercik, Premysl / Corsetti, Maura / Ghoshal, Uday C / Ohman, Lena / Rajilić-Stojanović, Mirjana. ·Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy. Electronic address: giovanni.barbara@unibo.it. · Enteric NeuroScience Program, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. · Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada. · Nottingham Digestive Diseases Biomedical Research Centre, National Institute for Health Research, Nottingham University Hospitals NHS Trust, University of Nottingham, UK. · Department of Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India. · Department of Microbiology and Immunology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. · Department of Biochemical Engineering and Biotechnology, Faculty of Technology and Metallurgy, University of Belgrade, Belgrade, Serbia. ·Gastroenterology · Pubmed #30009817.

ABSTRACT: BACKGROUND & AIMS: The existence of postinfection irritable bowel syndrome (PI-IBS) has been substantiated by epidemiology studies conducted in diverse geographic and clinical settings. However, the available evidence has not been well summarized, and there is little guidance for diagnosis and treatment of PI-IBS. The ROME Foundation has produced a working team report to summarize the available evidence on the pathophysiology of PI-IBS and provide guidance for diagnosis and treatment, based on findings reported in the literature and clinical experience. METHODS: The working team conducted an evidence-based review of publication databases for articles describing the clinical features (diagnosis), pathophysiology (intestinal sensorimotor function, microbiota, immune dysregulation, barrier dysfunction, enteroendocrine pathways, and genetics), and animal models of PI-IBS. We used a Delphi-based consensus system to create guidelines for management of PI-IBS and a developed treatment algorithm based on published findings and experiences of team members. RESULTS: PI-IBS develops in about 10% of patients with infectious enteritis. Risk factors include female sex, younger age, psychological distress during or before acute gastroenteritis, and severity of the acute episode. The pathogenesis of PI-PBS appears to involve changes in the intestinal microbiome as well as epithelial, serotonergic, and immune system factors. However, these mechanisms are incompletely understood. There are no evidence-based, effective pharmacologic strategies for treatment of PI-IBS. We provide a consensus-based treatment algorithm, based on clinical presentation and potential disease mechanisms. CONCLUSIONS: Based on a systematic review of the literature and team experience, we summarize the clinical features, pathophysiology (from animal models and human studies), and progression of PI-IBS. Based on these findings, we present an algorithm for diagnosis and treatment of PI-IBS based on team consensus. We also propose areas for future investigation.

2 Review New concepts on intestinal microbiota and the role of the non-absorbable antibiotics with special reference to rifaximin in digestive diseases. 2018

Bajaj, Jasmohan S / Barbara, Giovanni / DuPont, Herbert L / Mearin, F / Gasbarrini, Antonio / Tack, Jan. ·Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, USA. · Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy. · Center for Infectious Diseases, The University of Texas School of Public Health, Baylor College of Medicine, Kelsey Research Foundation, Houston, TX, USA. · Institute of Functional and Motor Digestive Disorders, Centro Médico Teknon, Barcelona, Spain. · Catholic University of Rome, Gemelli University Hospital, Rome, Italy. Electronic address: antonio.gasbarrini@unicatt.it. · Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Clinical and Experimental Medicine, University of Leuven, Belgium; Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium. ·Dig Liver Dis · Pubmed #29807873.

ABSTRACT: Digestive diseases are a broad range of chronic disorders that substantially and negatively impact the patients' quality of life. Here, we review our current understanding on the pathophysiology of hepatic encephalopathy, irritable bowel syndrome, and diverticular disease, with a special focus on the gut microbiota composition associated with these disorders. Furthermore, we review the current clinical practice for their therapeutic treatments, including probiotics, diet change, non-adsorbable disaccharides, and antibiotics. We highlight that broad-spectrum non-adsorbable antibiotics, such as rifaximin, are quite effective and safe for the treatment of all essayed digestive diseases.

3 Review Advancements in drug development for diarrhea-predominant irritable bowel syndrome. 2018

Dothel, Giovanni / Barbaro, Maria Raffaella / Raschi, Emanuel / Barbara, Giovanni / De Ponti, Fabrizio. ·a Department of Medical and Surgical Sciences , University of Bologna , Bologna , Italy. ·Expert Opin Investig Drugs · Pubmed #29451407.

ABSTRACT: INTRODUCTION: Diarrhea-predominant irritable bowel syndrome (IBS-D) is a common disorder characterized by a complex pathophysiology hampering optimal targeted drug development. Recent advances in our understanding of key underlying mechanisms prompted novel therapeutics including novel pharmacological approaches. AREAS COVERED: This review summarizes the latest advancements in the pipeline of IBS-D drugs focusing on new pharmacological targets, efficacy and safety of medicinal products considering the recent harmonization of regulatory requirements by the FDA and the EMA. EXPERT OPINION: The new 5-HT

4 Review Colonic immune cells in irritable bowel syndrome: A systematic review and meta-analysis. 2018

Bashashati, M / Moossavi, S / Cremon, C / Barbaro, M R / Moraveji, S / Talmon, G / Rezaei, N / Hughes, P A / Bian, Z X / Choi, C H / Lee, O Y / Coëffier, M / Chang, L / Ohman, L / Schmulson, M J / McCallum, R W / Simren, M / Sharkey, K A / Barbara, G. ·Division of Gastroenterology, Department of Internal Medicine, Texas Tech University Health Sciences Center/Paul L. Foster School of Medicine, El Paso, TX, USA. · Digestive Oncology Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran. · Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada. · Department of Medical and Surgical Sciences, Centre for Applied Biomedical Research, University of Bologna, Bologna, Italy. · Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA. · Fred and Pamela Buffet Cancer Center, Omaha, NE, USA. · Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran. · Centre for Nutritional and Gastrointestinal Diseases, Department of Medicine, University of Adelaide and South Australian Health Medical Health Research Institute, Adelaide, SA, Australia. · School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR, China. · Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea. · Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea. · Normandie Univ, INSERM unit 1073 "Nutrition, inflammation and brain-gut axis", Institute for Research and Innovation in Biomedicine, Rouen Medical University and Rouen University Hospital, Rouen, France. · G Oppenheimer Center of Neurobiology of Stress and Resilience, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. · Departments of Internal Medicine and Clinical Nutrition and Microbiology and Immunology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. · Laboratorio de Hígado, Páncreas y Motilidad (HIPAM), Unidad de Investigación en Medicina Experimental, Facultad de Medicina-Universidad Nacional Autónoma de México (UNAM), Hospital General de México, Mexico City, Mexico. · Department of Internal Medicine & Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. · Center for Functional GI and Motility Disorders, University of North Carolina, Chapel Hill, NC, USA. · Hotchkiss Brain Institute and Snyder Institute for Chronic Diseases, Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada. ·Neurogastroenterol Motil · Pubmed #28851005.

