Research In Functional Gastrointestinal Disorders Research Articles

A biomarker panel and psychological morbidity differentiates the irritable bowel syndrome from health and provides novel pathophysiological leads

The development of a reliable biomarker for irritable bowel syndrome (IBS) remains one of the major aims of research in functional gastrointestinal disorders (FGIDs) and is complicated by the absence of a perfect reference standard. Previous efforts based on genetic and immune markers have showed promise, but have not been robust. To evaluate an extensive panel of gene expression and serology markers combined with psychological measures in differentiating IBS from health and between subtypes of IBS. Of subjects eligible for analysis (N = 244), 168 met criteria for IBS (60 IBS-C, 57 IBS-D and 51 mixed), while 76 were free of any FGID. A total of 34 markers were selected based on pathways implicated in pathophysiology of IBS or whole human genome screening. Psychological measures were recorded that covered anxiety, depression and somatisation. Models differentiating disease and health were based on unconditional logistic regression and performance assessed through area under the receiver-operator characteristic curve (AUC), sensitivity and specificity. The performance of a combination of 34 markers was good in differentiating IBS from health (AUC = 0.81) and was improved considerably with the addition of four psychological markers (combined AUC = 0.93). Of the 34 markers considered, discrimination was derived largely from a small subset. Good discrimination was also obtained between IBS subtypes with the best being observed for IBS-C vs. IBS-D (AUC = 0.92); however, psychological variables provided almost no incremental discrimination subtypes over biological markers (combined AUC = 0.94). A combination of gene expression and serological markers in combination with psychological measures shows exciting progress towards a diagnostic test for IBS compared with healthy subjects, and to discriminate IBS-C from IBS-D.

Development of Korean Rome III Questionnaire: What Will We Do With Korean Rome III Questionnaire?

Functional gastrointestinal disorders (FGIDs) are common in clinical practice and in communities around the world, including Korea. In 2006, definitions and classifications of FGIDs were revised in Rome III. The major points of the Rome III include: (1) changes in the time frame for diagnosis of FGIDs from 12 months to 6 months for the onset, and from 6 months to 3 months for the activity of the symptoms; (2) changes in functional dyspepsia (FD) to postprandial distress and epigastric pain syndromes (PDS and EPS), focusing on FD symptoms with four major symptoms such as bothersome postprandial fullness, early satiation, epigastric pain and epigastric burning; (3) more restrictive criteria for functional disorders of the gallbladder and sphincter of Oddi; and (4) revision in subtyping irritable bowel syndrome (IBS) from an unclear definition to a definition using stool consistency.1,2 Overlapping of FGIDs or subtypes is permitted in Rome III, therefore, Rome III criteria provide a less restrictive framework for symptom-based diagnosis. A validated questionnaire relating to the diagnosis of FGIDs is crucial to assess the prevalence of FGIDs in epidemiologic studies or enroll patients in clinical trials. A simple translation of a published questionnaire usually fails to contain the original meaning because of language and cultural differences.3 Therefore, a systematic translation and the cross-cultural adaptation process are essential for research using questionnaires. Cross-cultural translation involves adaptation of the translation to the language and culture of the population in which the questionnaire will be used. It is important since comparative studies can only be carried out between different countries and ethnic groups if the translated study instrument is valid cross culturally.4 Systemic translation and independent back translation are essential for accurate translation of the original source. Rome III questionnaire was translated into several languages.2,4 In the issue of this journal, Song et al5 nicely reported the Korean Rome III questionnaire (Rome III-K) through structural translational processes, which is a valid and reliable tool for use in the Korean speaking population and it revealed good test-retest reliability and satisfactory construct validity. What will we do with validated Rome III-K? The further step is that its application into clinical setting or clinical/epidemiological research. Several epidemiological studies and clinical trials should now be conducted using the first Korean instrument for diagnosing FGIDs. Actually a few studies were already performed with Rome-III Questionnaire in Korea. Among these, Park et el6 showed that Rome III questionnaire was useful in defining the FGID patients into the functional disorders in Korea. In a recent prevalence study on FD in Korea using the Rome III criteria, 13.4% of community respondents reported dyspepsia.7 Of these FD cases, 47% were classified as PDS, 26% as EPS, and 27% as overlap syndrome.7 Upper and lower gastrointestinal symptoms commonly overlap and FGIDs are related to psychological disorders. From those 2 studies, the prevalence of EPS is relatively low; the possible explanation is as follows. First, the Rome III criteria for EPS are relatively strict. Also low prevalence of EPS could be influenced by the difficulty in understanding the meanings between heartburn and epigastric burning in Korean language. In addition, overlap FGIDs were found to be common by Rome III criteria which may limit its wide application. From this background there is a great need for validation and standardization in FGID research. Although Rome III criteria are primarily used for research standardization, application in clinical studies will require a greater simplicity.8 Although the criteria are useful in diagnosing and classifying FGID patients, it is very difficult to diagnose all the syndromes based on the Rome III criteria in clinical basis. In addition, Rome III questionnaire are useful in the presumption that organic diseases have been excluded. However, most important thing is whether it has the validation power to differentiate FGIDs from organic diseases, avoiding the need for investigation of organic diseases. This might prove the real clinical utility of Rome III questionnaire. In conclusion, cross-culturally translated Rome III-K will be useful in clinical and epidemiologic research. Is it a more accurate way of diagnosing FGIDs, and distinguishing organic diseases compared with old questionnaires. Further investigation is needed.

