? This career development application has two components: I. A mentored research project, and II. Educational/training activities. Epidemiological studies have implicated intestinal inflammation and chronic activation of the immune system in the etiology of IBS for some patients. Recent research in animal models suggests that these factors can be involved in the pathophysiological mechanisms responsible for intestinal dysmotility and visceral hypersensitivity. However, the role of intestinal inflammation and mucosal immune activation has not been adequately and systematically investigated in patients with IBS. In the proposed research project we will compare sub-clinical mucosal inflammation between patients with diarrhea predominant IBS (D-IBS) and control. We will specifically look at pro- and anti-inflammatory cytokines and inflammatory-associated neuropeptides. Analyses will be performed by Real-time PCR and ELISA techniques to verify results. In our second aim we will investigate whether alterations in inflammatory markers are associated with alterations with relevant intestinal physiology including colonic pain thresholds, phasic motility, and smooth muscle tone. We will study 33 IBS patients with D-IBS and 33 healthy controls. Intestinal physiological data will be collected on the same study population of an NIH supported study on the heterogeneity of IBS (NIDDK Grant DK 31369, Whitehead PI) on which Dr. Whitehead is collaborating with Dr. Ringel. The educational/training components of this proposal have been developed with the advice of Dr. Ringel's mentors: Dr. Balfour Sartor is a world renowned expert and researcher in intestinal inflammation and Dr. William Whitehead is a world renowned expert and researcher in functional Gl disorders. We propose formal coursework as well as laboratory training aiming to expand and increase Dr. Ringel's knowledge and skills in theories and research methodologies in these areas. The overall goal is to establish Dr. Ringel as an independently-funded translational researcher. Thus, the methodologies, results and protocols that will be developed during the award will be used to design mechanistic intervention studies and as preliminary data for submission of future (NIH) grants. ? ?

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Mentored Patient-Oriented Research Career Development Award (K23)
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Study Section
Special Emphasis Panel (ZDK1-GRB-8 (M2))
Program Officer
Podskalny, Judith M,
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University of North Carolina Chapel Hill
Internal Medicine/Medicine
Schools of Medicine
Chapel Hill
United States
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Hod, Keren; Ringel-Kulka, Tamar; Martin, Christopher F et al. (2016) High-sensitive C-Reactive Protein as a Marker for Inflammation in Irritable Bowel Syndrome. J Clin Gastroenterol 50:227-32
Ringel-Kulka, Tamar; Benson, Andrew K; Carroll, Ian M et al. (2016) Molecular characterization of the intestinal microbiota in patients with and without abdominal bloating. Am J Physiol Gastrointest Liver Physiol 310:G417-26
Ringel-Kulka, Tamar; Choi, Chang Hwan; Temas, Daniel et al. (2015) Altered Colonic Bacterial Fermentation as a Potential Pathophysiological Factor in Irritable Bowel Syndrome. Am J Gastroenterol 110:1339-46
Ringel, Yehuda; Maharshak, Nitsan; Ringel-Kulka, Tamar et al. (2015) High throughput sequencing reveals distinct microbial populations within the mucosal and luminal niches in healthy individuals. Gut Microbes 6:173-81
Ringel-Kulka, T; Goldsmith, J R; Carroll, I M et al. (2014) Lactobacillus acidophilus NCFM affects colonic mucosal opioid receptor expression in patients with functional abdominal pain - a randomised clinical study. Aliment Pharmacol Ther 40:200-7
Ringel-Kulka, Tamar; Cheng, Jing; Ringel, Yehuda et al. (2013) Intestinal microbiota in healthy U.S. young children and adults--a high throughput microarray analysis. PLoS One 8:e64315
Ringel, Yehuda; Maharshak, Nitsan (2013) Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol 305:G529-41
Carroll, Ian M; Ringel-Kulka, Tamar; Ferrier, Laurent et al. (2013) Fecal protease activity is associated with compositional alterations in the intestinal microbiota. PLoS One 8:e78017
Carroll, I M; Ringel-Kulka, T; Siddle, J P et al. (2012) Alterations in composition and diversity of the intestinal microbiota in patients with diarrhea-predominant irritable bowel syndrome. Neurogastroenterol Motil 24:521-30, e248
Carroll, Ian M; Ringel-Kulka, Tamar; Keku, Temitope O et al. (2011) Molecular analysis of the luminal- and mucosal-associated intestinal microbiota in diarrhea-predominant irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol 301:G799-807

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