ABSTRACT: BACKGROUND & AIMS: Increases in mucosal immune cells have frequently been observed in irritable bowel syndrome (IBS) patients. However, this finding is not completely consistent between studies, possibly due to a combination of methodological variability, population differences and small sample sizes. We performed a meta-analysis of case-control studies that compared immune cell counts in colonic biopsies of IBS patients and controls. METHODS: PubMed and Embase were searched in February 2017. Results were pooled using standardized mean difference (SMD) and were considered significant when zero was not within the 95% confidence interval (CI). Heterogeneity was assessed based on I KEY RESULTS: Twenty-two studies on 706 IBS patients and 401 controls were included. Mast cells were increased in the rectosigmoid (SMD: 0.38 [95% CI: 0.06-0.71]; P = .02) and descending colon (SMD: 1.69 [95% CI: 0.65-2.73]; P = .001) of IBS patients. Increased mast cells were observed in both constipation (IBS-C) and diarrhea predominant IBS (IBS-D). CD3 CONCLUSIONS & INFERENCES: Mast cells and CD3

5 Review The Overlapping Area of Non-Celiac Gluten Sensitivity (NCGS) and Wheat-Sensitive Irritable Bowel Syndrome (IBS): An Update. 2017

Catassi, Carlo / Alaedini, Armin / Bojarski, Christian / Bonaz, Bruno / Bouma, Gerd / Carroccio, Antonio / Castillejo, Gemma / De Magistris, Laura / Dieterich, Walburga / Di Liberto, Diana / Elli, Luca / Fasano, Alessio / Hadjivassiliou, Marios / Kurien, Matthew / Lionetti, Elena / Mulder, Chris J / Rostami, Kamran / Sapone, Anna / Scherf, Katharina / Schuppan, Detlef / Trott, Nick / Volta, Umberto / Zevallos, Victor / Zopf, Yurdagül / Sanders, David S. ·Department of Pediatrics, Marche Polytechnic University, 60121 Ancona, Italy. c.catassi@univpm.it. · Department of Medicine, Columbia University Medical Center, New York, NY 10027, USA. aa819@cumc.columbia.edu. · Medical Department, Division of Gastroenterology, Infectiology and Rheumatology, Charité, Campus Benjamin Franklin, 12203 Berlin, Germany. christian.bojarski@charite.de. · Department of Gastroenterology and Liver Diseases, CHU, 38043 Grenoble, France. bbonaz@chu-grenoble.fr. · Celiac Center Amsterdam, Department of Gastroenterology, VU University Medical Center, 1117 Amsterdam, The Netherlands. g.bouma@vumc.nl. · Department of Internal Medicine, "Giovanni Paolo II" Hospital, Sciacca (AG) and University of Palermo, 92019 Sciacca, Italy. acarroccio@hotmail.com. · Paediatric Gastroenterology Unit, Sant Joan de Reus University Hospital. IISPV, 43003 Tarragona, Spain. gcv@tinet.cat. · Department of Internal and Experimental Medicine Magrassi-Lanzara, University of Campania Luigi Vanvitelli, 80131 Naples, Italy. laura.demagistris@unicampania.it. · Medical Clinic 1, Friedrich-Alexander-University Erlangen-Nürnberg, 91054 Erlangen, Germany. walburga.dieterich@uk-erlangen.de. · Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), University of Palermo, 90133 Palermo, Italy. diana.diliberto@unipa.it. · Center for the Prevention and Diagnosis of Celiac Disease, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy. lucelli@yahoo.com. · Center for Celiac Research and Treatment, Massachusetts General Hospital, Boston, MA 02114, USA. AFASANO@mgh.harvard.edu. · Academic Department of Neurosciences, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield S10 2JF, UK. Marios.Hadjivassiliou@sth.nhs.uk. · Academic Unit of Gastroenterology, Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, Sheffield S10 2TN, UK. matthew.kurien@sth.nhs.uk. · Department of Pediatrics, Marche Polytechnic University, 60121 Ancona, Italy. mariaelenalionetti@gmail.com. · Celiac Center Amsterdam, Department of Gastroenterology, VU University Medical Center, 1117 Amsterdam, The Netherlands. cjmulder@vumc.nl. · Gastroenterology Unit, Milton Keynes University Hospital, Milton Keynes MK6 5LD, UK. krostami@hotmail.com. · Center for Celiac Research and Treatment, Massachusetts General Hospital, Boston, MA 02114, USA. annasapone@yahoo.it. · German Research Centre for Food Chemistry, Leibniz Institute, Lise-Meitner-Straße 34, D-85354 Freising, Germany. Katharina.Scherf@lrz.tu-muenchen.de. · Institute of Translational Immunology, University Medical Center, Johannes Gutenberg University, 55131 Mainz, Germany. detlef.schuppan@unimedizin-mainz.de. · Academic Unit of Gastroenterology, Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, Sheffield S10 2TN, UK. nick.trott@sth.nhs.uk. · Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy. umberto.volta@aosp.bo.it. · Institute of Translational Immunology, University Medical Center, Johannes Gutenberg University, 55131 Mainz, Germany. zevallos@uni-mainz.de. · Medical Clinic 1, Friedrich-Alexander-University Erlangen-Nürnberg, 91054 Erlangen, Germany. Yurdaguel.Zopf@uk-erlangen.de. · Academic Unit of Gastroenterology, Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, Sheffield S10 2TN, UK. david.sanders@sth.nhs.uk. ·Nutrients · Pubmed #29160841.

ABSTRACT: Gluten-related disorders have recently been reclassified with an emerging scientific literature supporting the concept of non-celiac gluten sensitivity (NCGS). New research has specifically addressed prevalence, immune mechanisms, the recognition of non-immunoglobulin E (non-IgE) wheat allergy and overlap of NCGS with irritable bowel syndrome (IBS)-type symptoms. This review article will provide clinicians with an update that directly impacts on the management of a subgroup of their IBS patients whose symptoms are triggered by wheat ingestion.

