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The Science of IBS
From Medscape General Medicine™
MedGenMed Gastroenterology
IBS -- Review and What's New
Given the lack of definitive organic markers for IBS, the absence of a unifying hypothesis regarding its underlying pathophysiology is not surprising. Nevertheless, important advances in research made during the past 50 years have brought us closer than ever to understanding the numerous putative etiologic factors involved in this multifaceted disorder, including environmental factors, genetic links, previous infection, food intolerance, and abnormal serotonergic signaling in the GI tract.
Environmental Influences
Although a patient's psychological state may influence the way in which he or she presents, copes with illness, and responds to treatment, no evidence supports the theory that psychological disturbances are the cause of IBS.[39,40] The biopsychosocial model proposed by Engel takes into account the interplay between biologic, psychological, and social factors.[41] This model proposes that there is an underlying biologic predisposition for IBS that may be acted on by environmental factors and psychological stressors, which contribute to disease development, the patient's perception of illness, and impact on treatment outcomes.[42,43]
Studies evaluating the role of acute stress have shown that stress can result in release of stress-related hormones that affect colonic sensorimotor function (eg, corticotropin-releasing factor [CRF] and inflammatory mediators [eg, interleukin (IL)-1]), leading to inflammation and altering GI motility and sensation.[44] For example, CRF-1 receptors located in the central nervous system (CNS) and gut can affect colonic motility, epithelial water transport, and gut permeability.[45] Sagami and colleagues[46] determined that the peripheral administration of a nonselective corticotropin-releasing hormone (CRH) receptor antagonist improved GI motility, visceral perception, and negative mood in response to gut stimulation in patients with IBS. These findings suggest that CRH may play an important role in the pathophysiology of IBS.
Genetics
Studies with twins have shown that IBS is twice as prevalent in monozygotic twins as in dizygotic twins.[47-49] Limited research on familial aggregation has found that individuals who have a family member (other than a spouse) with a history of abdominal pain or bowel disorder have more than 2-fold increased odds of having IBS. It is likely that environmental influences may help explain this finding (eg, awareness of the symptom status of family members may make sufferers more open to discussing their symptoms and seeking help for the condition).[50] Preliminary findings also suggest that IBS may be associated with select gene polymorphisms, including those in IL-10, G-protein GNb3, alpha adrenoceptor, and serotonin reuptake transporter (SERT).[47, 51-54] Despite these potential links, however, conclusive evidence for a genetic basis for IBS has not been established.
http://www.medscape.com/viewarticle/532089_3
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The Science of IBS
From Medscape General Medicine™
MedGenMed Gastroenterology
IBS -- Review and What's New
Postinfectious IBS
The presence of postinfectious (PI)-IBS, referring to the development of IBS symptoms -- particularly abdominal pain and diarrhea -- shortly after an enteric infection, is based on research from prospective studies in which IBS symptoms developed in 7% to 32% of patients after they recovered from bacterial gastroenteritis.[52,55,56] Specific risk factors for the development of PI-IBS have been identified, including younger age, female sex, presence of severe infectious gastroenteritis for a prolonged period, use of antibiotics to treat this infection, and presence of concomitant psychological disorders (eg, anxiety).[39,52,55,57] Difficulty in downregulating intestinal inflammation in the colonic mucosa has been suggested as a potential underlying mechanism in this condition.[52] Also suggested as a potential underlying mechanism is the presence of colonic changes shown in patients with PI-IBS compared with controls, including increased gut permeability, increased mucosal enterochromaffin cell production, and increased concentration of mast cells and T lymphocytes in the gut mucosa.[39,52,55,57] Despite considerable evidence linking IBS with an inflammatory etiology (perhaps triggered by enteric infection), in a controlled trial of patients with PI-IBS, anti-inflammatory treatment with prednisolone was not more effective than placebo in improving patient symptoms.[58] The true role of prior infection as a key factor in PI-IBS remains to be established.[59]
The use of probiotics (products containing live or attenuated bacteria that have a positive effect on the host) in alleviating symptoms in patients with PI-IBS is an area of recent focus.[60,61] The potential utility of probiotics in this setting stems from their antibacterial, antiviral, and immune-modulating properties; their ability to modify intestinal flora; and their potential to enhance intestinal mucus secretion or influence stool consistency or volume and gas handling.[60] The number of studies evaluating the efficacy of probiotic preparations in patients with IBS is limited but growing.[60-68] Because trials vary in study design, dose, and strain (Lactobacillus and Bifidobacteria alone or in combination; mixture of Lactobacillus, Bifidobacteria, and Streptococcus), direct comparison of results is challenging. Overall, some degree of IBS symptom improvement has been demonstrated in symptoms such as abdominal pain,[65,66] bloating,[63,66] gas,[66] and daily symptom scores.[62,65] O'Mahoney and colleagues[60] have recently demonstrated that results with the Bifidobacterium infantis strain are particularly promising. In a separate analysis, these investigators showed that the baseline characteristics of urgency and hard stool increased the odds ratio of response to this strain, whereas straining and alcohol consumption reduced the likelihood of response.[69,70] The ultimate place in therapy of probiotics in IBS remains to be elucidated.
