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Chronic T cell-mediated enteropathy in rural west African children: relationship with nutritional status and small
David I Campbell1, Simon H Murch, Marinos Elia
1Medical Research Council (UK), Keneba, The Gambia.
Insights
Tropical enteropathy in Gambian children shows chronic inflammation and altered immune responses, even before severe malnutrition develops. This intestinal condition impacts growth and may affect oral tolerance mechanisms.
Area of Science:
- Gastroenterology
- Immunology
- Pediatric Nutrition
Background:
- Childhood growth in The Gambia is often poor and resistant to nutritional interventions.
- This poor growth is linked to small bowel permeability and enteropathy.
- Previous studies highlight the need to understand the mucosal immune response in this context.
Purpose of the Study:
- To characterize the mucosal inflammatory response in rural Gambian children.
- To correlate this response with intestinal permeability and nutritional status.
- To compare findings with age-matched U.K. controls.
Main Methods:
- Small bowel biopsies from 38 Gambian children (0.5-3 years) with varying nutritional status.
- Immunohistochemical analysis of mucosal biopsies for inflammatory markers and cytokines.
- Morphometry and comparison with 19 U.K. control subjects.
Main Results:
- All Gambian children exhibited chronic cell-mediated enteropathy, irrespective of nutritional status.
- Elevated intraepithelial lymphocytes and CD25+ cells compared to controls.
- Worsening nutrition correlated with increased T cells, decreased B cells, and a shift towards proinflammatory cytokines (decreased TGF-β).
Conclusions:
- Tropical enteropathy is characterized by chronic cell-mediated inflammation (TH1 response) and precedes severe malnutrition (marasmus).
- Protein-energy malnutrition is associated with reduced mucosal regulatory immune responses.
- These immune alterations may impair oral tolerance mechanisms in affected children.
Abstract:
Previous studies from The Gambia have shown that poor childhood growth is resistant to all but the most intense nutritional intervention and highly dependent on small bowel permeability related to enteropathy. We thus aimed to characterize the mucosal inflammatory response in rural Gambian children in relation to intestinal permeability and nutritional status. Small bowel biopsies were taken from 38 rural Gambian children (age, 0.5-3 y) with a range of nutritional and clinical states (median weight z score, -4.6; range, 0.5 to -6.4), 75% of whom had diarrhea. Morphometry was performed with immunohistochemical analysis for a range of lineage and activation markers, including proinflammatory and regulatory cytokines, and related to current clinical status and gut permeability. Comparison was made with 19 age-matched U.K. controls. All Gambian children, regardless of nutritional status, had evidence of chronic cell-mediated enteropathy with crypt hyperplasia, villous stunting, and high numbers of intraepithelial lymphocytes. CD25+ cells were 20-fold higher than in U.K. controls. Although small bowel architecture was independent of nutritional status, T cell numbers rose and B cell numbers fell with worsening nutrition, and mucosal cytokine production became biased toward a proinflammatory response, with progressive decrease of transforming growth factor-beta expression. Tropical enteropathy predates the onset of marasmus and is characterized by a cell-mediated TH1 response. Protein-energy malnutrition is associated with reduction of regulatory immune responses in the mucosal microenvironment, potentially impairing the mechanisms of oral tolerance.