6 Review Smoking in Irritable Bowel Syndrome: A Systematic Review. 2017

Sirri, Laura / Grandi, Silvana / Tossani, Eliana. ·a Laboratory of Psychosomatics and Clinimetrics, Department of Psychology , University of Bologna , Bologna , Italy. ·J Dual Diagn · Pubmed #28609199.

ABSTRACT: OBJECTIVE: The aim of this review was to examine (1) the prevalence of smoking in subjects with irritable bowel syndrome (IBS), (2) whether smoking prevalence significantly differs between subjects with and without IBS, and (3) whether smoking significantly predicts the presence or the development of IBS. METHODS: Articles were retrieved by systematically searching the Scopus, Web of Science, and PubMed electronic databases from inception to July 2016, using the keywords "smoking" and "tobacco" combined with "irritable bowel syndrome." Reference lists of included articles were also searched. Articles were included if they (1) reported data on smoking prevalence in subjects with IBS and/or on the association (assessed by means of multivariate analyses) between smoking and IBS, (2) identified IBS according to Manning criteria or Rome I-III criteria, (3) were English-language articles, and (4) involved only adult subjects. RESULTS: The electronic searches yielded a total of 1,637 records, and 42 articles met inclusion criteria. Another 13 articles were retrieved through manual search, leading to a total of 55 included articles. Smoking prevalence in subjects with IBS was assessed by 48 articles and ranged from 0% in university students to 47.1% in patients with microscopic colitis. Thirty-three articles compared smoking prevalence between subjects with and without IBS. In 25 articles no significant difference was found. In seven articles smoking was significantly more frequent in subjects with IBS compared to those without IBS, while one study found a significantly higher smoking prevalence in controls. Eighteen multivariate analyses assessing the association between smoking and IBS were presented in 16 articles. Only one study employed a prospective design. In 11 analyses, smoking was not significantly associated with IBS after adjusting for covariates. In seven studies smoking independently predicted the presence of IBS. CONCLUSIONS: According to the selected articles, a significant association between smoking and IBS cannot be confirmed. However, different shortcomings may hinder generalizability and comparability of many studies. A dimensional assessment of smoking, a prospective design, the differentiation between IBS subgroups, and the recruitment of patients in clinical settings, especially in primary care, are necessary to clarify the role of smoking in IBS.

7 Review Diagnostic challenges of symptomatic uncomplicated diverticular disease. 2017

Cremon, Cesare / Bellacosa, Lara / Barbaro, Maria R / Cogliandro, Rosanna F / Stanghellini, Vincenzo / Barbara, Giovanni. ·Department of Medical and Surgical Sciences, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy. · Department of Medical and Surgical Sciences, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy - giovanni.barbara@unibo.it. ·Minerva Gastroenterol Dietol · Pubmed #28079347.

ABSTRACT: Colonic diverticulosis is a common condition in Western industrialized countries occurring in up to 65% of people over the age of 60 years. Only a minority of these subjects (about 10-25%) experience symptoms, fulfilling Rome III Diagnostic Criteria for irritable bowel syndrome (IBS) diagnosis (IBS-like symptoms) in 10% to 66% of cases. Symptomatic uncomplicated diverticular disease (SUDD) is a syndrome characterized by recurrent abdominal symptoms attributed to diverticula in the absence of macroscopically evident alterations other than the presence of diverticula. Due to the different peak of incidence, the overlap between SUDD and IBS is predominantly present in middle-aged or older patients. In these cases, it is very complex to establish if the symptoms are related to the presence of diverticula or due to an overlapping IBS. In fact, the link between gastrointestinal symptoms and diverticula is unclear, and the mechanism by which diverticula may induce the development of IBS-like symptoms remains to be elucidated. Currently, the etiology and pathophysiology of SUDD, particularly when IBS-like symptoms are present, are not completely understood, and thus these two entities remain a diagnostic challenge not only for the general practitioner but also for the gastroenterologist. Although many issues remain open and unresolved, some minimize the importance of a distinction of these two entities as dietary and pharmacological management may be largely overlapping.

8 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.

9 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.

10 Review Sensitivity to wheat, gluten and FODMAPs in IBS: facts or fiction? 2016

De Giorgio, Roberto / Volta, Umberto / Gibson, Peter R. ·Department of Medical and Surgical Sciences, Centro di Ricerca Bio-Medica Applicata (C.R.B.A.) and Digestive System, St. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy. · Department of Gastroenterology Alfred Hospital, Monash University, Melbourne, Australia. ·Gut · Pubmed #26078292.

ABSTRACT: IBS is one of the most common types of functional bowel disorder. Increasing attention has been paid to the causative role of food in IBS. Food ingestion precipitates or exacerbates symptoms, such as abdominal pain and bloating in patients with IBS through different hypothesised mechanisms including immune and mast cell activation, mechanoreceptor stimulation and chemosensory activation. Wheat is regarded as one of the most relevant IBS triggers, although which component(s) of this cereal is/are involved remain(s) unknown. Gluten, other wheat proteins, for example, amylase-trypsin inhibitors, and fructans (the latter belonging to fermentable oligo-di-mono-saccharides and polyols (FODMAPs)), have been identified as possible factors for symptom generation/exacerbation. This uncertainty on the true culprit(s) opened a scenario of semantic definitions favoured by the discordant results of double-blind placebo-controlled trials, which have generated various terms ranging from non-coeliac gluten sensitivity to the broader one of non-coeliac wheat or wheat protein sensitivity or, even, FODMAP sensitivity. The role of FODMAPs in eliciting the clinical picture of IBS goes further since these short-chain carbohydrates are found in many other dietary components, including vegetables and fruits. In this review, we assessed current literature in order to unravel whether gluten/wheat/FODMAP sensitivity represent 'facts' and not 'fiction' in IBS symptoms. This knowledge is expected to promote standardisation in dietary strategies (gluten/wheat-free and low FODMAP) as effective measures for the management of IBS symptoms.

11 Review Inflammatory bowel disease and irritable bowel syndrome: similarities and differences. 2014

Barbara, Giovanni / Cremon, Cesare / Stanghellini, Vincenzo. ·Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy. ·Curr Opin Gastroenterol · Pubmed #24811054.