Small Intestinal Bacterial Overgrowth
The presence of a higher than usual population of bacteria in the small intestine (leading to bacterial fermentation of poorly digestible starches and subsequent gas production) has been proposed as a potential etiologic factor in IBS.[71] Pimentel and colleagues have shown that, when measured by the lactose hydrogen breath test (LHBT), small intestinal bacterial overgrowth (SIBO) has been detected in 78% to 84% of patients with IBS.[71,72] However, the accuracy of the LHBT in testing for the presence of SIBO has been questioned.[73] Sensitivity of the LHBT for SIBO has been shown to be as low as 16.7%, and specificity approximately 70%.[74] Additionally, this test may suboptimally assess treatment response.[75] The glucose breath test has been shown to be a more reliable tool,[76] with a 75% sensitivity for SIBO[77] vs 39% with LHBT for the "double-peak" method of SIBO detection.[74] In a recently conducted retrospective study involving review of patient charts for the presence of gastrointestinal-related symptoms (including IBS) in patients who were referred for glucose hydrogen breath tests for SIBO, of 113 patients who met Rome II criteria for IBS, 11% tested positive for SIBO.[78] Thus, results demonstrated that IBS symptoms are often unrelated to the presence of SIBO. Despite the controversy regarding the contribution of SIBO to the underlying pathophysiology of IBS and its symptoms, short-term placebo-controlled clinical studies with select antibiotics, including neomycin and rifaximin, have demonstrated symptom improvement in IBS patients.[61,72,79] Antibiotics may therefore have potential utility in select subgroups of IBS patients in whom SIBO contributes to symptoms. However, the chronic nature of IBS symptoms often leads to the need for long-term treatment. Given the fact that long-term use of antibiotics is generally undesirable, the place of antibiotics in IBS therapy remains to be established.[73]
http://www.medscape.com/viewarticle/532089_3
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Restricted Fetal Growth Linked to Irritable Bowel Syndrome
NEW YORK (Reuters Health) Sept 28 - Findings from a new study suggest that restricted fetal growth is a risk factor for the development of irritable bowel syndrome (IBS) later in life.
Nutrition during fetal life is thought to play a role in a number of chronic diseases, including diabetes, hypertension, and coronary heart disease. In the present study, Dr. May-Bente Bengston and colleagues determined if this was also the case for IBS by looking at the impact of intrauterine growth on disease outcomes.
The study, which is reported in the September 28th online issue of Gut, involved 12,700 Norwegian twins, born between 1967 and 1979, who completed a disease questionnaire that included IBS. Disease discordance in monozygotic twins was evaluated to assess the link between intrauterine growth and IBS.
IBS concordance in monozygotic twins was 22.4% compared with 9.1% in dizygotic twins, the report indicates (p = 0.011). Genetic factors appear to contribute to IBS in females to a greater extent than in males.
