Host Epithelial Responses in Pathophysiology of Campylobacter jejuni Post Infection Irritable Bowel Syndrome
Abstract
Intestinal infections, including with C. jejuni are common during military deployment. Epidemiological studies from military and civilian populations have shown that up to 1 in 6 suffering from a gastrointestinal infection may develop post-infection IBS (PI-IBS). This risk is even higher if there is comorbid psychological stress. This proposal integrates the use of colonoids derived from human volunteers who can be considered demographically at high-risk for PI-IBS development and the use of clinical C. jejuni isolates that have been known to cause PI-IBS. Over the last year, we have recruited 20 healthy volunteers (12 females, 8 males) between the ages of 18-35 years without or with the presence of chronic psychological stress. Sigmoid colonic biopsies were obtained to isolate intestinal crypts which were used to develop colonoids. These were infected with a set of clinical C. jejuni isolates and in vitro infectivity was studied. Interim analysis suggests that all colonoids get infected with C. jejuni but demonstrate differential virulence patterns (adhesion, invasion and barrier disruption). This suggests human colonoids can serve as a unique model for studying host interactions with C. jejuni. Transcriptomic and proteomic studies will be performed next on the infected colonoids to determine molecular changes induced by the infection. These will be compared between colonoids obtained from males and females and those without and with psychological stress. Overall, these studies will identify the influence of host characteristics upon interaction with the microbe and the epithelial responses elicited. These will help identify the role of acute infection in subsequent development of post-infection irritable bowel syndrome.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2019
- Accession Number
- AD1094496
Entities
People
- Madhusudan Grover