ABSTRACT: PURPOSE OF REVIEW: Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are classically viewed as dichotomous conditions. The former is perceived as a typical organic disease, and the latter is regarded as a disorder of gut function driven by mood. Recent research identified some shared contributing factors, which will be discussed here. RECENT FINDINGS: Mounting evidence shows the importance in both IBD and IBS of genetic, microbiological, epithelial, and immunological factors. In some instances, these factors overlap in the two conditions as shown by: involvement of brain-gut axis dysfunction in IBD, implication of TNFSF gene in Crohn's disease and IBS, evidence of abnormal microbiota and its impact on host functions, identification of low-grade inflammation in subsets of IBS patients, and development of IBS symptoms in patients with IBD in remission. SUMMARY: IBD and IBS remain separate conditions although there are some overlapping mechanisms. Both research and clinical management would benefit from considering a functional approach for certain manifestations of IBD and accepting an organic view in subsets of IBS patients.

12 Review Lubiprostone: pharmacokinetic, pharmacodynamic, safety and regulatory aspects in the treatment of constipation-predominant irritable bowel syndrome. 2014

Raschi, Emanuel / De Ponti, Fabrizio. ·University of Bologna, Department of Medical and Surgical Sciences, Pharmacology Unit, Alma Mater Studiorum , Via Irnerio, 48, I-40126 Bologna BO , Italy. ·Expert Opin Drug Metab Toxicol · Pubmed #24387275.

ABSTRACT: INTRODUCTION: Lubiprostone acts locally (apical membrane of human intestinal epithelial cells) as a highly selective type-2 chloride channel activator. It was approved in the USA for chronic idiopathic constipation (January 2006) and in women aged ≥ 18 years suffering from irritable bowel syndrome with constipation (IBS-C) (April 2008). So far, the only other pro-secretory medication approved in IBS-C and currently available in USA and Europe (since August and November 2012, respectively) is linaclotide. AREAS COVERED: This review outlines the regulatory history, pharmacokinetic, pharmacodynamic and safety data in the treatment of IBS-C with a European perspective. It is based on publicly available data, namely, published literature, drug labels and the FDA's spontaneous reporting system. EXPERT OPINION: Although interesting pharmacodynamic data suggest that lubiprostone may have additional mechanisms of action, its beneficial effects in IBS-C must be confirmed in the actual clinical scenario taking into account the new version of European Medicines Agency's guideline. This is especially important with regard to duration of studies (recommended to be at least 6 months) to adequately assess long-term sustained efficacy, withdrawal, rebound and safety. Further research is warranted in uncertain areas (i.e., males, pediatric and elderly patients). On the basis of current data, it is still too early to draw definite conclusions on the overall risk-benefit balance for IBS-C.

13 Review Perspectives on irritable bowel syndrome: where have we been? Where are we now? 2013

Stanghellini, Vincenzo. ·Department of Digestive Diseases and Internal Medicine, University of Bologna, St Orsola-Malpighi Hospital, Via Massarenti 9, 40138 Bologna, Italy. v.stanghellini@unibo.it ·Expert Rev Gastroenterol Hepatol · Pubmed #23859754.

ABSTRACT: Irritable bowel syndrome is a chronic functional disorder with a complex etiology and multiple overlapping symptoms. Irritable bowel syndrome is characterized by long-lasting abdominal pain or discomfort, abnormal bowel habits and typically inadequate response to many of the available therapies.

14 Review Mechanisms underlying visceral hypersensitivity in irritable bowel syndrome. 2011

Barbara, Giovanni / Cremon, Cesare / De Giorgio, Roberto / Dothel, Giovanni / Zecchi, Lisa / Bellacosa, Lara / Carini, Giovanni / Stanghellini, Vincenzo / Corinaldesi, Roberto. ·Department of Clinical Medicine and Center for Applied Biomedical Research, University of Bologna, Bologna, Italy. giovanni.barbara@unibo.it ·Curr Gastroenterol Rep · Pubmed #21537962.

ABSTRACT: Visceral hypersensitivity is currently considered a key pathophysiological mechanism involved in pain perception in large subgroups of patients with functional gastrointestinal disorders, including irritable bowel syndrome (IBS). In IBS, visceral hypersensitivity has been described in 20%-90% of patients. The contribution of the central nervous system and psychological factors to visceral hypersensitivity in patients with IBS may be significant, although still debated. Peripheral factors have gained increasing attention following the recognition that infectious enteritis may trigger the development of persistent IBS symptoms, and the identification of mucosal immune, neural, endocrine, microbiological, and intestinal permeability abnormalities. Growing evidence suggests that these factors play an important role in pain transmission from the periphery to the brain via sensory nerve pathways in large subsets of patients with IBS. In this review, we will report on recent data on mechanisms involved in visceral hypersensitivity in IBS, with particular attention paid to peripheral mechanisms.

15 Review [Post-infectious irritable bowel syndrome]. 2011

Pallotti, F / Fogacci, E / Frisoni, C / Serra, M / Bellacosa, L / Carini, G / Cremon, C / De Giorgio, R / Stanghellini, V / Corinaldesi, R / Barbara, G. ·Dipartimento di Medicina Clinica, Università di Bologna, Italy. ·Clin Ter · Pubmed #21533323.

ABSTRACT: Acute infectious gastroenteritis is the strongest known risk factor for the development of irritable bowel syndrome (IBS), one of the most common functional gastrointestinal disorders. The knowledge about the incidence and prevalence of post-infectious IBS (PI-IBS) in the general population is still limited. Risk factors have been identified in the development of PI-IBS. These include the virulence of the pathogen, younger age, female sex, the long duration of the initial illness and the presence of psychological disturbances. Histopathologic data demonstrate a low-grade mucosal inflammation in a subset of patients with IBS. Furthermore, a change in intestinal microflora could also be involved although confirmatory studies are required. The use of probiotics or non absorbable antibiotics during the acute infective episode could play a preventive role. Nonetheless, the discovery that an infective episode may trigger the development of IBS has not substantially changed the clinical management of this subset of patients compared to the classical (non infective) form of IBS. Future studies aimed at identifying specific therapies are waited.