Taming the Irritable Bowel

This narrative review covers the mechanisms of actions of trendy drugs approved for or proposed for calming the irritable bowel. Many drugs that target functional gastrointestinal disorders (FGIDS), which includes IBS, have their actions in the enteric nervous system (i.e., the brain-in-the-gut). The in-depth insight into fundamental neurophysiology, which is essential for understanding how the drugs act to achieve their effects, is covered from a neurogastroenterological view point. Pharmacotherapeutic research in FGIDS, which is now lagging, is focused mainly on symptom control. Major progress will require a change to orientation on the malfunction underlying each of the symptoms that constitute Manning, Rome I and Rome II symptom-based criteria for FIGD diagnoses. A high incidence of autoimmune degenerative neuropathy in the enteric nervous system occurs in IBS and is postulated to be the cause of symptoms emerging from failure of normal neural control of motility, blood flow and secretory glands, in concert with sensitization of spinal and vagal sensory mechanisms.

Taming the Irritable Bowel

This narrative review covers the mechanisms of actions of trendy drugs approved for or proposed for calming the irritable bowel. Many drugs that target functional gastrointestinal disorders (FGIDS), which includes IBS, have their actions in the enteric nervous system (i.e., the brain-in-the-gut). The in-depth insight into fundamental neurophysiology, which is essential for understanding how the drugs act to achieve their effects, is covered from a neurogastroenterological view point. Pharmacotherapeutic research in FGIDS, which is now lagging, is focused mainly on symptom control. Major progress will require a change to orientation on the malfunction underlying each of the symptoms that constitute Manning, Rome I and Rome II symptom-based criteria for FIGD diagnoses. A high incidence of autoimmune degenerative neuropathy in the enteric nervous system occurs in IBS and is postulated to be the cause of symptoms emerging from failure of normal neural control of motility, blood flow and secretory glands, in concert with sensitization of spinal and vagal sensory mechanisms.

Post-Infectious Irritable Bowel Syndrome, an Inflammation-Immunological Model with Relevance for Other IBS and Functional Dyspepsia

This review presents studies that support an inflammation-immunological model for the pathogenesis of post-infectious irritable bowel syndrome (IBS), and highlights recent studies that support a similar disease model in non-post-infectious IBS, in particular, diarrhoea-predominant IBS, as well as in post-infectious functional dyspepsia. These recent studies are highlighted to demonstrate that one line of research in functional gastrointestinal disorders has moved away from the old psychosomatic concepts. It is hoped that this will encourage future students of this field to explore the role of immunological events.

