2015 AGA – Rome Foundation Research Award Recipient
Principle Investigator: Madhusudan Grover
Assistant Professor of Medicine
Mayo Clinic, Rochester, Minnesota
Madhu Grover, MBBS, studies mechanisms involved in the pathophysiology of irritable bowel syndrome (IBS), with a specific focus on the role of intestinal mucosal barrier function. Dr. Grover is particularly interested in studying the role of host and pathogen factors in the development of IBS and other functional gastrointestinal disorders following infectious gastroenteritis. Dr. Grover conducts research studies on patients with these disorders using a variety of complementary in vivo and ex vivo techniques. Dr. Grover is also developing and conducting clinical trials of newer therapeutic options for patients with IBS, functional dyspepsia and gastroparesis.
Title: Barrier function alterations in post-infectious irritable bowel syndrome
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.