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Identifying pathophysiology in functional bowel disorders: impact and consequences of Joint Hypermobility Syndrome, nutrition and microbiome.

Applicant Fried Michael
Number 166670
Funding scheme Project funding (Div. I-III)
Research institution Klinik für Gastroenterologie Universitätsspital Zürich
Institution of higher education University of Zurich - ZH
Main discipline Internal Medicine
Start/End 01.08.2016 - 31.01.2020
Approved amount 257'554.00
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All Disciplines (3)

Discipline
Internal Medicine
Clinical Pathophysiology
Clinical Nutritional Research

Keywords (6)

irritable bowel syndrome; nutrition; microbiome; Joint hypermobility syndrome; functional bowel disorders; IBS

Lay Summary (German)

Lead
Joint Hypermobility Syndrome, ein Syndrom charakterisiert durch Hyperlaxizität von Gelenken und Bindegewebe, ist in den letzten Jahren mit Krankheiten aus dem Formenkreis der "funktionellen Magen-Darmerkrankungen" assoziiert worden. Funktionelle Magen-Darmerkrankungen wie der Reizdarm (englisch Irritable Bowel Syndrome, IBS) und die funktionelle Dyspepsie (FD) sind häufig und haben einen relevanten Einfluss auf die Lebensqualität Betroffener.Unser Projekt wird unterliegende Pathologien und assoziierte Erkrankungen untersuchen, um eine bessere Charakterisierung dieser Patienten und allenfalls neue Therapieansätze zu schaffen.
Lay summary

Joint-Hypermobility Syndrome (JHS), ebenfalls charakterisiert als Ehler Danlos Typ III, ist durch Untersuchungskriterien rheumatologischer Expertengruppen durch die Beighton und Brighton-Kriterien klinisch definiert worden. In einem Teil dieser Patienten konnten molekulare Defekte in Strukturproteinen nachgewiesen werden, die zu genannter Hyperlaxizität führen. Da man davon ausgeht, dass diese Strukturdefekte generell das Bindegewebe, also auch ausserhalb von Gelenken, betreffen, zielt unser Projekt auf Veränderungen der Beweglichkeit, des Mikrobioms, der Toleranz von Nahrungsmitteln und entsprechender Behandlungen (antibiotische Behandlung bei bakterieller Überwucherung, angepasste Ernährung bei Unverträglichkeiten).

In teils parallelen, teils nachfolgenden Einzelstudien werden wir Patienten aus unserer Sprechstunde für funktionelle Magen-Darmerkrankungen auf JHS untersuchen. Vergleichend werden wir Patienten aus der hepatologischen Sprechstunde untersuchen, um die Prävalenz in der eher die Allgemeinbevölkerung repräsentierenden Sprechstunde versus unserer Spezialsprechstunde für funktionelle Magen-Darmerkrankungen zu testen. Desweiteren werden wir Unterschiede im Mikrobiom mittels Testung von Stuhlproben und hydrogen-basierten Atemtests, Unverträglichkeit für fermentierbare Kohlehydrate (sogenannte FODMAP's) und Ansprechen auf eine FODMAP-arme Diät untersuchen, Unterschiede in der Behandlung bei Verdacht auf bakterielle Überwucherung herausarbeiten und begleitende psychologische Einflussgrössen messen.

Direct link to Lay Summary Last update: 22.06.2016

Responsible applicant and co-applicants

Employees

Project partner

Publications

Publication
Nutrient Challenge Testing Is Not Equivalent to Scintigraphy−Lactulose Hydrogen Breath Testing in Diagnosing Small Intestinal Bacterial Overgrowth
Schindler Valeria, Huellner Martin, Murray Fritz, Schnurre Larissa, Becker Anton S, Bordier Valentine, Pohl Daniel (2020), Nutrient Challenge Testing Is Not Equivalent to Scintigraphy−Lactulose Hydrogen Breath Testing in Diagnosing Small Intestinal Bacterial Overgrowth, in Journal of Neurogastroenterology and Motility, 26(4), 514-520.
Differentiation of functional gastrointestinal disorders from healthy volunteers by lactulose hydrogen breath test and test mealLHBT differentiates FGID from HV
Schindler Valeria, Giezendanner Stéphanie, Bütikofer Simon, Murray Fritz, Runggaldier Daniel, Schnurre Larissa, Zweig Annina, Fried Michael, Pohl Daniel (2018), Differentiation of functional gastrointestinal disorders from healthy volunteers by lactulose hydrogen breath test and test mealLHBT differentiates FGID from HV, in Journal of Gastroenterology and Hepatology, 1.
Higher prevalence of joint hypermobility in constipation predominant irritable bowel syndrome
Zweig A., Schindler V., Becker A. S., van Maren A., Pohl D. (2018), Higher prevalence of joint hypermobility in constipation predominant irritable bowel syndrome, in Neurogastroenterology & Motility, 30(9), e13353-e13353.