16 Review Aminosalicylates and other anti-inflammatory compounds for irritable bowel syndrome. 2009

Barbara, Giovanni / Stanghellini, Vincenzo / Cremon, Cesare / De Giorgio, Roberto / Fronzoni, Lucia / Serra, Mauro / Corinaldesi, Roberto. ·Department of Clinical Medicine and Center for Applied Biomedical Research, University of Bologna, Bologna, Italy. giovanni.barbara@unibo.it ·Dig Dis · Pubmed #20203507.

ABSTRACT: Growing evidence suggests that gastrointestinal immune activation may affect intestinal function and sensory perception, which contribute to symptom generation in patients with irritable bowel syndrome (IBS). The identification of higher counts of immunocytes (e.g. T cells and mast cells), mucosal and systemic immune activation, and increased mucosal permeability in patients with IBS has stimulated interest in the potential development of therapeutic approaches aimed at targeting the immune system and inflammation. Although an initial attempt in a pilot trial with steroids in patients with post-infective IBS failed, there has been renewed interest for mast cell stabilizers and the therapeutic potential of aminosalicylates. A recent randomized, double-blind, placebo-controlled pilot trial assessed the effect of mesalazine on intestinal immune cells and symptom perception in patients with IBS. Mesalazine markedly reduced mucosal immune cells and mast cells in particular, compared to placebo. In addition, mesalazine significantly improved general well-being. Mesalazine may enhance epithelial barrier function, and preliminary data suggest that it may alter faecal bacterial profiles in IBS patients. Nevertheless, the exact mechanism through which this drug affects immune activation in the intestine of patients with IBS remains unknown. There is a need for further studies to prove the efficacy of mesalazine for IBS. Further studies aimed at assessing the role of aminosalicylates and other approaches with potential anti-inflammatory activity, including probiotics, non-absorbable antibiotics, histamine receptor antagonists and protease inhibitors on IBS symptoms or pathophysiology are now warranted.

17 Review Biomarkers in IBS: when will they replace symptoms for diagnosis and management? 2009

Barbara, Giovanni / Stanghellini, Vincenzo. ·Department of Clinical Medicine, S. Orsola-Malpighi Hospital, Via Massarenti, 9, I-40138 - Bologna, Italy. ·Gut · Pubmed #19923339.

ABSTRACT: -- No abstract --

18 Review Postinfectious irritable bowel syndrome. 2009

Barbara, Giovanni / Cremon, Cesare / Pallotti, Francesca / De Giorgio, Roberto / Stanghellini, Vincenzo / Corinaldesi, Roberto. ·Department of Internal Medicine and Gastroenterology and CRBA, University of Bologna, Bologna, Italy. giovanni.barbara@unibo.it ·J Pediatr Gastroenterol Nutr · Pubmed #19300138.

ABSTRACT: Irritable bowel syndrome (IBS) is a gastrointestinal disorder characterized by abdominal pain and changes in bowel habits, not sustained by structural changes. There is now consistent evidence indicating that IBS may be the adverse outcome of an acute episode of infectious gastroenteritis, the so-called postinfectious (PI) IBS. The infectious agents involved in the development of PI-IBS include pathogenic bacteria, parasites, and viruses. Abdominal pain and diarrhea are the most common symptoms of PI-IBS. Several studies identified a number of risk factors increasing the susceptibility for PI-IBS development. These include the virulence of the pathogen, the severity, and duration of the acute enteritis, younger age, female sex, and psychological disturbances. Several mucosal abnormalities in the colon or ileum of patients who develop PI-IBS have been described. These changes include increased mucosal permeability, an increased amount of intraepithelial lymphocytes, lamina propria T cells, and mast cells, as well as serotonin-containing enteroendocrine cells. The mediators released by these activated cells may evoke enteric nervous system responses, excite sensory afferent pathways, and induce visceral hyperalgesia. Little is known about the prognosis of PI-IBS, although it is likely better than that of nonspecific IBS. There is little evidence about a specific treatment for PI-IBS. Although probiotics and antibiotics may be promising in the prevention of PI-IBS, the efficacy of these treatments should be assessed in an ad hoc designed study.

19 Review Probiotics and irritable bowel syndrome: rationale and clinical evidence for their use. 2008

Barbara, Giovanni / Stanghellini, Vincenzo / Cremon, Cesare / De Giorgio, Roberto / Gargano, Luciana / Cogliandro, Rosanna / Pallotti, Francesca / Corinaldesi, Roberto. ·Department of Internal Medicine and Gastroenterology, University of Bologna, Bologna, Italy. giovanni.barbara@unibo.it ·J Clin Gastroenterol · Pubmed #18685517.

ABSTRACT: Growing evidence suggests a potential role of intestinal microbiota in irritable bowel syndrome (IBS) pathophysiology and symptom generation. Earlier studies based on classic microbiologic techniques hypothesized the presence of qualitative changes in intestinal microbiota in IBS patients. Recently, studies with molecular techniques have provided evidence of significant changes in microbial profiles in IBS and that the composition may be correlated with certain symptoms reported by patients. Although these studies are far from being exhaustive and conclusive they provide promising results that deserve further investigation. In addition, initial evidence indicated the presence of increased amounts of bacteria in the upper small intestine of IBS patients, a condition know as small intestinal bacterial overgrowth. However, the results of these studies have provided contradictory results suggesting that this area requires further work. These qualitative and quantitative changes in intestinal microbiota may induce different effects on the intestinal mucosa including mucosal barrier defects and immune activation which may contribute to symptom generation. Studies in IBS patients have attempted to target changes in intestinal microflora with different therapeutic approaches, such as the use of prebiotics, probiotics, synbiotics, and nonabsorbable and systemic antibiotics. Overall, the results obtained in probiotic clinical trials suggest some beneficial effect over placebo in the relief of IBS symptoms. However, these results, although encouraging, should be confirmed in larger well-designed, placebo-controlled studies. A number of open questions remain to be addressed, including the dose, type, and time of administration of probiotics.

20 Review Is irritable bowel syndrome an inflammatory disorder? 2008

De Giorgio, Roberto / Barbara, Giovanni. ·Department of Internal Medicine and Gastroenterology, Building #5 (Nuove Patologie), St. Orsola-Malpighi Hospital, Via Massarenti, 9, I-40138 Bologna, Italy. deg@aosp.bo.it ·Curr Gastroenterol Rep · Pubmed #18627650.

