Clustering of increased small intestinal permeability in families with Crohn's disease

Gastroenterology. 1997 Sep;113(3):802-7. doi: 10.1016/s0016-5085(97)70174-4.


Background & aims: Small intestinal permeability is increased in a proportion of patients with Crohn's disease (CD) and a subset of their healthy relatives. A primary permeability defect was postulated in the pathogenesis of the disease. The aim of this study was to identify a possible genetic pattern in the distribution of CD and/or abnormal permeability.

Methods: Differential urinary excretion of lactulose and mannitol (L/ M) in complete CD families was determined. Controls included healthy families and families with ulcerative colitis. Pedigrees were used to compare the distribution of CD and/or increased permeability.

Results: The L/M was significantly increased in patients with CD. Seventeen of 67 first-degree relatives (25%) had a ratio greater than the upper limit (P95 = 0.0170). Permeability results of CD families showed a highly significant familial aggregation. The lack of a genetic pattern in relation with CD and occurrence of disturbed permeability especially within generation, points toward a shared environmental factor. Five of 14 healthy spouses (36%) of patients with CD had also an increased permeability, and prevalence of increased permeability was not higher in families with known familial occurrence (P = 0.85).

Conclusions: This large family study confirms an increased permeability in a subset of healthy relatives of patients with CD. However, the absence of a typical family pattern and the high prevalence in spouses is in favor of a common nongenetic factor or a subclinical disease manifestation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Child
  • Child, Preschool
  • Cluster Analysis
  • Crohn Disease / genetics*
  • Crohn Disease / metabolism*
  • Crohn Disease / urine
  • Female
  • Humans
  • Intestine, Small / metabolism*
  • Lactulose / urine
  • Male
  • Mannitol / urine
  • Middle Aged
  • Pedigree
  • Permeability
  • Reference Values


  • Mannitol
  • Lactulose