Background: Irritable bowel syndrome (IBS) affects 15% of the U.S. population accounting for an estimated $20 billion in health care costs annually. 4-36% of those suffering from infectious enteritis may develop post-infectious IBS (PI-IBS). Campylobacter jejuni is a leading cause of bacterial enteritis in the U.S. and a reportable illness to public health departments. Our preliminary data suggests that PI-IBS is common (22%) following C. jejuni enteritis and colonic mucosal barrier function in vivo and ex vivo is impaired in PI-IBS. Additionally, C. jejuni strains that lead to PI-IBS are genetically different from the control strains and cause greater disruption of in vitro barrier function. My overall hypothesis is that C. jejuni leads to PI-IBS by causing strain-dependent alteration in barrier function involving myosin light chain phosphorylation. I will test this hypothesis in 2 specific aims. I will identify laboratory-confirmed C. jejuni enteritis cases through a collaboration with the Minnesota Department of Health.

Aims: In aim 1, I will assess the structure and function of the colonic epithelial barrier in acute C. jejunienteritis patients and follow these patients at 6 months to ascertain PI-IBS development. I expect to show that the degree of barrier disruption during acute enteritis predicts development of PI-IBS. In aim 2, I will study differences in the presence of virulence genes among PI-IBS and control C. jejuni strains and study their effects on in vitro barrier function, especially delineating the role of myosin light chain phosphorylation in this process. I expect to show that C. jejuni strains that led to PI-IBS express specific virulence genes and cause greater disruption of in vitro barrier function. This proposal will uniquely allow studying the mechanisms for PI-IBS development following confirmed C. jejuni infection in samples derived from the U.S. communities using integrative in vivo and ex vivo techniques with the aim of identifying “high-risk” enteritis cases for PI-IBS development and developing strategies for future interventions to prevent or treat PI-IBS.