ABSTRACT: Histopathologic data demonstrate low-grade mucosal inflammation in a subset of patients with irritable bowel syndrome (IBS). This inflammatory infiltrate is mainly represented by increased numbers of T lymphocytes and mast cells lying in the lamina propria. The close apposition of immunocytes to gut nerves supplying the mucosa provides a basis for neuroimmune cross-talk, which may explain gut sensorimotor dysfunction and related symptoms in patients with IBS. A previous gastroenteritis (due to Campylobacter jejuni, Salmonella, Shigella, Escherichia coli, and, likely, viruses) is now an established etiologic factor for IBS (hence, postinfectious IBS). Other putative causes, such as undiagnosed food allergies, genetic abnormalities, stress, or bile acid malabsorption, may also promote and maintain a low-grade mucosal inflammation in IBS. The identification of mucosal inflammation in IBS has pathophysiologic implications and paves the way for novel therapeutic options.

21 Clinical Trial Dietary geraniol ameliorates intestinal dysbiosis and relieves symptoms in irritable bowel syndrome patients: a pilot study. 2018

Rizzello, Fernando / Ricci, Chiara / Scandella, Michela / Cavazza, Elena / Giovanardi, Elisabetta / Valerii, Maria Chiara / Campieri, Massimo / Comparone, Antonietta / De Fazio, Luigia / Candela, Marco / Turroni, Silvia / Spisni, Enzo. ·Department of Medical and Surgical Sciences, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy. · Department of Clinical and Experimental Sciences, University of Brescia, Spedali Civili 1, 25121, Brescia, Italy. · Department of Biological, Geological and Environmental Sciences, Biology Unit, University of Bologna, Via Selmi 3, 40126, Bologna, Italy. · Department of Pharmacy and Biotechnology, University of Bologna, Via Belmeloro 6, 40126, Bologna, Italy. · Department of Biological, Geological and Environmental Sciences, Biology Unit, University of Bologna, Via Selmi 3, 40126, Bologna, Italy. enzo.spisni@unibo.it. ·BMC Complement Altern Med · Pubmed #30567535.

ABSTRACT: BACKGROUND: (Trans)-3,7-Dimethyl-2,6-octadien-1-ol, commonly called geraniol (Ge-OH), is an acyclic monoterpene alcohol with well-known anti-inflammatory and antimicrobial properties. Ge-OH is a non-toxic compound classified as Generally Recognized As Safe (GRAS) by the US Food and Drug Administration and the European Food Security Agency. METHODS: Ge-OH was orally administered at a maximum daily dose of 8 mg kg RESULTS: The results show that orally administered Ge-OH is a powerful modulator of the intestinal microbial ecosystem, capable of leading to increased relative abundances of Collinsella and especially Faecalibacterium, a well-known health-promoting butyrate producer consistently found to be decreased in IBS patients. Moreover, Ge-OH strongly improved the clinical symptoms of colitis by significantly reducing the score recorded by the VAS-IBS questionnaire. Clinical improvement was associated with a significant reduction in the circulating MIP-1β, a chemokine found to be increased in several IBS patients. CONCLUSION: Ge-OH could be a powerful component for food supplement targeted to the treatment of IBS patients. TRIAL REGISTRATION: ISRCTN47041881 , retrospectively registered on 19th July 2018.

22 Clinical Trial Randomised clinical trial: the analgesic properties of dietary supplementation with palmitoylethanolamide and polydatin in irritable bowel syndrome. 2017

Cremon, C / Stanghellini, V / Barbaro, M R / Cogliandro, R F / Bellacosa, L / Santos, J / Vicario, M / Pigrau, M / Alonso Cotoner, C / Lobo, B / Azpiroz, F / Bruley des Varannes, S / Neunlist, M / DeFilippis, D / Iuvone, T / Petrosino, S / Di Marzo, V / Barbara, G. ·Department of Medical and Surgical Sciences, Centre for Applied Biomedical Research, University of Bologna, Bologna, Italy. · Digestive System Research Unit, Departments of Gastroenterology, Institut de Recerca Vall d'Hebron Hospital Universitari Vall d'Hebron Universitat Autònoma de Barcelona (Departamento de Medicina) Barcelona and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain. · Institut des Maladies de l'Appareil Digestif, Hotel Dieu, Nantes, France. · Department of Pharmacy, University of Naples "Federico II", Naples, Italy. · Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli, Italy. · Epitech Group SpA, Saccolongo, Italy. ·Aliment Pharmacol Ther · Pubmed #28164346.

ABSTRACT: BACKGROUND: Intestinal immune activation is involved in irritable bowel syndrome (IBS) pathophysiology. While most dietary approaches in IBS involve food avoidance, there are fewer indications on food supplementation. Palmithoylethanolamide, structurally related to the endocannabinoid anandamide, and polydatin are dietary compounds which act synergistically to reduce mast cell activation. AIM: To assess the effect on mast cell count and the efficacy of palmithoylethanolamide/polydatin in patients with IBS. METHODS: We conducted a pilot, 12-week, randomised, double-blind, placebo-controlled, multicentre study assessing the effect of palmithoylethanolamide/polydatin 200 mg/20 mg or placebo b.d. on low-grade immune activation, endocannabinoid system and symptoms in IBS patients. Biopsy samples, obtained at screening visit and at the end of the study, were analysed by immunohistochemistry, enzyme-linked immunoassay, liquid chromatography and Western blot. RESULTS: A total of 54 patients with IBS and 12 healthy controls were enrolled from five European centres. Compared with controls, IBS patients showed higher mucosal mast cell counts (3.2 ± 1.3 vs. 5.3 ± 2.7%, P = 0.013), reduced fatty acid amide oleoylethanolamide (12.7 ± 9.8 vs. 45.8 ± 55.6 pmol/mg, P = 0.002) and increased expression of cannabinoid receptor 2 (0.7 ± 0.1 vs. 1.0 ± 0.8, P = 0.012). The treatment did not significantly modify IBS biological profile, including mast cell count. Compared with placebo, palmithoylethanolamide/polydatin markedly improved abdominal pain severity (P < 0.05). CONCLUSIONS: The marked effect of the dietary supplement palmithoylethanolamide/polydatin on abdominal pain in patients with IBS suggests that this is a promising natural approach for pain management in this condition. Further studies are now required to elucidate the mechanism of action of palmithoylethanolamide/polydatin in IBS. ClinicalTrials.gov number, NCT01370720.

