Epidemiology and Pathophysiology of Post-Infectious Functional GI Disorders
Condition: Campylobacter Infections; Irritable Bowel Syndrome
MeSH terms: Campylobacter Infections; Irritable Bowel Syndrome
Study type: Observational

Summary: 
      Some people develop chronic abdominal pain with diarrhea or constipation after an episode of
      acute bacterial gastroenteritis. These symptoms can be consistent with post-infectious
      irritable bowel syndrome (IBS) and can last long after the acute infection is over. The exact
      reason why certain individuals develop these symptoms whereas others don't is not exactly
      clear.

      The researchers are studying changes in gastrointestinal permeability (movement of contents
      across the lining of the intestine) and transit (movement of food through the
      gastrointestinal tract). The researchers are also studying if there are any genetic risk
      factors that are associated with development of this disorder.
    

Detailed description: 
      The Centers for Disease Control and prevention (CDC) estimates that each year roughly 1 in 6
      Americans (or 48 million people) contact food-borne illnesses. The CDC also estimates that
      between 20 and 40% of individuals traveling to a developing country get traveler's diarrhea.
      There is morbidity from these illnesses, even after the acute episode is over. Thus, up to a
      third of patients suffering from acute infectious gastroenteritis (IGE), most often resulting
      from a food-borne outbreak or travel develop chronic gastrointestinal (GI) illnesses such as
      irritable bowel syndrome (IBS). In addition, recent studies are suggesting that military
      personnel who suffered from IGE during deployment are more likely to suffer from IBS
      post-deployment. This disorder has been described as post-infectious IBS (PI-IBS).

      Individuals with PI-IBS suffer from recurrent, debilitating abdominal pain and altered bowel
      function (diarrhea and/or constipation) and symptoms can be present for over 8 years after
      the acute IGE episode is over. It is estimated that up to 15% of the United States population
      suffers from IBS. This disorder creates significant impact on patient's daily functioning,
      overall quality of life and causes loss of work productivity. Despite the impact of this
      illness, treatment options for IBS have limited success, with a significant unmet need. Lack
      of understanding of underlying pathophysiological mechanisms has hampered development of
      effective treatment. More studies are required to enhance understanding of this disorder.
      Development of PI-IBS after an episode of acute IGE serves as a unique model to study
      risk-factors and mechanisms underlying PI-IBS and IBS in general. The researchers propose to
      study the epidemiological risk factors and pathophysiological mechanisms involved in the
      development of IBS among individuals suffering from episodes of acute IGE in the community.

      Pathophysiology of IBS includes abnormalities of GI motility, sensation, mucosal defense,
      immune function and psychosocial factors. The researchers propose to investigate overall risk
      and patient demographic, pathogen and illness related characteristics as predictors for
      development of PI-IBS among patients who had suffered from acute IGE. In addition, the
      researchers want to determine pathophysiological mechanisms leading to the development of
      this disorder.

      In order to achieve these goals, the researchers propose to establish collaboration with the
      Minnesota Department of Health (MDH) which conducts active surveillance for bacterial and
      parasitic cases of acute IGE and other reportable illnesses in Minnesota, as part of the
      mandate to detecting outbreaks and prioritize control efforts. We plan to establish
      retrospective and prospective cohorts in this proposal. A randomly selected sub-set of these
      patients will be invited to Mayo Clinic for detailed investigations including assessment of
      GI motility, permeability, endoscopic examination for colon biopsies, and diverse blood and
      stool assays using techniques that are all validated to provide information about the
      mechanism of PI-IBS. The researchers will also investigate variations in the barrier function
      pathway genes in tissues of PI-IBS patients and to understand the contribution of these
      genetic variations in immune activation and control of barrier function to increased
      susceptibility to PI-IBS.
    

Intervention name(s): DNA Analysis of Blood Sample; Flexible sigmoidoscopy with colonic biopsies; Small bowel and colonic gastrointestinal permeability; Stool sample analysis
Intervention type(s): Genetic; Procedure; Procedure; Diagnostic Test
Intervention description(s): DNA analysis of the genes possibly involved in IBS.; Endoscopy of the subject's lower colon in which biopsies of the lining of the colon will be taken.; A validated scintigraphic method to measure gastric, small bowel and colonic transit will be used.; Stool samples will be used to extract supernatants. These supernatants will be studied in using chamber set-up to determine barrier effects on T84 monolayers.
Observational model: Case-Control
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Post Infectious IBS Cases Post Infectious with no IBS Controls Healthy Volunteer Controls
      
Biospecimen description: 
      Blood, stool, and tissue samples