A birth weight below 1500 g was linked to a 2.4-fold increased risk of IBS compared with a weight exceeding 2500 g. Moreover, the disease appeared about 8 years earlier in lower weight groups than in higher weight groups.
Among monozygotic twins with birth weights lower than 2500 g, IBS was significantly more common among lighter twins than heavier ones.
"These results may suggest a new classification of patients into subgroups based on age at onset of symptoms, sex, familial resemblance, and birth weight, to improve our understanding of the pathophysiological mechanisms of IBS," the researchers conclude.
Gut 2006
http://www.medscape.com/viewarticle/545241
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Irritable Bowel Syndrome Linked to Migraine, Fibromyalgia, and Depression
NEW YORK (Reuters Health) Oct 06 - Findings from a large study indicate that patients with irritable bowel syndrome (IBS) are at increased risk for migraine, fibromyalgia, and depression.
Previous research has linked IBS with these disorders, but much of the supporting data has come from case reports or from small clinical practices, lead author Dr. J. Alexander Cole and colleagues, from Boston University, note.
Methodologic issues, such as the lack of a reference group and the inability to fully control for confounding factors, prevented these studies from reaching definitive conclusions.
The current study, in the September 28th issue of BMC Gastroenterology, involved more than 125,000 subjects and did include a reference cohort. The subjects were drawn from a large US health plan and had an ICD-9 code for either IBS or routine medical care (non-IBS cohort).
Compared with non-IBS patients, those with the condition were 60% more likely to have any one of the three target disorders, the report indicates. The elevated risks for depression, migraine, and fibromyalgia were 40%, 60%, and 80%, respectively.
The current findings support previous reports, which have promoted speculation that all four disorders share an underlying biological mechanism, the authors conclude.
BMC Gastroenterol 2006.
http://www.medscape.com/viewarticle/545683
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Traveler's Diarrhea May Boost Risk of Irritable Bowel Syndrome
NEW YORK (Reuters Health) Oct 11 - People who experience traveler's diarrhea appear to be at significantly increased risk of subsequently suffering from irritable bowel syndrome (IBS), Israeli researchers report in the October 1st issue of Clinical Infectious Diseases.
Dr. Edy Stermer of B'nai Zion Medical Center, Haifa and colleagues came to this conclusion after studying travelers who had visited a traveler's clinic for counseling and vaccinations before their trips and had contacted the center again after their return.
The researchers studied 483 travelers, most of whom (84%) visited Asia. Their mean age was 30.8 years. In all, 412 were followed up after returning home and 405 were contacted 6 months after their return.
The team found that the rate of IBS in travelers who had had diarrhea during their trip (13.6%) was more than 5 times greater than in was in participants who had no such diarrhea (2.4%).
Women appeared to be more likely to experience IBS. They accounted for 60.9% of the IBS group, but only 46.7% of the entire cohort.
Among other findings, the researchers conclude, were that in the diarrhea group, abdominal pain was significantly more common in those who developed IBS and the duration of diarrhea was significantly greater.
Clin Infect Dis 2006;43:898-901.
http://www.medscape.com/viewarticle/545879
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From Medscape Gastroenterology
Expert Interview
Advances in the Treatment and Understanding of Chronic Constipation and IBS-C: An Expert Interview With Lawrence R. Schiller, MD
Editor's Note:
Irritable bowel syndrome with constipation (IBS-C) and chronic constipation, two of the most common functional disorders of the gut, place a considerable burden on patients and society alike. Indeed, symptoms of both of these gastrointestinal motility disorders are chronic, sometimes severe, and often respond poorly to traditional therapeutic strategies. Inadequate therapy can lead to reduced quality of life, polypharmacy, and increased utilization of healthcare resources. Medscape spoke with Lawrence R. Schiller, MD, Program Director, Gastroenterology Fellowship, Baylor University Medical Center, Dallas, Texas, to discuss the clinical impact of these functional bowel disorders, with a view toward current and emerging therapies, as framed by data presented during the American College of Gastroenterology (ACG) 2006 Annual Scientific Meeting and Postgraduate Course.
