title: Psychological comorbidity increases the risk for postinfectious IBS partly by enhanced susceptibility to develop infectious gastroenteritis.
abstract: Psychological factors increase the risk to develop postinfectious IBS (PI-IBS), but the mechanisms involved are unclear. As stress affects the immune system, we investigated the potential interaction between psychological factors, the immune response against infectious gastroenteritis (IGE) and the development of IGE and PI-IBS in a large cohort exposed to contaminated drinking water.
  
  
  
  18 620 people exposed to contaminated drinking water (norovirus, Giardia lamblia, Campylobacter jejuni) were invited to participate in a prospective controlled cohort study. They were asked to complete questionnaires assessing demographic, psychological and clinical data during the outbreak and 1 year later. At both time points, in-depth immune function (peripheral blood and rectal biopsies) was studied in a subgroup of subjects.
  
  
  
  1379 subjects completed the questionnaires during the outbreak, of which 271 developed IGE. Risk factors for IGE included younger age, pre-existing dyspepsia-like symptoms, anxiety and drinking contaminated tap water. Anxiety scores before the outbreak inversely correlated with interleukin-2-expressing CD4+ T cells (r=0.6, p=0.01, n=23). At follow-up, 34 of 172 (20%) IGE subjects developed IBS compared with 24/366 exposed participants (7%, p<0.0001, χ(2) test). A Th2 cytokine phenotype at time of infection was associated with increased risk for PI-IBS 1 year later. Except for increased B cell numbers, no evidence for systemic or rectal mucosal immune activation in PI-IBS was demonstrated at follow-up.
  
  
  
  Our study shows that the increased risk of patients with psychological comorbidity to develop PI-IBS may partly result from an increased susceptibility to develop IGE, possibly resulting from a Th2-immune bias.
  
  
  
  (ClinicalTrials.gov NCT01497847).
authors.affiliation: Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders, University Hospital Leuven, KU Leuven, Leuven, Belgium.
authors.forename: Mira M
authors.initials: MM
authors.lastname: Wouters
authors.affiliation: Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders, University Hospital Leuven, KU Leuven, Leuven, Belgium.
authors.forename: Sander
authors.initials: S
authors.lastname: Van Wanrooy
authors.affiliation: Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium Autoimmune Genetics Laboratory, VIB, Leuven, Belgium.
authors.forename: Anh
authors.initials: A
authors.lastname: Nguyen
authors.affiliation: Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium Autoimmune Genetics Laboratory, VIB, Leuven, Belgium.
authors.forename: James
authors.initials: J
authors.lastname: Dooley
authors.affiliation: Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders, University Hospital Leuven, KU Leuven, Leuven, Belgium.
authors.forename: Javier
authors.initials: J
authors.lastname: Aguilera-Lizarraga
authors.affiliation: Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders, University Hospital Leuven, KU Leuven, Leuven, Belgium.
authors.forename: Winde
authors.initials: W
authors.lastname: Van Brabant
authors.affiliation: Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium Autoimmune Genetics Laboratory, VIB, Leuven, Belgium.
authors.forename: Josselyn E
authors.initials: JE
authors.lastname: Garcia-Perez
authors.affiliation: Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders, University Hospital Leuven, KU Leuven, Leuven, Belgium.
authors.forename: Lukas
authors.initials: L
authors.lastname: Van Oudenhove
authors.affiliation: Laboratory of Clinical Virology, Rega Institute for Medical Research, University Hospital Leuven, Leuven, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Van Ranst
authors.affiliation: Department of Microbiology, University Hospital Leuven, KU Leuven, Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Verhaegen
authors.affiliation: Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium Autoimmune Genetics Laboratory, VIB, Leuven, Belgium.
authors.forename: Adrian
authors.initials: A
authors.lastname: Liston
authors.affiliation: Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders, University Hospital Leuven, KU Leuven, Leuven, Belgium.
authors.forename: Guy
authors.initials: G
authors.lastname: Boeckxstaens
mesh_terms: D000328:Adult; D001530:Belgium / Q000453:epidemiology; D001706:Biopsy / Q000379:methods; D002169:Campylobacter Infections / Q000150:complications / Q000453:epidemiology / Q000276:immunology; D016123:Campylobacter jejuni / Q000302:isolation & purification; D015897:Comorbidity; D016207:Cytokines / Q000032:analysis; D004196:Disease Outbreaks; D004198:Disease Susceptibility / Q000523:psychology; D060766:Drinking Water / Q000032:analysis / Q000382:microbiology; D005260:Female; D005759:Gastroenteritis / Q000150:complications / Q000453:epidemiology / Q000276:immunology / Q000382:microbiology; D016829:Giardia lamblia / Q000302:isolation & purification; D005873:Giardiasis / Q000150:complications / Q000453:epidemiology / Q000276:immunology; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000175:diagnosis / Q000209:etiology / Q000523:psychology; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D011569:Psychiatric Status Rating Scales; D012007:Rectum / Q000382:microbiology / Q000473:pathology; D012307:Risk Factors; D013315:Stress, Psychological / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology / Q000503:physiopathology; D011795:Surveys and Questionnaires
chemical_list: D016207:Cytokines; D060766:Drinking Water
keywords: IGE; IRRITABLE BOWEL SYNDROME