Authors
M. FLORENS (1), S. VAN WANROOY (1), W. PEETERMANS (2), M. WOUTERS (1), W. VANBRABANT (3), J. DOOLEY (4), A. LISTON (5), G. BOECKXSTAENS (1) / [1] KU Leuven, Leuven, Belgium, Department of Chronic Diseases, Metabolism and Ageing, [2] UZ Leuven, Leuven, Belgium, algemene interne geneeskunde, [3] UZ Leuven, Leuven, Belgium, Clinical Trial Center, [4] KU Leuven, Leuven, Belgium, Laboratory of Genetics of Autoimmunity (VIB-KU Leuven Center for Brain & Disease Research), [5] KU Leuven, Leuven, Belgium, Center for Brain & Disease Research
Introduction
Psychological distress, the severity of infectious gastroenteritis (IGE) and the use of antibiotics during IGE are risk factors to develop post-infectious irritable bowel syndrome (PI-IBS). As most studies are retrospective in nature, data collected to assess risk factors may however not be accurate. Moreover, the role of immune activation in PI-IBS remains unclear mainly because tissue or blood samples collected prior to the infection are not available.
Aim
To identify predisposing clinical and psychological factors for the development of PI-IBS and immune changes evoked by an IGE episode and associated with persistent IBS symptoms.
Methods
101 subjects traveling to high risk areas of IGE were asked to participate in a prospective study consisting of 4 visits: before travel, 2 weeks, 6 months and 1 year after travel. At each visit, subjects completed questionnaires on psychological profile (HADS, PHQ-12), bowel habits (Bristol Stool Scale, stool frequency) and gastrointestinal symptoms (GSRS and Rome III). Blood samples were collected for peripheral blood mononuclear cell isolation and rectal biopsies were taken. The IGE episode was self-assessed with respect to severity, duration and bowel habits. PI-IBS was diagnosed using the Rome III criteria and subjects with persistent post-infectious abdominal complaints (PI-AC, score>5) were identified using a composite score of loose stools (0-6), urgency (0-6) and abdominal pain (0-4).
Results
47 of the 101 subjects reported IGE during travel. After 1 year, 2 subjects (4%) were diagnosed with PI-IBS and 8 (17%) subjects presented with PI-AC. The mean pre-travel somatization (PI-AC: 5.6 ± 2.8 vs non PI-AC: 2.9 ± 2.5, p=0.01) and anxiety score (PI-AC: 6.3 ± 3.0 vs non PI-AC: 4.2 ± 3.4, p=0.04) were significantly higher in PI-AC versus non PI-AC. Of note, anxiety and depression scores of the total population were significantly lower compared to those reported in previous studies (anxiety: 3.5 ± 2.8, depression: 1.6 ± 2.2 vs 4.4 ± 3.6 and 3.3 ± 3.4 in Wouters et al. 2015, p<0.01). Binary logistic regression analysis identified basal stool consistency score, IGE severity and anxiety score as risk factors for PI-AC. Peripheral blood mononuclear cells analysis showed no differences in Th1, Th2, Th17, regulatory T cells or B cell populations in subjects with PI-AC versus non PI-AC. Additionally, no differences in inflammatory gene expression were observed in the acute phase (2 weeks) or after 1 year of follow-up.
Conclusions
The incidence of PI-IBS in healthy subjects who developed IGE was only 4%, while 17% of infected individuals continued to report PI-AC. The low incidence in our study may be due to the low anxiety scores of the study population, suggesting a selection bias of subjects that are not concerned to provide repetitive rectal biopsies. Risk factors to develop PI-AC are pre-travel stool consistency score, IGE severity and anxiety score, while no role for persistent immune activation could be detected.
