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OP001 Gut barrier dysfunction: a primary defect in twins with Crohn’s disease predominantly caused by genetic predisposition

Å.V. Keita1, C.M. Lindqvist2, Å. Öst3, C.D.L. Magana1, I. Schoultz2, J. Halfvarson4*

1Linköping University, Department of Clinical and Experimental Medicine, Linköping, Sweden, 2Örebro University, Department of Medical Sciences, Örebro, Sweden, 3Aleris Medilab, Department of Pathology and Cytology, Täby, Sweden, 4Örebro University, Department of Gastroenterology, Örebro, Sweden


The aetiology of the dysfunctional barrier in Crohn’s disease (CD) is poorly understood. By investigating twin pairs discordant for CD we aimed to assess whether the dysregulated barrier in CD represents a cause or a consequence of the inflammation and to evaluate the impact of genetics and environmental exposure on barrier function.


Ileal biopsies from 15 twin pairs discordant for CD (monozygotic n = 9, dizygotic n = 6) and 10 external controls were mounted in Ussing chambers to assess paracellular permeability to 51Cr-EDTA and transcellular passage to non-pathogenic E. coli K-12. Experiments were performed with and without provocation with acetylsalicylic acid (ASA). Immunofluorescence and ELISA were used to quantify the expression level of tight junction proteins in the biopsies.


Healthy co-twins and CD twins displayed increased 51Cr-EDTA permeability at 120 min both with ASA (p < 0.001) and without ASA (p < 0.001) when compared with controls (Figure 1). The difference was observed already at 20 min with ASA, when healthy co-twins were compared with external controls (p < 0.05). Stratification by zygosity revealed an increased permeability at 20 min both with ASA (p = 0.05) and without ASA (p < 0.05) in healthy monozygotic co-twins, but no statistical difference was observed between healthy dizygotic co-twins and external controls. Consistently, healthy monozygotic displayed an increased permeability at 20 min without ASA when compared with healthy dizygotic co-twins (p < 0.05). No difference in E. coli passage could be observed between groups. Immunofluorescence of the tight junction proteins claudin-5 and tricellulin showed lower levels in healthy co-twins (p < 0.05) and CD twins (p < 0.05) compared with external controls, while ELISA only showed lower tricellulin in CD compared with controls (p < 0.05).

Figure 1. Prevalence of treatments for Crohn’s disease patients on any given day during follow-up.

Figure 1. Paracellular permeability across biopsies mounted in Ussing chambers from twin pairs (n = 15) disconcordant for Crohn’s disease and external controls (n = 10). Experiments were performed with and without provocation to ASA for 20 and 120 min.


Our result indicates that barrier dysfunction is a primary defect in CD, since changes were predominantly seen in the healthy monozygotic co-twins. Moreover, passage of E. coli K-12 seems to be a consequence of inflammation rather than representing a primary defect.