PROJECT SUMMARY Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction affecting about 11% of the global population and ~ 10-20% of adults in Western countries, and highly prevalent in children, impairing social development and quality of life (QoL). Abdominal pain, bloating, constipation and/or diarrhea are characteristic symptoms of IBS, often associated with food intake. Disease mechanisms include increased pain sensation from visceral nerves (hypersensitivity), altered bowel motility, and alterations in the gut microbiota. Treatments are limited and often do not completely relieve pain. Identifying factors involved in IBS pathophysiology as potential therapeutic targets is essential. Bowel motility may play a critical role in IBS pathophysiology, but its role relative to dietary triggers is unknown. Current diagnostic methods have limited ability to address spontaneous symptoms during daily life. Diagnoses solely based on symptoms are non-specific and may lead to suboptimal therapies. We use a new non-invasive diagnostic Wireless Patch System (WPS) to simultaneously evaluate real-time gastric, small intestine, and colonic myoelectric signals as a measure of organ motor activity over a 7-day period alongside symptoms and dietary intake. Up to 90% of patients with IBS report symptoms related to food intake. Specifically, food rich in fermentable, oligosaccharide, disaccharide, monosaccharide, and polyols (FODMAP) can exacerbate IBS symptoms. Low-FODMAP diets can improve symptoms and quality of life, however, poor adherence is common resulting in failure to fully resolve symptoms, and when imbalanced, can adversely impact overall nutrition. Identifying individual symptom triggering foods (FODMAPs and others) and their effect on bowel motility could improve adherence and care. This prospective, longitudinal, observational study of children with IBS and unaffected controls will simultaneously collect bowel activity, diet, GI symptoms, and psychosocial health data and evaluate contributions to IBS symptoms in real-time. In Aim 1 we simultaneously assess gastric, small bowel, and colonic motility in children with IBS and controls using the non-invasive WPS. We hypothesize bowel activity will differ between IBS and controls, and between IBS-C, IBS-D, and controls; and between symptomatic and asymptomatic periods. In Aim 2 we evaluate the effect of diet on bowel motility and symptoms in children with IBS and controls. We hypothesize that high intake of FODMAP foods and other known dietary triggers will associate with distinct patters of bowel activity, and symptom severity in children with IBS but not in controls. We further hypothesize that stress and anxiety exacerbate the association between diet, motility, and symptom severity. Our innovative approach employs a non-invasive measure of bowel activity, and deep phenotyping of dietary intake and symptoms under free-living conditions to elucidate the relationship between diet, bowel motility, and IBS symptoms, addressing several knowledge gaps in our understanding of mechanisms driving IBS symptoms. This study will provide the foundation for larger trials testing how motility and diet assessment are essential in developing personalized therapies for children with IBS.

PROJECT NARRATIVE Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction characterized by abdominal pain, distension, or bloating, and altered defecation patterns in which treatments are limited and often do not completely relieve symptoms. This proposal seeks to simultaneously evaluate gastric, small bowel, and colonic motility using a non- invasive wireless patch system, dietary intake, and psychosocial health in children with IBS compared to controls to determine if bowel motility and diet collectively contribute to IBS symptoms. This approach will advance our understanding of IBS pathophysiology by identifying specific symptom triggers, and serve as foundation for larger trials testing the utility of bowel motility and diet assessment in the development of personalized therapies in IBS.