Medscape: Given the current state of the field, what do you perceive are the most important barriers to the optimal management of patients with IBS-C and chronic constipation?
Dr. Schiller: Currently, the greatest barriers to optimal management of functional disorders, in general -- and chronic constipation and IBS-C, in particular -- are recognition by patients that something can be done to help their chronic symptoms and recognition by physicians that their patients have these disorders and that more can be done for them. The first limits the number of patients who come to physicians to avail themselves of treatment, and the second limits the application of modern treatments to this group of patients.
For example, we know from good population surveys that approximately 15% of the adult population in the United States meet the criteria for chronic constipation,[1] and that almost half of these individuals are unhappy with the treatments that they have been using. However, only a fraction of this group consults with physicians about constipation.[2] This means that many patients have unmet needs with regard to their bowel habits.
Likewise, we now have agents that can improve symptoms -- and quality of life -- in up to 70% of these constipated patients; however, physicians fail to recognize the presence of the disorder, its impact on patients, and the fact that traditional remedies leave many patients suffering with symptoms.
http://www.medscape.com/viewarticle/545988
Medscape Gastroenterology. 2006;8(2) ©2006 Medscape
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The Northwestern Center for Functional GI & Motility Disorders is conducting a research study looking at attitudes and opinions about people who have Irritable Bowel Syndrome (IBS). The purpose of this study is to develop a questionnaire that would measure social stigma toward those who are affected by IBS that could be used by health care providers to address this important area of quality of life. We are seeking volunteers to complete 3 online questionnaires that include questions about demographic information, attitudes others may have had toward you because you have IBS, and how open you are about your condition.
If you would like to participate, please visit this link: http://www.northwesternmotility.com/currentstudies.html#Stigma_IBS
If you have any questions or concerns about this research, please contact the study coordinator at (312) 694-7717 or FGIDResearch@northwestern.edu.
About the Northwestern Center for Functional GI & Motility Disorders. The Northwestern Center for Functional Gastrointestinal and Motility Disorders was created to provide comprehensive evaluation and treatment for patients with difficult and often poorly explained digestive symptoms. Our mission is to advance the understanding and treatment of functional gastrointestinal and motility disorders through an integrated approach to patient care, research, training and education. In addition to the evaluation and treatment of functional and digestive motility disorders, we also conduct studies on the physiological and psychosocial mechanisms that often underlie these conditions. Our group has clinical and research interests in quality of life, health outcomes and stigma related to functional and digestive motility disorders as well as novel pharmacologic and behavioral therapies to treat these conditions.
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Heather is the Administrator of the IBS Message Boards. She is the author of Eating for IBS and The First Year: IBS, and the CEO of Heather's Tummy Care. Join her IBS Newsletter. Meet Heather on Facebook!
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Familial Aggregation in Constipated Subjects in a Tertiary Referral Center
Authors: Chan, Annie O.O.1; Hui, Wai M.1; Lam, Kwok F.2; Leung, Gigi1; Yuen, Man F.1; Lam, Shiu K.1; Wong, Benjamin C.Y.1
Source: The American Journal of Gastroenterology, Volume 102, Number 1, January 2007, pp. 149-152(4)
Publisher: Blackwell Publishing
Abstract:
OBJECTIVES: Clinical observation showed that there is family aggregation in constipated subjects, but formal data are lacking. This prompted us to conduct a formal family study in constipated subjects.
METHODS:Constipated subjects (probands) were identified according to the Rome II and Chinese constipation questionnaire criteria, healthy subjects were chosen as controls. Living first-degree relatives (parents, siblings, and children) and spouses (as internal controls) from both groups were identified. The questionnaire on Rome II criteria was given to the relatives either through the index subjects or by mail. The questionnaire was received by mailing back or through the index subjects. Any nonresponders were chased.
