The pathophysiology of irritable bowel syndrome (IBS) is poorly understood. Epidemology [sic] and physiological studies have suggested a possible role for the intestinal microbiota in the pathophysiology of the disorder. In addition, since IBS is a heterogenous [sic] disorder it is possible that there may be different etiological factors for the different subtypes of this condition;diarrhea-predominant IBS (D-IBS), constipation-predominant IBS (C- IBS), mixed bowel habit IBS (M-IBS). To date, the understanding of the contribution of the intestinal microbiota to the altered intestinal physiology and functional symptoms and the data regarding differences in the intestinal microbiota between the different subtypes of IBS and healthy controls are limited. Our hypothesis for this R03 grant is that the gut microbiota of patients with certain subtypes of IBS is distinct from that of healthy controls. The proposed research project will use a novel approach combining three molecular biology techniques including Terminal-Restriction Fragment Length Polymorphism (T-RFLP) fingerprinting, pyro-sequencing and quantitative polymerase chain reaction (qPCR) to compare the fecal microbiota between patients with different subtypes of IBS and healthy controls. We will study 20 patients from each IBS subgroup and 20 controls. The results of this study will be used as preliminary data for future, in depth, investigations regarding the role of the intestinal microbiota in IBS. If our hypotheses are confirmed, it will provide new insight to the understanding of the disorder and may lead to new mechanistic investigations and hypothesis driven treatments for functional GI disorders by targeting the intestinal flora. The protocols and the results from this study will also provide the basis for future (NIH) grant submissions to further investigate the role of intestinal bacteria in these disorders.

Public Health Relevance

Irritable Bowel Syndrome (IBS) is a gastrointestinal disorder of unknown cause and can occur as diarrhea, constipation or mixed bowel habit IBS (D-IBS, C-IBS and M-IBS). Recent studies point to an association of the bacteria in our intestine (the intestinal microbiota) with this disorder. The hypothesis of this study is that the intestinal microbiota of patients experiencing D-IBS, C-IBS or M-IBS is different to the microbiota of healthy people. This study will use advanced molecular techniques to analyze the gut microbiota in patients experiencing different subtypes of IBS and healthy people. This study will investigate the role of the intestinal microbiota in IBS. Additionally, this study will provide insight to the understanding of IBS and my lead to new treatments for functional gastrointestinal disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Small Research Grants (R03)
Project #
5R03DK084294-02
Application #
8072701
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Podskalny, Judith M,
Project Start
2010-05-17
Project End
2012-04-30
Budget Start
2011-05-01
Budget End
2012-04-30
Support Year
2
Fiscal Year
2011
Total Cost
$73,260
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
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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, 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, 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