Gut Barrier Dysfunction-A Primary Defect in Twins with Crohn's Disease Predominantly Caused by Genetic Predisposition.
J Crohns Colitis
; 12(10): 1200-1209, 2018 11 09.
Article
en En
| MEDLINE
| ID: mdl-29659773
ABSTRACT
Background and Aims:
The aetiology of Crohn's disease is poorly understood. By investigating twin pairs discordant for Crohn's disease, we aimed to assess whether the dysregulated barrier represents a cause or a consequence of inflammation and to evaluate the impact of genetic predisposition on barrier function.Methods:
Ileal biopsies from 15 twin pairs discordant for Crohn's disease [monozygotic n = 9, dizygotic n = 6] and 10 external controls were mounted in Ussing chambers to assess paracellular permeability to 51Chromium [Cr]-EDTA and trancellular passage to non-pathogenic E. coli K-12. Experiments were performed with and without provocation with acetylsalicylic acid. Immunofluorescence and ELISA were used to quantify the expression level of tight junction proteins.Results:
Healthy co-twins and affected twins displayed increased 51Cr-EDTA permeability at 120 min, both with acetylsalicylic acid [p < 0.001] and without [p < 0.001] when compared with controls. A significant increase in 51Cr-EDTA flux was already seen at 20 min in healthy monozygotic co-twins compared with controls [p≤0.05] when stratified by zygosity, but not in healthy dizygotic co-twins. No difference in E. coli passage was observed between groups. Immunofluorescence of the tight junction proteins claudin-5 and tricellulin showed lower levels in healthy co-twins [p < 0.05] and affected twins [p < 0.05] compared with external controls, while ELISA only showed lower tricellulin in Crohn's disease twins [p < 0.05].Conclusion:
Our results suggest that barrier dysfunction is a primary defect in Crohn's disease, since changes were predominantly seen in healthy monozygotic co-twins. Passage of E. coli seems to be a consequence of inflammation, rather than representing a primary defect.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedad de Crohn
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Aspirina
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Radioisótopos de Cromo
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Ácido Edético
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Escherichia coli K12
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Proteína 2 con Dominio MARVEL
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Claudina-5
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Íleon
Límite:
Adult
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
J Crohns Colitis
Asunto de la revista:
GASTROENTEROLOGIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Suecia