On the fiftieth anniversary. Postinfectious irritable bowel syndrome: mechanisms related to pathogens.

Gastrointestinal (GI) infections resulting from bacterial, viral, and parasitic pathogens predispose to postinfectious irritable bowel syndrome (PI-IBS) and other functional GI disorders. Existing literature supports the role of enterochromaffin cell hyperplasia, serotonin synthesis and reuptake, impaired barrier function, altered immune activation, and potentially mast cell activation in the pathophysiology of PI-IBS. The objective of this review was to summarize from the literature the characteristics of the pathogens commonly implicated in PI-IBS, their acute enteritis phases, and the changes seen in the postinfectious phase that may contribute toward development of IBS. A limitation of our current understanding is that the postinfectious GI sequelae reported in prior studies followed epidemic diarrheal outbreaks often involving more than one pathogen, or the studies focused on highly selected, tertiary referral patients. Understanding the mechanisms, natural history, and optimized management of individuals suffering PI-IBS following the more typical sporadic infection requires larger studies of PI-IBS following GI infections encountered in community settings. These studies should include genetic, physiological, and molecular studies to provide more generalizable information that can ultimately be used to diagnose, manage, and potentially prevent the development of PI-IBS.

Grover M ，Camilleri M ，Smith K ，Linden DR ，Farrugia G ... -  《-》

Psychological comorbidity increases the risk for postinfectious IBS partly by enhanced susceptibility to develop infectious gastroenteritis.

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).

Wouters MM ，Van Wanrooy S ，Nguyen A ，Dooley J ，Aguilera-Lizarraga J ，Van Brabant W ，Garcia-Perez JE ，Van Oudenhove L ，Van Ranst M ，Verhaegen J ，Liston A ，Boeckxstaens G ... -  《-》

Postinfectious irritable bowel syndrome: follow-up of a patient cohort of confirmed cases of bacterial infection with Salmonella or Campylobacter.

Gastrointestinal infections have been proposed to predict subsequent irritable bowel syndrome (IBS) but large-scale infectious events are rare and long-term data are missing. We identified 576 individuals with a Salmonella or Campylobacter infection between 2000 and 2009 that were followed by a short postal questionnaire asking for the presence of current symptoms in 2010. In case of agreement (n = 90), an extended postinfectious (PI)-IBS questionnaire was mailed including the Hospital Anxiety Depression Scale and the Patient Health Questionnaire. A total of 189 patients reported back (36%); 98 had a Salmonella and 91 had a Campylobacter infection, of which 56 reported persistent symptoms (9.7% of the initial sample). Fifty-one patients returned the PI-IBS questionnaire. Of 48 patients with complete data, 15 reported no or mild symptoms of abdominal pain or discomfort while 17 had moderate and 16 severe symptoms. Twenty-two met Rome IBS criteria, 14 (29%) reported GI symptoms before the infection. Patients with moderate and/or severe PI-IBS symptoms were significantly more often females, were more often infected by Salmonella than by Campylobacter, had more severe symptoms during the initial infection, and had more often GI symptoms prior to the infection. They reported higher anxiety, depression, and somatisation scores, but were not different with respect to acute stool habits. Nearly 10% of patients with an intestinal bacterial infection report postinfectious symptoms up to 10 years after the infectious event. They represent a clinically important population with high psychiatric comorbidity and somatic symptom burden.

Schwille-Kiuntke J ，Enck P ，Zendler C ，Krieg M ，Polster AV ，Klosterhalfen S ，Autenrieth IB ，Zipfel S ，Frick JS ... -  《-》

Giardia duodenalis induces paracellular bacterial translocation and causes postinfectious visceral hypersensitivity.

Irritable bowel syndrome (IBS) is the most frequent functional gastrointestinal disorder. It is characterized by abdominal hypersensitivity, leading to discomfort and pain, as well as altered bowel habits. While it is common for IBS to develop following the resolution of infectious gastroenteritis [then termed postinfectious IBS (PI-IBS)], the mechanisms remain incompletely understood. Giardia duodenalis is a cosmopolitan water-borne enteropathogen that causes intestinal malabsorption, diarrhea, and postinfectious complications. Cause-and-effect studies using a human enteropathogen to help investigate the mechanisms of PI-IBS are sorely lacking. In an attempt to establish causality between giardiasis and postinfectious visceral hypersensitivity, this study describes a new model of PI-IBS in neonatal rats infected with G. duodenalis At 50 days postinfection with G. duodenalis (assemblage A or B), long after the parasite was cleared, rats developed visceral hypersensitivity to luminal balloon distension in the jejunum and rectum, activation of the nociceptive signaling pathway (increased c-fos expression), histological modifications (villus atrophy and crypt hyperplasia), and proliferation of mucosal intraepithelial lymphocytes and mast cells in the jejunum, but not in the rectum. G. duodenalis infection also disrupted the intestinal barrier, in vivo and in vitro, which in turn promoted the translocation of commensal bacteria. Giardia-induced bacterial paracellular translocation in vitro correlated with degradation of the tight junction proteins occludin and claudin-4. The extensive observations associated with gut hypersensitivity described here demonstrate that, indeed, in this new model of postgiardiasis IBS, alterations to the gut mucosa and c-fos are consistent with those associated with PI-IBS and, hence, offer avenues for new mechanistic research in the field.

Halliez MC ，Motta JP ，Feener TD ，Guérin G ，LeGoff L ，François A ，Colasse E ，Favennec L ，Gargala G ，Lapointe TK ，Altier C ，Buret AG ... -  《-》

Role of gut pathogens in development of irritable bowel syndrome.

Grover M 《-》