Basic Science Research

Basic science research in the MUSC Digestive Disease Center focuses on pathophysiology of the Gram-negative bacterium Helicobacter pylori. This organism colonizes the surface of the mucosa in the highly acidic environment of the stomach and is one of the most successful known pathogens. H. pylori infects about 50% of the world population, causing chronic gastritis in all infected humans and more severe gastric diseases in 10-15% of infected individuals. Infections with H. pylori commonly occur in early childhood and may persist throughout the lifetime of the host.

Genetic studies have also revealed that H. pylori has coexisted with humans at least since early human migrations out of Africa ~58,000 years ago. Because of the lengthy co-existence of H. pylori with humans, bacterial colonization has been hypothesised to have been beneficial, providing a selective advantage for humans. In the 21st century, however, H. pylori infections are responsible for high rates of morbidity and mortality as a consequence of peptic ulcer disease, mucosa-associated lymphoid tissue (MALT) lymphoma and gastric adenocarcinoma. The risk of gastric adenocarcinoma is high in infected patients with non-ulcer dyspepsia or gastric ulceration who suffer from severe gastric atrophy and intestinal metaplasia. Gastric adenocarcinoma represents the second leading cause of cancer-associated death worldwide with ~700,000 people dying every year.

Colonization of the gastric mucosa by H. pylori causes diffuse acute and later chronic inflammation whose severity and pathological sequelae are determined by bacterial virulence factors and host genetic factors. A primary goal of gastric physiology is to regulate and sustain acid secretion at levels sufficient to sterilize ingested nutrients, but in a setting of mucosal inflammation, this function is inevitably impaired. In the case of chronic persistent infection, the degree of impairment, and whether acid secretory capacity is increased or decreased, depends on the anatomical focus of the infection. Thus, H. pylori-induced chronic gastritis may follow an antrum-predominant or corpus-predominant phenotype, the former being associated with gastrin-driven acid hypersecretion and the latter with acidhyposecretion driven by H. pylori inhibition of H,K-ATPase, cytokines derived from inflammatory infiltrates, and other mechanisms.

Dr. Adam Smolka's research group in the MUSC DDC studies the molecular mechanisms underlying acute H. pylori-induced hypochlorydria, in order to elucidate bacterial strategies to overcome a stringent barrier to gastric colonization, and to identify key cell signaling elements targeting the acid secretory process that are subject to endogenous and exogenous control.