Collaboration

Group / person Country
Types of collaboration
Quasim Aziz / Wingate Institute of Neurogastroenterology Great Britain and Northern Ireland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Magnus Simrén / University of Gothenburg Sweden (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Gerhard Rogler / University Hospital Zurich Switzerland (Europe)
- Research Infrastructure
- Exchange of personnel
Cäcilia Reiner / University Hospital Zurich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Beat Müllhaupt / University Hospital Zurich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
Philip Kaufmann / University Hospital Zurich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
Lukas van Oudenhove / TARGID, Leuven Belgium (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Federation of Neurogastroenterology and Motility Meeting 2018 Poster Liquid test meal combined with lactulose hydrogen breath test allows discrimination between functional dyspepsia and healthy volunteers 29.08.2018 Amsterdam, Netherlands Schindler Valeria; Fried Michael; Pohl Daniel;
United European Gastroenterology Week 2017 Poster Better response to low FODMAP diet in JH negative patients with disorders of gut-brain interaction 28.10.2017 Barcelona, Spain Schindler Valeria; Fried Michael; Pohl Daniel;
Digestive Disease Week 2017 Poster Prevalence of Joint Hypermobility Varies between Subtypes of Irritable Bowel Syndrome 06.05.2017 Chicago, Illinois, United States of America Schindler Valeria; Fried Michael; Pohl Daniel;
Digestive Disease Week 2017 Poster Association Between Prevalence of Fodmap Intolerance According to Nutrient Challenge Testing and IBS Subtypes 06.05.2017 Chicago, Illinois, United States of America Pohl Daniel; Fried Michael; Schindler Valeria;


Associated projects

Number Title Start Funding scheme
154488 The Microbe-Host Interface: Molecular Mechanisms Mediating Protective and Pathological Innate and Adaptive Immune Responses within the Gut 01.11.2014 Sinergia
148422 Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS) 01.04.2014 Cohort Studies Large

Abstract

Irritable bowel syndrome (IBS) is a disorder of gastrointestinal function characterized by abdominal symptoms and pain associated with alterations in bowel habit. The condition impacts on the quality of life of at least 10% of the population, impacts on activities of daily living and is associated with considerable direct and indirect costs to the individual, the health system and society. The etiology of IBS appears multifactorial and several mechanisms, among them mucosal inflammation, abnormal intestinal motility, visceral hypersensitivity and psychological factors, appear to be involved.The underlying pathophysiology, namely Joint Hypermobility Syndrome (JHS), that we wish to study, has recently gained increasing attention in patients with functional bowel disease. Joint Hypermobility Syndrome, nowadays used synonymously with Ehler-Danlos Syndrome, Type III, is characterized by abnormalities in collagen synthesis and is a multisystem disorder with widespread, including abdominal, musculo-scelettal and vegetative, symptoms. Within the proposed project, we aim (1) to explore Joint Hypermobility Syndrome in association with known key players, such as nutrition, in symptom generation (2) to study possible psychological co-factors involved and, (3) finally, to research structural differences immediately translatable in patients’ symptomatology by means of anorectal function and sensitivity. In detail we aim to study pathophysiology in functional bowel patients, focusing on prevalence of JHS, diagnosis of SIBO and antibiotic intervention, mechanisms of nutritional intolerance and interventional diet, as well as underlying changes in the microbiome and psychologic comorbidities. This set of studies has the potential to profoundly change patient management, both on the diagnostic and therapeutic side, assist in patient stratification and open doors to coming trials, especially on JHS, regarding upper gut function (gastroesophageal reflux disease, functional dyspepsia) and multi-disciplinary treatment approaches, including integrative medicine.
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