# 5th International Symposium on Functional GI disorders



## eric (Jul 8, 1999)

FYI http://www.iffgd.org/symposium2003report.html


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## Mike NoLomotil (Jun 6, 2000)

Yes indeed some important pardigm shifting is coming along in the area of understanding neuroimmunogastric relationships in IBS mechanisms, just took some time for the process of paradigm shIft to begin.Excerpted from summaries of presentations made during 2003 Digestive Disease Week:From:Basic Principles -- Brain-Gut Moderators: Emeran Mayer MD; Robin Spiller MD. Panel: Robin Spiller MD; Jackie Wood PhD; George Chrousos MD; Yvette Tachï¿½ PhD; Lisa Goehler PhD; G.F. Gebhart PhD; Emeran Mayer MD. "One of the more exciting areas of recent research relates to the basic and translational aspects of the effects of stress on inflammation, cytokine and immune modulation, and pain. (Cytokines are a type of protein released by cells of the immune system, which act through specific cell receptors to regulate immune responses.) This series of presentations address three important research areas in the field of functional GI disorders, which have recently attracted considerable attention: the role of immune activation in the gut and the interactions of the gut immune and nervous systems; the role of the central nervous system in the regulation (modulation) of pain perception (nociception); and the emerging field of animal models with relevance for functional GI disorder research. This section demonstrates the rapid progress seen in the last few years in better understanding of basic mechanisms, in particular the neuroimmune interactions underlying symptom generation in patients with "functional" GI disorders. "and further on&#8230;"While we often talk about how the brain -- influenced for example by arousal and/or psychosocial factors -- can affect immune function, the reverse is also true. Immune activation, following infection for example, can influence brain function. Lisa Goehler, University of Virginia discussed Cytokines and Vagal Afferents: Immune Signaling to the Brain. Cytokines are substances that are produced by white blood cells to regulate certain functions during inflammatory and immune responses. The vagus is a nerve made of both sensory and motor fibers that innervates nearly every internal organ. The gastrointestinal (GI) tract, along with the lungs and liver, is an area of tissue that most commonly comes in contact with microorganisms (pathogens), such as bacteria or viruses, capable of activating an immune response. Cytokine mediators activate neurons that convey messages from tissue to the brain (afferent neurons) through the vagus nerve. The GI tract is richly supplied with vagal afferents that can signal immune activation in the tissue. This process may underlie the mechanism that causes individuals to feel sick. The concept of "sickness symptoms" is not always recognized. The cytokine inflammatory and immune mediators distributed throughout the body (peripheral), which appear to interact through vagal pathways, have systemic effects that manifest as symptoms in the body. (Mediators are substances released from cells to regulate immune responses.) Such symptoms include fever, increased sensitivity to pain, loss of appetite, and decreased desire for social interaction. The process may provide the basis for a role of the vagus as an interface between the site of the immune response and the brain that results in symptoms of altered mood, including anxiety or depression, that are sometimes associated with gastrointestinal disease.[4] "___________________________________________This is very exciting, to see these principals of symptom generation in IBS patients, long studied and used as the basis for treatment of IBS patients in Europe and often dismissed as irrelevant to so called IBS, are finally coming to the fore in American GI Symposia. Catching up is hard to do but it is nice to see it beginning. The integration of an understanding that mediator release is not the sole relam of stress reponse is also important, and is also at least recognized: peer reviewed journals have already long ago published confirmation of mechanisms described in standard immunology textbooks for a decade: cell mediated reactions are a primary mechanism of regulating the central and peripheral nervous system, and this occurs not only in repsonse to pathogen but to food antigen as well&#8230;without involvement of specific antibodies to any provoking challnge.Several studies confirming the role of aberrant immune response to food challenge, resulting in local and systemic release of proinflammatory mediators and proalgesic mediators, especially cytokines, have been published in the last 10 years, and were systematically overlooked by many. Clearly it is becoming clearer that one cannot look at IBS through the same paradigms forever, especially when those paradigms are not leading to succesful treatment.These facts regarding cellular mediators as symptom generators have often been referenced, as have these mechanisms of local and systemic symptom generation, in explaining the physiologic basis for the LEAP Approach to Disease Management of Diarrheic IBS victims.It is intriguing that the very systemic immunocyte reactions referenced as possibly accounting for the very same "sickness syndrome" reported by IBS patients and relieved by oligoantigenic diet is finally "noted" as "possibly" linked to cytokines. These reactions have long been shown to manifest themselves via Loss of Oral Tolerance to specific foods or additives in patients presenting with IBS symptoms. These systemic effects of cytokines released in food intolerant patients were quantified and published most recently in 2000 in a major journal&#8230;Lancet 2000 Jul 29;356(9227):400-1Relation Between Food Provocation and Systemic Immune Activation in Patients with Food Intolerance.Jacobsen MB, Aukrust P, Kittang E, Muller F, Ueland T, Bratlie J, Bjerkeli V, Vatn MH.Section of Gastroenterology, Rikshospitalet, University of Oslo, N-0027 Oslo, Norwayb Section of Clinical Immunology and Infectious Diseases, Rikshospitalet, University of Oslo, N-0027 Oslo, Norwayc Section of Endocrinology, Rikshospitalet, University of Oslo, N-0027 Oslo, Norwayd Medical Department and Research Institute of Internal Medicine, Rikshospitalet, University of Oslo, N-0027 Oslo, Norwaye Medical Department, Vestfold Sentral Hospital, Tï¿½nsberg, Norway In fact this specific mechanism, the basis for Mediator Release Testing in the LEAP DM programs, is at present under intensive scrutiny using the latest technology to quantify the array oand variance of systemic cytokines released in response to oral challenge in both IBS and Migraine subjects. This project should result in remarkable findings, more comprehensive than those in the above investigation, giving quantitative confirmation of the existence of this mechanism as a common and essential mechanism in global IBS symptomology. This should be complete and ready for publication prior to the time of Digestive Disease Week 2004! The preliminary results of the trial examinations already completed (unpublished) confirm quantitatively the changes in plasma cytokine levels in response to oral challenges in both IBS and Migraine subjects.Appraciet these mechanisms and one can understand why patient specific oligoantigenic diets, as developed in the LEAP Program based on testing for inappropriate release of mediators, is effective at symtomatic prophylactic relief in these patients.MNL


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## Guest (Oct 19, 2003)

Bump


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