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| Microbiome and pain in irritable bowel syndrome (IBS) | |
|---|---|
| Investigator (PI): | Heitkemper, Margaret McLean; Shulman, Robert |
| Performing Organization (PO): |
(Current): University of Washington, School of Nursing / (206) 543-8736 |
| Supporting Agency (SA): | National Institutes of Health (NIH), National Institute of Nursing Research (NINR) || National Institutes of Health (NIH), Office of the Director (OD) |
| Initial Year: | 2014 |
| Final Year: | 2018 |
| Record Source/Award ID: | RePorter/R01NR014479 |
| Funding: | 2014 Award Amount: $394,782 2015 Award Amount: $369,204 2016 Award Amount: $480,581 2017 Award Amount: $569,033 |
| Award Type: | Grant |
| Award Information: | Reports resulting from this project |
| Abstract: | Approximately 10-20% of adults experience chronic abdominal symptoms (abdominal pain/discomfort and associated bowel changes [constipation and/or diarrhea]) compatible with a diagnosis of irritable bowel syndrome (IBS). In the US as well as other western countries, women seek health care services disproportionately to men. IBS is defined as chronic abdominal pain/discomfort accompanied by altered bowel pattern (diarrhea, constipation, or both [mixed]). The public health impact of IBS in the US is enormous with direct and indirect costs totaling approximately $6 billion/year. Studies suggest an interplay between increased gastrointestinal (GI) permeability ("leaky gut"), abnormalities in the composition of the GI microbiome (defined as bacteria, their genomes, and interaction with the host), altered immune responses, autonomic dysfunction (high sympathetic tone), and psychosocial distress lead to the symptoms and the subsequent functional impact of IBS. Our long-term goal is to delineate the contribution of pathobiology and psychosocial distress to better inform patient management (e.g., diet versus cognitive behavioral approaches). We propose to compare GI microbiota, intestinal permeability, cytokines, and GI and psychological distress symptoms in menstruating women with IBS and without IBS. We also will derive important information about women with IBS with no evidence of abnormal GI markers. The current proposal will also allow us to define microbiome composition and pathophysiological features tied to symptoms, and likely etiology. Thus, the first specific aim is to compare GI microbiome, permeability, and cytokines in women (18-45 years of age) with IBS (n=100) vs. healthy controls (HC) (n=50) without IBS. Based on pediatric data, we hypothesize that among women with IBS, those with a GI microbiome enriched with Proteobacteria/Enterobacteriaceae, increased GI permeability or increased cytokine levels will have greater abdominal pain symptoms versus those without this Proteobacteria/Enterobacteriaceae-enriched microbiota composition, normal permeability, or lower cytokine levels. The second aim will be to compare abdominal pain, other IBS symptoms and psychosocial distress symptoms in those IBS subjects with abnormal versus normal GI biomarkers. In addition, we will explore patterns of associations among GI biomarkers, and of GI biomarkers with abdominal pain and other symptoms. The goal is to identify possible IBS subgroups based on biomarkers. This research is innovative because we will use biomarkers (e.g., GI microbiome analyses, permeability, and serum markers) applied novelty to characterize pathobiologically what heretofore has been primarily a phenotypically and arbitrarily defined condition. We will integrate psychosocial factors (e.g., anxiety, somatization, co-morbid functional conditions) that our preliminary data suggest are likely to predominate in some women with IBS. |
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| Country: | United States |
| State: | Washington |
| Zip Code: | 98195 |
| UI: | 20174222 |
| Project Status: | Completed |
| Record History: | ('In 2016, NINR provided $380,581 and OD provided $100,000 in funding. NINR provided total funding for 2014, 2015, and 2017.',) |