Humans are the only known reservoir of H. pylori infection. How the organism is transmitted from one person to another, however, remains unknown. Data collected during the investigators initial funding period indicate that viable H. pylori are shed by infected hosts in vomitus and diarrheal stools under conditions that simulate gastroenteritis. In addition, H. pylori infection has been linked to increased risk for diarrheal disease, specifically, symptomatic cholera and infantile diarrhea. The investigators postulate that H. pylori decreases gastric acidity, allowing gastroenteritis pathogens to circumvent the first barrier to entry into the intestine. The gastroenteritis pathogens then cause diarrhea and vomiting, fostering excretion of H. pylori and completion of the transmission cycle. With this submission, they propose: 1) to determine whether H. pylori infection, by decreasing gastric acidity, is permissive of gastrointestinal infection with acid sensitive organisms. and 2) to determine whether gastrointestinal infection which leads to diarrhea and vomiting increases shedding of H. pylori.
These aims will be accomplished in a three-pronged fashion: First, they will identify suitable acid-resistant and acid-sensitive strains of non-pathogenic E. coli for human inoculation, and determine the conditions for recovering these organisms from stools. Next, they will administer the acid-resistant/acid-sensitive pair to human subjects and determine the effects of H. pylori infection and gastric acidity on bacterial survival. Last, they will inoculate H. pylori infected and uninfected human subjects with low doses of an acid-sensitive, enteropathogenic E. coli (EPEC) and determine both how H. pylori affects EPEC infectivity and how EPEC affects H. pylori shedding. H. pylori infection causes gastric cancer-the second leading cause of cancer death worldwide-and peptic ulcer disease. Diarrheal disease remains a leading killer of children in developing countries, causing 20 percent of infant mortality worldwide. In these same countries where diarrheal disease runs rampant, H. pylori infects up to 80 percent of the population. If a causal link between these diseases can be established, then treatment or prevention of H. pylori would attain a significantly higher public health priority than it currently occupies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK053689-06
Application #
6635089
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Program Officer
Hamilton, Frank A
Project Start
1997-09-30
Project End
2006-02-28
Budget Start
2003-03-01
Budget End
2004-02-29
Support Year
6
Fiscal Year
2003
Total Cost
$263,760
Indirect Cost
Name
Stanford University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Chang, Alicia Hsin-Ming; Haggerty, Thomas Dean; de Martel, Catherine et al. (2011) Effect of Helicobacter pylori infection on symptoms of gastroenteritis due to enteropathogenic Escherichia coli in adults. Dig Dis Sci 56:457-64
De Martel, Catherine; Ratanasopa, Sarah; Passaro, Douglas et al. (2006) Validation of the blood quininium resin test for assessing gastric hypochlorhydria. Dig Dis Sci 51:84-8
Weiner, Daniel E; Tighiouart, Hocine; Vlagopoulos, Panagiotis T et al. (2005) Effects of anemia and left ventricular hypertrophy on cardiovascular disease in patients with chronic kidney disease. J Am Soc Nephrol 16:1803-10
Weiner, Daniel E; Tighiouart, Hocine; Stark, Paul C et al. (2004) Kidney disease as a risk factor for recurrent cardiovascular disease and mortality. Am J Kidney Dis 44:198-206
Parsonnet, J; Shmuely, H; Haggerty, T (1999) Fecal and oral shedding of Helicobacter pylori from healthy infected adults. JAMA 282:2240-5