Community Research and Development Information Service - CORDIS

Periodic Report Summary 1 - NEUROGUT (European Training in Neural Regulation of Intestinal Function)

GOALS AND OBJECTIVES

Functional disorders of the gastrointestinal tract are thought to be due to disorganised "gut-brain interaction" of either afferent or efferent or both pathways in control of intestinal functions. In addition, low-grade inflammation of the intestine, nutritional challenges of the local (intestinal) immune system, and/or post-infectious neuroplastic changes of the enteric nervous system of the gut are believed to be common pathogenetic mechanisms of functional intestinal disorders and link them to other major enteric diseases such as inflammatory bowel diseases. Genetic contributions to the susceptibility to develop functional disorders have been established, and psychological modulators (stress) of its clinical expression have been shown to be effective. Both contribute to efficacy of therapeutic interventions.

Hence, research is needed to establish the links between the various components of the "gut - brain - gut axis" that would allow a better differentiation of these conditions. This is the aim of the ITN "European Training in Neural Regulation of Intestinal Function" (NeuroGut). The subprojects of NeuroGut are arranged along the process of digestion. This process ("digestive circle") illustrates the interconnectivity of all functions along the gut-brain axis. The NeuroGut network therefore consists of internationally leading experts in these research fields, coming from academia and from the private sector, that have designed 14 state-of the-art research subprojects to explore the neuronal and immunological control of gut functions in health and in major functional disorders of the gastrointestinal tract.

They represent the various aspects of neural control of gut functions, especially in functional bowel disorders of "irritable bowel syndrome" type (IBS). Included is the luminal and mucosal challenge of the gut immune system through food intake, processes of inflammation involving the enteric nervous system (ENS), thereby affecting gut motility, secretion and absorption, leading to visceral sensations, that may impress as symptoms in functional bowel disorder (FBD) (pain, hypersensitivity, dyspepsia, diarrhea, constipation). These symptoms are transmitted via the spinal and vagal afferent branches of the autonomic nervous system (ANS) to the brain - thereby affecting food intake, the psychological state of patients, and chronification of the disease state.
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MAIN RESULTS ACHIEVED

Following recruitment of 11 ESRs and 3 ERs, the work started early 2014 with training the ESRs and ERs is the respective technologies of the laboratories involved, and with basic training across the settings, e.g. trainings schools in business management (Entrepreneurship Academy), genetics, and microbiota analysis. All ESRs and ERs already presented their first "own" data not only at the annual meetings held so far, but also at national and international conferences, e.g. the European Neurogastroenterology and Motility Meeting, held in Istanbul in June 2015.

WORK PACKAGE 1

Subproject (SP) 1 published a review and established a fMRI measurement routine for functional dyspepsia patients & volunteers.
SP8 analyzed a large patient cohort with detailed phenotype measurements and found three distinct subgroups of patients.
SP10 used an established visceral hypersensitivity model (oesophageal acidification) and explored stress models and drug modification on sensitivity.
SP11 established a magnetoencephalographic brain recording paradigm for studying stress responses (cyberball) to investigate probiotic and antibiotic treatment effects in patient and controls.

WORK PACKAGE 2

SP2 developed, established and validated a model of lactose treatment to induced visceral hypersensitivity in animals.
SP3 collected and supernatants from IBS and IBD patients and healthy volunteers for mass spectrometry protease analysis.
SP5 succeeded in phenotyping and genotyping changes in nerves supplying the gut mucosa of patients with severe IBS.
SP7 found that bacterial products are potent modulators of intestinal nerve activity, aiming to identify candidate substances that mediate the inhibitory of supernatants on nerve activity.

Work PACKAGE 3

SP4 demonstrated that hiatus hernia may occur during exercise in the healthy volunteers, shedding light on its assumed relevance in GORD.
SP6 developed an animal (mouse) model for post-infectious IBS following supernatant analysis of biopsies from PI-IBS patients.
SP9 developed a new method based on endoluminal abdominal MRI analysis that does not involve radiation and may allow sequential studies on the dynamics of abdominal structures.

WORK PACKAGE 4

SP12 applied deep computer learning techniques to endoluminal images from capsule endoscopy.
SP13 published a report on the role of serotonin in inflammatory processes and cleared in a proof-of-concept study the role of 5-HT receptors on visceral hypersensitivity in animal model.
SP14 published a systematic review on probiotic treatment in IBS, and initiated a pilot study comparing probiotic to hypnotherapeutic therapy in children with IBS.

While the PIs of the NeuroGut network continued their traditional collaboration - that is mirrored in more than 90 papers in PUBMED with two or more of the NeuroGut PIs as authors - first publications were accepted from ESRs and ERs within their local network as well as across the NeuroGut subprojects:

P.Enck, Q.Aziz, G.Barbara, A.D.Farmer, S.Fukudo, E.A.Mayer, B.Niesler, E.M.M.Quigley, M.Rajilic-Stojanovic, M.Schemann, J.Schwille-Kiuntke, M.Simren, S.Zipfel and R.C.Spiller: Irritable Bowel Syndrome. Nature Reviews Diseases Primers 2016 (in press)

L.Houghton, K.A.Wensaas, M.Simrén, L.v.Oudenhove, Q.Aziz, D.Dumitrascu, V.Drug, M.Vassallo, D.Pohl, A.Polster, L.Pojskic, M.Stengel, B.Niesler, and G.Boeckxstaens: How to standardize the process of phenotyping IBS patients: a consensus report Neurogastroenterology and Motility 2016 (in press)

Almost the complete NeuroGut partners were also involved in submission of the H2020 grant proposal “GEMINI: Genes and micobiota are nested in IBS”.
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WEBSITE: http://www.neurogut.eu
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RESEARCH COORDINATOR: Prof. Paul Enck, Eberhard Karls Universität Tübingen, Department of Internal Medicine VI, Psychosomatic Medicine and Psychotherapy, Osianderstr. 5, D - 72076 Tübingen, Germany, Email: paul.enck@uni-tuebingen.de

PROJECT MANAGEMENT: Dr. Sigrid Diether, Eberhard Karls Universität Tübingen, Centre for Ophthalmology, Research Management Unit, Frondsbergstrasse 23, D - 72070 Tübingen, Germany, Email: sigrid.diether@uak-swm.de

Reported by

EBERHARD KARLS UNIVERSITAET TUEBINGEN
Germany

Subjects

Life Sciences
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