Gut microbiome and diet may be important in irritable bowel syndrome (IBS), inflammatory bowel disease (IBD) and comorbid psychiatric conditions, but the mechanisms are unclear. We will create a ...large cohort of patients with IBS, IBD and healthy controls, and follow them over time, collecting dietary and mental health information and biological samples, to assess their gastrointestinal (GI) and psychological symptoms in association with their diet, gut microbiome and metabolome.
This 5-year observational prospective cohort study is recruiting 8000 participants from 15 Canadian centres. Persons with IBS who are 13 years of age and older or IBD ≥5 years will be recruited. Healthy controls will be recruited from the general public and from friends or relatives of those with IBD or IBS who do not have GI symptoms. Participants answer surveys and provide blood, urine and stool samples annually. Surveys assess disease activity, quality of life, physical pain, lifestyle factors, psychological status and diet. The main outcomes evaluated will be the association between the diet, inflammatory, genetic, microbiome and metabolomic profiles in those with IBD and IBS compared with healthy controls using multivariate logistic regression. We will also compare these profiles in those with active versus quiescent disease and those with and without psychological comorbidity.
Approval has been obtained from the institutional review boards of all centres taking part in the study. We will develop evidence-based knowledge translation initiatives for patients, clinicians and policymakers to disseminate results to relevant stakeholders.
NCT03131414.
This study examined the role of outward K(+) currents in the acinar cells underlying secretion from Brunner's glands in guinea pig duodenum. Intracellular recordings were made from single acinar ...cells in intact acini in in vitro submucosal preparations, and videomicroscopy was employed in the same preparation to correlate these measures with secretion. Mean resting membrane potential was -74 mV and was depolarized by high external K(+) (20 mM) and the K(+) channel blockers 4-aminopyridine (4-AP), quinine, and clotrimazole. The cholinergic agonist carbachol (60-2,000 nM; EC(50) = 200 nM) caused a concentration-dependent initial hyperpolarization of the membrane and an associated decrease in input resistance. This hyperpolarization was significantly decreased by 20 mM external K(+) or membrane hyperpolarization and increased by 1 mM external K(+) or membrane depolarization. It was blocked by the K(+) channel blockers tetraethylammonium (TEA), 4-AP, quinine, and clotrimazole but not iberiotoxin. When videomicroscopy was employed to measure dilation of acinar lumen in the same preparation, carbachol-evoked dilations were altered in a parallel fashion when external K(+) was altered. The dilations were also blocked by the K(+) channel blockers TEA, 4-AP, quinine, and clotrimazole but not iberiotoxin. These findings suggest that activation of outward K(+) currents is fundamental to the initiation of secretion from these glands, consistent with the model of K(+) efflux from the basolateral membrane providing the driving force for secretion. The pharmacological profile suggests that these K(+) channels belong to the intermediate conductance group.
The Rome IV Diagnostic Questionnaires were developed to screen for functional gastrointestinal disorders (FGIDs), serve as inclusion criteria in clinical trials, and support epidemiological surveys. ...Separate questionnaires were developed for adults, children/adolescents, and infants/toddlers. For the adult questionnaire, we first surveyed 1,162 adults without gastrointestinal disorders, and recommended the 90
percentile symptom frequency as the threshold for defining what is abnormal. Diagnostic questions were formulated and verified with clinical experts using a recursive process. The diagnostic sensitivity of the questionnaire was tested in 843 patients from 9 gastroenterology clinics, with a focus on clinical diagnoses of irritable bowel syndrome (IBS), functional constipation (FC), and functional dyspepsia (FD). Sensitivity was 62.7% for IBS, 54.7% for FD, and 32.2% for FC. Specificity, assessed in a population sample of 5,931 adults, was 97.1% for IBS, 93.3% for FD, and 93.6% for FC. Excess overlap among IBS, FC, and FD was a major contributor to reduced diagnostic sensitivity, and when overlap of IBS with FC was permitted, sensitivity for FC diagnosis increased to 73.2%. All questions were understandable to at least 90% of individuals, and Rome IV diagnoses were reproducible in ¾ of patients after one month. Validation of the pediatric questionnaires is ongoing.
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