RESULTS:There were 132 probands with constipation and 114 controls. The Rome II questionnaire was sent to a total of 677 relatives of the probands and 591 of the controls. Relatives were comparable in mean age, sex distribution, family size, and marital status in the two groups. Constipation prevalence was 16.4% in probands' relatives versus 9.1% in controls' relatives, i.e., 13% in the relatives from both proband and controls.
Among the constipated relatives, 6.3%versus 9.3% of the relatives were spouses of the probands and controls (P= 0.5). Subjects with more family members having constipation will have higher risk of constipation: OR 2.02, CI 1.14-3.65, P= 0.0177 for at least one family member; OR 3.99, CI 1.86-9.23, P= 0.0006 for at least two family members.
CONCLUSIONS:Familial aggregation of constipation occurs, supporting a genetic or intrafamilial environment component.
(Am J Gastroenterol 2007;102:149-152)
http://www.ingentaconnect.com/content/bsc/ajg/2007/00000102/00000001/art00025;jsessionid=7iupa7t1jrskc.victoria
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Physical activity and intestinal gas clearance in patients with bloating
Am J Gastroenterol. 2006; 101(11):2552-7 (ISSN: 0002-9270)
Villoria A; Serra J; Azpiroz F; Malagelada JR
Digestive System Research Unit, University Hospital Vall d'Hebron, Autonomous University of Barcelona, Barcelona, Spain.
BACKGROUND: Patients complaining of abdominal bloating have impaired tolerance and clearance of intestinal gas loads. Mild exercise enhances intestinal clearance and prevents retention of intestinal gas loads in healthy subjects. Our aim was to evaluate the putative beneficial effects of physical activity in patients with abdominal bloating. METHODS: In eight patients complaining of bloating, seven with irritable bowel syndrome, and one with functional bloating, according to Rome II criteria, a gas mixture was continuously infused (12 mL/min) into the jejunum for 120 min with simultaneous duodenal lipid perfusion (1 kcal/min). Gas evacuation, perception (0-6 scale), and abdominal girth were measured at 15-min intervals. Paired studies were randomly performed in the supine position during intermittent pedaling (5 min with 3-min rest intervals at 40 rpm and 0.15 kp load) versus rest (as control). RESULTS: During rest, a significant proportion of the gas infused was retained in the gut (45 +/- 9%, P < 0.01 vs basal), but retention was significantly lower during exercise (24 +/- 7%, P < 0.05 vs rest). Gas retention during rest was associated with significant abdominal symptoms (3.6 score; P < 0.01 vs basal), and symptoms also improved during exercise (2.8 score, P < 0.05 vs rest). During the test, patients developed abdominal distension, which was related to the volume of gas retained (r = 0.68, P < 0.05). CONCLUSION: Mild physical activity enhances intestinal gas clearance and reduces symptoms in patients complaining of abdominal bloating.
http://www.medscape.com/medline/abstract/17029608
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The Annenberg School for Communication at the University of Southern California is conducting a research study looking at interpersonal communication patterns of people who have been diagnosed with Irritable Bowel Syndrome (IBS).
The purpose of this study is to understand the possible link between IBS symptom severity and how one communicates with their closest relational partner. We are seeking volunteers to complete an approximately 15-minute online survey that includes questions about demographic and relational information, interpersonal communication patterns with a close relational partner, and severity of IBS symptoms.
To qualify for this study, you must meet the following criteria:
1. Be diagnosed by a physician with IBS at least three months ago 2. Consider IBS to be your primary health problem 3. Not be diagnosed by a physician with any other gastrointestinal disorder 4. Not currently be pregnant
The first 150 IBS-diagnosed participants will receive a $5 Amazon.com gift card via email once they have completed the online survey.
If you would like to participate, please click on this web address: http://www.surveymonkey.com/s.asp?u=436613076272
If you have any questions or concerns about this research, please contact the study coordinator at bevanj@usc.edu.
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Heather is the Administrator of the IBS Message Boards. She is the author of Eating for IBS and The First Year: IBS, and the CEO of Heather's Tummy Care. Join her IBS Newsletter. Meet Heather on Facebook!
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