Campylobacter Jejuni Enteritis in Development of Irritable Bowel Syndrome (IBS)

Dr. Grover's Gastrointestinal Barrier Function Lab studies how changes in the epithelial barrier function and gut microbiota play a role in development of IBS after infection with C. jejuni. The lab is also studying interactions between C. jejuni and host physiology.

The lab's research goals are to obtain mechanistic information on the pathophysiology of postinfectious IBS (PI-IBS), lay the foundation for identifying people at risk of PI-IBS, and drive development of interventions aimed at decreasing the incidence of PI-IBS.

Over the last decade, a significant number of epidemiological studies have validated the entity of PI-IBS. The de novo onset of IBS after common gastrointestinal infections provides researchers with opportunities to study mechanisms that can be generalizable to IBS. Dr. Grover's team collaborates with the Minnesota Department of Health to recruit people with positive C. jejuni cultures from the community, avoiding tertiary referral bias.

Developing Biomarkers for Measurement of Intestinal Permeability

The lab is developing novel in vivo and ex vivo biomarkers for measurement of mucosal barrier function. Dr. Grover's research team is also expanding upon ex vivo measurement techniques of barrier function on endoscopically obtained human biopsies. The goal is to use functional studies of mucosal barrier and secretion in individualizing pathophysiological mechanisms and implementing treatment strategies unique to the involved mechanisms.

Assays based on urinary excretion of poorly absorbable carbohydrates are frequently used in the measurement of intestinal permeability. The Gastrointestinal Barrier Function Lab has shown that 13C mannitol offers a better molecule than the standard 12C mannitol for in vivo measurement of intestinal permeability; the lab is now conducting further studies to validate this finding. These include determining responsiveness to NSAID-induced perturbation of small intestinal permeability and understanding changes in diseased states such as irritable bowel syndrome with constipation (IBS-C) and PI-IBS.

Molecular and Cellular Mechanisms in Gastroparesis

The National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium was established to understand the pathophysiology of gastroparesis to investigate novel treatments for this condition. Gianrico Farrugia, M.D., is the principal investigator for the consortium's histology core at Mayo Clinic, and Dr. Grover serves as co-investigator.

Over the last several years, researchers in the consortium have significantly increased the understanding of cellular and molecular changes in diabetic and idiopathic gastroparesis. Our findings have led to the evolution of the mechanistic paradigm that now involves an interaction between the immune cells (macrophages) and interstitial cells of Cajal (ICC) to play a key role in pathophysiology of gastroparesis.

We have a repository of full-thickness gastric tissue from well-phenotyped gastroparesis patients recruited across the clinical sites of the gastroparesis consortium. These will be used for future mechanistic studies to enhance the understanding of the pathophysiology of human gastroparesis, which will ultimately provide novel targets for drug development.

Dyspepsia and IBS Clinical Trials

The Gastrointestinal Barrier Function Lab is routinely engaged in clinical trials for functional dyspepsia and irritable bowel syndrome, with an emphasis on conducting pharmacodynamics and pharmacokinetic studies for novel treatment targets.

The lab has developed assays to measure gastrointestinal transit, sensation and permeability at the Mayo Clinic Center for Clinical and Translational Science Clinical Research and Trials Unit. These assays allow the team to perform deep physiological phenotyping of patients with functional gastrointestinal disorders that's used for selection of eligible patients and outcome assessment in clinical trials.

In addition, the lab works with the genomics core of the Mayo Clinic Center for Individualized Medicine for next-generation DNA and RNA sequencing.