Phenotyping of subjects for large scale studies on patients with IBS

Abstract

• Irritable bowel syndrome (IBS) is a complex condition with multiple factors contributing to its etiology and pathophysiology, resulting to date in no specific reliable biomarker being identified.• Large multi-center pan European/World studies carefully phenotyping and characterizing patients may help identify subpopulations with accuracy and consistency, aiding future research and treatment.• This position paper highlights the necessary requirements to standardize the process of selecting and phenotyping IBS patients and how to organize the collection and storage of patient information/samples in such studies. AbstractBackground Irritable bowel syndrome (IBS) is a complex condition with multiple factors contributing to its aetiology and pathophysiology. Aetiologically these include genetics, life-time events and environment, and physiologically, changes in motility, central processing, visceral sensitivity, immunity, epithelial permeability and gastrointestinal microflora. Such complexity means there is currently no specific reliable biomarker for IBS, and thus IBS continues to be diagnosed and classified according to symptom based criteria, the Rome Criteria. Carefully phenotyping and characterisation of a 'large' pool of IBS patients across Europe and even the world however, might help identify sub-populations with accuracy and consistency. This will not only aid future research but improve tailoring of treatment and health care of IBS patients. Purpose The aim of this position paper is to discuss the requirements necessary to standardize the process of selecting and phenotyping IBS patients and how to organise the collection and storage of patient information/samples in such a large multi-centre pan European/global study. We include information on general demographics, gastrointestinal symptom assessment, psychological factors, quality of life, physiological evaluation, genetic/epigenetic and microbiota analysis, biopsy/ blood sampling, together with discussion on the organisational, ethical and language issues associated with implementing such a study. The proposed approach and documents selected to be used in such a study was the result of a thoughtful and thorough four-year dialogue amongst experts associated with the European COST action BM1106 GENIEUR (www.GENIEUR.eu).

Systemic cytokines are elevated in a subset of patients with irritable bowel syndrome but largely unrelated to symptom characteristics

“…22,23 Moreover, associations between serum levels of cytokines, eg, IL-6 and symptoms such as abdominal pain and discomfort have been demonstrated, 24,25 but many studies require further validation and/or are performed on small IBS cohorts which may not encompass the full spectrum of patients. 7 In a recent study by our group, IBS patients and HS could not be discriminated from each other through multivariate statistical analysis based upon their cytokine profiles; however, we detected an "immuno-active" subset of patients particularly defined by elevated serum cytokine levels of IL-6 and IL-8. 16 In that study, only modest associations between levels of pro-inflammatory cytokines and symptoms, and pathophysiology were detected.…”

“…Approximately 5%‐15% of adults in the western world are afflicted with this combination of gastrointestinal (GI) symptoms and are diagnosed with IBS . Irritable bowel syndrome patients have a recognized heterogeneity and differ in aspects such as severity and constellation of symptoms, abruptness of onset and possible triggers, making effective subgrouping a challenging but necessary task …”

“…However, pro‐inflammatory IL‐1β, IL‐6, IL‐8, tumor necrosis factor‐alpha (TNF), and anti‐inflammatory IL‐10, important cytokines in the immune system are commonly reported as being significantly altered in IBS patients compared to healthy subjects (HS) . Moreover, associations between serum levels of cytokines, eg, IL‐6 and symptoms such as abdominal pain and discomfort have been demonstrated, but many studies require further validation and/or are performed on small IBS cohorts which may not encompass the full spectrum of patients . In a recent study by our group, IBS patients and HS could not be discriminated from each other through multivariate statistical analysis based upon their cytokine profiles; however, we detected an “immuno‐active” subset of patients particularly defined by elevated serum cytokine levels of IL‐6 and IL‐8 .…”

“…[3][4][5] Irritable bowel syndrome patients have a recognized heterogeneity and differ in aspects such as severity and constellation of symptoms, abruptness of onset and possible triggers, 6 making effective subgrouping a challenging but necessary task. 7 The well-established clinical practice of subtyping according to predominant bowel habit, ie, constipation (IBS-C), diarrhea (IBS-D), or mixed (IBS-M), is both tangible and non-invasive. However, the apparent fluctuation in stool consistency of an individual makes subtyping difficult.…”

Heart rate variability characteristics of patients with irritable bowel syndrome and associations with symptoms

“…Validated self-report questionnaires were used to measure symptom pattern and severity in the IBS patients. 36 In addition to the questionnaires described below, the patients were also asked to register every bowel movement over a 2-week period in a diary and characterize the stool frequency and consistency of each bowel movement by use of the Bristol Stool Form scale. 37 This scale determines the stool form in categories ranging from 1 (hard, lumpy stools) to 7 (loose, watery stools).…”