Diverticulosis is a common and expensive condition in the United States. In 2004 there were 815,000 hospitalizations for diverticular disease, 3.3 million ambulatory care visits, and 2.4 million prescriptions written. With an aging population all these figures will increase. Despite the considerable economic and medical burden from diverticular disease, information on the etiology is largely nonexistent because asymptomatic diverticulosis has never been adequately studied. The proposed study builds upon a cross sectional study in which, contrary to expectation, the investigators found that a high-fiber diet was associated with increased (rather than a decreased) prevalence odds of diverticulosis with a significant dose response and a stronger effect among individuals with more frequent diverticula. The study will test the hypothesis that gut microbes are responsible for an altered immune response and a state of chronic inflammation that could lead to the development of diverticulosis possibly through alterations in the integrity of the colonic wall or altered motilit.
The aims of the study are: (1) To describe the prevalence and demographic characteristics of asymptomatic diverticulosis among a group of individuals undergoing first time screening colonoscopy. (2) To determine dietary and lifestyle risk factors for diverticulosis. (3) To evaluat the association between the adherent microbial flora and diverticulosis. (4) To assess local inflammation and immune activation in the colonic mucosa to support an inflammatory etiology for diverticulosis. To conduct the study, detailed dietary and lifestyle information will be colleced on 900 study subjects who undergo complete screening colonoscopy with careful investigation for diverticulosis. Sigmoid colon biopsies will be used to evaluate adherent bacterial organisms using pyrosequencing. Local inflammation and immune activation in tissue will be measured by immunohistochemistry. Blood will be stored for future studies of genes that might predispose to diverticular disease. The study is designed to correct the shortcomings of prior research on asymptomatic diverticulosis and test biological hypotheses about etiology. The proposed study is a first step in understanding the cause of diverticulosis with the hope of preventing the disease and its complications

Public Health Relevance

The goal of this project is to describe the prevalence and demographic characteristics of asymptomatic diverticulosis among a group of individuals undergoing first-time screening colonoscopy. The findings from this study will provide important insights into the role of diet, the gut microbiota and inflammation in the development of diverticulosis. The study could lead to eventual interventions to lower the prevalence of disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK094738-03
Application #
8640176
Study Section
Kidney, Nutrition, Obesity and Diabetes (KNOD)
Program Officer
Serrano, Jose
Project Start
2012-04-01
Project End
2016-03-31
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
3
Fiscal Year
2014
Total Cost
$548,439
Indirect Cost
$158,429
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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Peery, Anne F; Keku, Tope O; Martin, Christopher F et al. (2016) Distribution and Characteristics of Colonic Diverticula in a United States Screening Population. Clin Gastroenterol Hepatol 14:980-985.e1
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Mack, Christina DeFilippo; Brookhart, M Alan; Glynn, Robert J et al. (2015) Comparative Effectiveness of Oxaliplatin Versus 5-flourouricil in Older Adults: An Instrumental Variable Analysis. Epidemiology 26:690-9
Peery, Anne F; Sandler, Robert S; Ahnen, Dennis J et al. (2013) Constipation and a low-fiber diet are not associated with diverticulosis. Clin Gastroenterol Hepatol 11:1622-7
Peery, Anne F; Sandler, Robert S (2013) Diverticular disease: reconsidering conventional wisdom. Clin Gastroenterol Hepatol 11:1532-7
Mack, Christina DeFilippo; Glynn, Robert J; Brookhart, M Alan et al. (2013) Calendar time-specific propensity scores and comparative effectiveness research for stage III colon cancer chemotherapy. Pharmacoepidemiol Drug Saf 22:810-8
Peery, Anne F; Barrett, Patrick R; Park, Doyun et al. (2012) A high-fiber diet does not protect against asymptomatic diverticulosis. Gastroenterology 142:266-72.e1