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Macromolecular transport in jejunal mucosa of children with severe malnutrition: a quantitative study
Insights
Malnutrition in children significantly increases intestinal permeability to macromolecules like horseradish peroxidase (HRP). This heightened permeability is due to increased transcellular absorption, not paracellular leakage, and improves with nutritional rehabilitation.
Area of Science:
- Gastroenterology
- Pediatric Nutrition
- Cell Biology
Background:
- Childhood malnutrition is a global health issue often associated with gastrointestinal dysfunction.
- Increased intestinal permeability is a suspected complication of malnutrition, impacting nutrient absorption and barrier integrity.
Purpose of the Study:
- To investigate small intestinal permeability to macromolecules in malnourished children.
- To differentiate between paracellular and transcellular pathways contributing to increased permeability.
- To assess the impact of nutritional rehabilitation on intestinal barrier function.
Main Methods:
- Assessed jejunal biopsies from malnourished children and after nutritional rehabilitation.
- Measured transepithelial horseradish peroxidase (HRP) fluxes using Ussing chambers.
- Evaluated intact and degraded HRP transport, alongside electrical parameters and D-Xylose tests.
Main Results:
- Transepithelial HRP fluxes were significantly higher in malnourished children compared to rehabilitated children.
- Increased permeability was attributed to enhanced transcellular absorption, not changes in paracellular conductance.
- Intratissue protein degradation remained unchanged during malnutrition.
Conclusions:
- Childhood malnutrition with diarrhea is linked to increased intestinal macromolecular permeability.
- The primary mechanism involves heightened transcellular absorption of proteins.
- Nutritional rehabilitation effectively restores intestinal barrier function, reducing macromolecular permeability.
Abstract:
Small intestinal permeability to horseradish peroxidase (HRP) was assessed in jejunal biopsies of malnourished children. Clinical examination, intestinal function (D-Xylose test), and the histological appearance of the mucosa were assessed in 14 children during the malnutrition phase and in eight children after 3 months of nutritional rehabilitation. Macromolecular permeability was evaluated by measuring transepithelial HRP fluxes from mucosa to serosa (JHRPms) using Ussing chambers. Intact HRP transport, i.e., nondegraded protein transport, was measured by enzyme assay, and tritiated HRP was concomitantly used to measure intact and degraded HRP fluxes (J[3H]HRPms). Electrical parameters (short-circuit current, potential difference, and ionic conductance) were also recorded. Transepithelial HRP fluxes were significantly higher during malnutrition (JHRPms = 8.85 +/- 1.44; J[3H]HRPms = 77.11 +/- 10.66 pmol X h-1 X cm-2) than in the same children after 3 months of nutritional rehabilitation (JHRPms = 2.94 +/- 1.10; J[3H]HRPms = 22.93 +/- 8.15 pmol X h-1 X cm-2). The total ionic conductance, which is an index of paracellular permeability, did not change significantly. Calculated intratissue degradation of the protein did not appear to alter during malnutrition. These results point to a clinical situation in which malnutrition with diarrhea in children is associated with increased intestinal permeability to macromolecules by a mechanism not related to any paracellular leak of the protein, but rather to increased transcellular absorption.