23 Clinical Trial Randomised controlled trial of mesalazine in IBS. 2016

Barbara, Giovanni / Cremon, Cesare / Annese, Vito / Basilisco, Guido / Bazzoli, Franco / Bellini, Massimo / Benedetti, Antonio / Benini, Luigi / Bossa, Fabrizio / Buldrini, Paola / Cicala, Michele / Cuomo, Rosario / Germanà, Bastianello / Molteni, Paola / Neri, Matteo / Rodi, Marcello / Saggioro, Alfredo / Scribano, Maria Lia / Vecchi, Maurizio / Zoli, Giorgio / Corinaldesi, Roberto / Stanghellini, Vincenzo. ·Department of Medical and Surgical Sciences, Centre for Applied Biomedical Research, University of Bologna, Bologna, Italy. · Division of Gastroenterology SOD2, University Hospital Careggi, Florence, Italy. · Gastroenterology Unit, Ospedale Maggiore, Policlinico, Milan, Italy. · Gastroenterology Unit, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy. · Gastroenterology Unit, Department of Gastroenterology, University of Pisa, Pisa, Italy. · Department of Gastroenterology and Hepatology, Università Politecnica delle Marche, Ancona, Italy. · Gastroenterology Unit, University of Verona, Verona, Italy. · Division of Gastroenterology, Casa Sollievo Sofferenza Hospital, IRCCS, San Giovanni Rotondo, Italy. · Gastroenterology Unit of Comacchio/Lagosanto, Ferrara, Italy. · Gastroenterology Unit, University Campus Bio-Medico of Rome, Rome, Italy. · Digestive Motility Diseases, Department of Clinical Medicine and Surgery, Federico II University Hospital, Naples, Italy. · Gastroenterology Unit, S. Martino Hospital, Belluno, Italy. · Gastroenterology Unit, Department of Clinical Science, "L. Sacco" University Hospital, Milan, Italy. · Department of Medicine and Aging Sciences and CESI, G. D'Annunzio University and Foundation, Chieti, Italy. · Gastroenterology Unit, St. Andrea Hospital, Vercelli, Italy. · Department of Digestive Diseases, Hepatology and Clinical Nutrition, Dell'Angelo Hospital, Venice, Italy. · Division of Gastroenterology, AO San Camillo Forlanini, Rome, Italy. · Gastroenterology and Digestive Endoscopy Unit, IRCCS Policlinico San Donato, San Donato Milanese, Italy. · Santissima Annunziata Hospital, Cento, Italy. ·Gut · Pubmed #25533646.

ABSTRACT: OBJECTIVE: Low-grade intestinal inflammation plays a role in the pathophysiology of IBS. In this trial, we aimed at evaluating the efficacy and safety of mesalazine in patients with IBS. DESIGN: We conducted a phase 3, multicentre, tertiary setting, randomised, double-blind, placebo-controlled trial in patients with Rome III confirmed IBS. Patients were randomly assigned to either mesalazine, 800 mg, or placebo, three times daily for 12 weeks, and were followed for additional 12 weeks. The primary efficacy endpoint was satisfactory relief of abdominal pain/discomfort for at least half of the weeks of the treatment period. The key secondary endpoint was satisfactory relief of overall IBS symptoms. Supportive analyses were also performed classifying as responders patients with a percentage of affirmative answers of at least 75% or >75% of time. RESULTS: A total of 185 patients with IBS were enrolled from 21 centres. For the primary endpoint, the responder patients were 68.6% in the mesalazine group versus 67.4% in the placebo group (p=0.870; 95% CI -12.8 to 15.1). In explorative analyses, with the 75% rule or >75% rule, the percentage of responders was greater in the mesalazine group with a difference over placebo of 11.6% (p=0.115; 95% CI -2.7% to 26.0%) and 5.9% (p=0.404; 95% CI -7.8% to 19.4%), respectively, although these differences were not significant. For the key secondary endpoint, overall symptoms improved in the mesalazine group and reached a significant difference of 15.1% versus placebo (p=0.032; 95% CI 1.5% to 28.7%) with the >75% rule. CONCLUSIONS: Mesalazine treatment was not superior than placebo on the study primary endpoint. However, a subgroup of patients with IBS showed a sustained therapy response and benefits from a mesalazine therapy. TRIAL REGISTRATION NUMBER: ClincialTrials.gov number, NCT00626288.

24 Article Female-Specific Association Between Variants on Chromosome 9 and Self-Reported Diagnosis of Irritable Bowel Syndrome. 2018