The challenge of cross‐cultural, multi‐national research: potential benefits in the functional gastrointestinal disorders

The increasing interest in research in irritable bowel syndrome (IBS) and other functional gastrointestinal disorders (FGIDs), taken together with the growing sophistication of communication technology, makes cross-cultural, multi-national research a feasible endeavour. The aim of this study is to encourage collaborative cross-cultural studies in FGIDs by discussing relevant methodological issues, and by suggesting potential areas in which cross-cultural research can make a significant contribution to the understanding of FGIDs and to patient care. To this end, methodological issues related to cross-cultural research and competences required for its conduct are presented together with a critique of published studies and recommendations for future research in the area. The term 'cross-cultural' research in FGIDs is usually applied to the results of prevalence studies, for example comparative studies of IBS prevalence in different countries and ethnic groups. The validity of these comparisons is impacted negatively by the lack of uniformity in research methods. In addition to prevalence studies, cross-cultural research can make a significant contribution in areas such as molecular biology, genetics, psychosocial factors, symptom presentation, extra-intestinal comorbidity, diagnosis and treatment, determinants of disease severity, healthcare utilization, and health-related quality of life, all issues that can be affected by culture, ethnicity and race. Well-designed and implemented cross-cultural studies can advance our knowledge in many FGID-related areas ranging from epidemiology through psychosocial factors, pathophysiological mechanisms and therapeutics. These studies, conducted by investigators with competence in cross-cultural research methodology, can advance our understanding of the FGIDs and contribute to improved patient care.

Psychosomatik der Darmerkrankungen/ Psychosomatic aspects of bowel diseases

Functional gastrointestinal disorders (FGID) and inflammatory bowel diseases (IBD) are the most frequently studied bowel disorders in the context of a bio psycho-social model. FGID are associated with significant work absenteeism, impaired quality of life, and increased medical costs. Many patients also suffer from psychosocial problems. Most of the research in FGID to date has focused on the irritable bowel syndrome. Randomised controlled studies have shown that psychotherapy is superior to conventional medical therapy. The gut-focussed hypnotherapy seems to be very successful. For IBD it is increasingly recognized that the psycho-neuro-endocrine network can modulate inflammation and pain perception and that psychosocial factors are related to exacerbation of and coping with IBD. The psychosocial consequences of the illness become more significant with increasing severity of the disease. Therefore integrated psychosomatic care should be provided, the patient's psychosocial status and the demand for additional psychological care should be assessed and offered, if indicated.

Brain research in functional gastrointestinal disorders.

The current understanding is that functional gastrointestinal disorders (FGIDs) result from dysregulation of the bidirectional communication between the gut and the brain (i.e., the brain-gut axis), modulated by various psychosocial and environmental factors (i.e., the biopsychosocial model). This concept has led to a growing interest in the research of brain function in relation to gut motor and sensory function. Brain research on the mechanisms that are involved in the generation of gastrointestinal symptoms includes studies of the gut response to brain stimulation with technique such as transcranial magnetic stimulation or studies of the brain response to gut stimulation by cortical evoked potentials, positron emission tomography, and functional magnetic resonance imaging. Studies using these techniques have shown that visceral/gut sensation involves activation of several brain regions that are associated with various brain functions, including sensation, cognition, and affect. The complexity of the brain response to visceral stimulation and the multidetermined nature of FGIDs make studies of brain function in FGID patients difficult and demands great caution in interpreting their results. Nevertheless, brain research in FGIDs is an emerging field and suggests that patients with irritable bowel syndrome differ from healthy subjects in the way that their brain response to visceral (e.g., rectal) distention. These studies emphasize the role of the central nervous system in conducting and processing visceral signals and suggest that alteration in brain processes involving perception and affective responses might be key factors in the pathogenesis of functional gastrointestinal symptoms.