Bonfiglio, Ferdinando / Zheng, Tenghao / Garcia-Etxebarria, Koldo / Hadizadeh, Fatemeh / Bujanda, Luis / Bresso, Francesca / Agreus, Lars / Andreasson, Anna / Dlugosz, Aldona / Lindberg, Greger / Schmidt, Peter T / Karling, Pontus / Ohlsson, Bodil / Simren, Magnus / Walter, Susanna / Nardone, Gerardo / Cuomo, Rosario / Usai-Satta, Paolo / Galeazzi, Francesca / Neri, Matteo / Portincasa, Piero / Bellini, Massimo / Barbara, Giovanni / Latiano, Anna / Hübenthal, Matthias / Thijs, Vincent / Netea, Mihai G / Jonkers, Daisy / Chang, Lin / Mayer, Emeran A / Wouters, Mira M / Boeckxstaens, Guy / Camilleri, Michael / Franke, Andre / Zhernakova, Alexandra / D'Amato, Mauro. ·Unit of Gastrointestinal Genetics, Department of Gastrointestinal and Liver Diseases, Biodonostia Health Research Institute, San Sebastián, Spain; Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden. · Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden. · Unit of Gastrointestinal Genetics, Department of Gastrointestinal and Liver Diseases, Biodonostia Health Research Institute, San Sebastián, Spain; Unit of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden. · Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden. · Unit of Gastrointestinal Genetics, Department of Gastrointestinal and Liver Diseases, Biodonostia Health Research Institute, San Sebastián, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Universidad del País Vasco, San Sebastián, Spain. · Gastoenterology Unit, Tema inflammation and infection, Karolinska University Hospital, Stockholm, Sweden. · Division for Family Medicine and Primary Care, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden. · Division for Family Medicine and Primary Care, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Stress Research Institute, Stockholm University, Stockholm, Sweden. · Department of Medicine Solna, Karolinska Institutet, Center for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden. · Division of Medicine, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden. · Lund University, Skåne University Hospital, Department of Internal Medicine, Lund, Sweden. · Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. · Division of Neuro and Inflammation Science, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden. · Gastroenterology Unit, Department of Clinical Medicine and Surgery, University Federico II, Naples, Italy. · Digestive Motility Diseases, Department of Clinical Medicine and Surgery, Federico II University Hospital, Naples, Italy. · SC Gastroenterologia, Azienda Ospedaliera G. Brotzu, Cagliari, Italy. · UOC Gastroenterologia, Padova University Hospital, Padova, Italy. · Department of Medicine and Aging Sciences and Center for Excellence on Aging, G. D'Annunzio University and Foundation, Chieti, Italy. · Department of Biomedical Sciences and Human Oncology, Clinica Medica A. Murri, University of Bari Medical School, Bari, Italy. · Gastroenterology Unit, Department of Gastroenterology, University of Pisa, Pisa, Italy. · Department of Medical and Surgical Sciences, University of Bologna, St. Orsola, Malpighi Hospital, Bologna, Italy. · Division of Gastroenterology, Istituto di Ricovero e Cura a Carattere Scientifico, Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy. · Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany. · Florey Institute of Neuroscience and Mental Health, Heidelberg, Victoria, Australia. · Department of Internal Medicine and Radboud Center of Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands; Department for Genomics and Immunoregulation, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany. · Department of Internal Medicine, Nutrition and Toxicology Research Institute Maastricht, School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, The Netherlands. · G. Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, California. · Translational Research Center for Gastro Intestinal Disorders, Katholieke Universiteit Leuven, Leuven, Belgium. · Clinical Enteric Neuroscience Translational and Epidemiological Research, and Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota. · Department of Genetics, University Medical Center Groningen, Groningen, The Netherlands. · Unit of Gastrointestinal Genetics, Department of Gastrointestinal and Liver Diseases, Biodonostia Health Research Institute, San Sebastián, Spain; Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden; Unit of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Ikerbasque, Basque Science Foundation, Bilbao, Spain. Electronic address: mauro.damato@ki.se. ·Gastroenterology · Pubmed #29626450.

ABSTRACT: BACKGROUND & AIMS: Genetic factors are believed to affect risk for irritable bowel syndrome (IBS), but there have been no sufficiently powered and adequately sized studies. To identify DNA variants associated with IBS risk, we performed a genome-wide association study (GWAS) of the large UK Biobank population-based cohort, which includes genotype and health data from 500,000 participants. METHODS: We studied 7,287,191 high-quality single nucleotide polymorphisms in individuals who self-reported a doctor's diagnosis of IBS (cases; n = 9576) compared to the remainder of the cohort (controls; n = 336,499) (mean age of study subjects, 40-69 years). Genome-wide significant findings were further investigated in 2045 patients with IBS from tertiary centers and 7955 population controls from Europe and the United States, and a small general population sample from Sweden (n = 249). Functional annotation of GWAS results was carried out by integrating data from multiple biorepositories to obtain biological insights from the observed associations. RESULTS: We identified a genome-wide significant association on chromosome 9q31.2 (single nucleotide polymorphism rs10512344; P = 3.57 × 10 CONCLUSIONS: In a sufficiently powered GWAS of IBS, we associated variants at the locus 9q31.2 with risk of IBS in women. This observation may provide additional rationale for investigating the role of sex hormones and autonomic dysfunction in IBS.

25 Article Protease-activated receptor 1 is implicated in irritable bowel syndrome mediators-induced signaling to thoracic human sensory neurons. 2018

Desormeaux, Cleo / Bautzova, Tereza / Garcia-Caraballo, Sonia / Rolland, Corinne / Barbaro, Maria Raffaella / Brierley, Stuart M / Barbara, Giovanni / Vergnolle, Nathalie / Cenac, Nicolas. ·IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, Toulouse, France. · Visceral Pain Group, Human Physiology, Flinders University, Bedford Park, South Australia, Australia. · Centre for Nutrition and Gastrointestinal Diseases, Discipline of Medicine, University of Adelaide, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, South Australia, Australia. · Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy. · Department of Physiology and Pharmacology, Faculty of Medicine, University of Calgary, Calgary, Canada. ·Pain · Pubmed #29554016.

ABSTRACT: Proteases and protease-activated receptors (PARs) are major mediators involved in irritable bowel syndrome (IBS). Our objectives were to decipher the expression and functionality (calcium signaling) of PARs in human dorsal root ganglia (DRG) neurons and to define mechanisms involved in human sensory neuron signaling by IBS patient mediators. Human thoracic DRG were obtained from the national disease resource interchange. Expression of PAR1, PAR2, and PAR4 was assessed by immunohistochemistry and quantitative reverse transcription PCR (RT-qPCR) in whole DRG or in primary cultures of isolated neurons. Calcium signaling in response to PAR agonist peptides (PAR-AP), their inactive peptides (PAR-IP), thrombin (10 U/mL), supernatants from colonic biopsies of patients with IBS, or healthy controls, with or without PAR1 or PAR4 antagonist were studied in cultured human DRG neurons. PAR1, PAR2, and PAR4 were all expressed in human DRG, respectively, in 20%, 40%, and 40% of the sensory neurons. PAR1-AP increased intracellular calcium concentration in a dose-dependent manner. This increase was inhibited by PAR1 antagonism. By contrast, PAR2-AP, PAR4-AP, and PAR-IP did not cause calcium mobilization. PAR1-AP-induced calcium flux was significantly reduced by preincubation with PAR4-AP, but not with PAR2-AP. Thrombin increased calcium flux, which was inhibited by a PAR1 antagonist and increased by a PAR4 antagonist. Supernatants from colonic biopsies of patients with IBS induced calcium flux in human sensory neurons compared with healthy controls, and this induction was reversed by a PAR1 antagonist. Taken together, our results highlight that PAR1 antagonism should be investigated as a new therapeutic target for IBS symptoms.

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