Changes in macromolecular transport appear early in Caco-2 cells infected with a human rotavirus.

OBJECTIVE: Rotavirus is a major cause of viral gastroenteritis, but its interaction with intestinal mucosa is poorly understood. The aim of this study was to examine the effect of Wa rotavirus (VP7 serotype 1) on barrier function in confluent Caco-2 cell monolayers. Wa is the most common serotype causing severe diarrhoea in humans. MATERIAL AND METHODS. We examined light and electron microscopic morphology, macromolecular transport, paracellular permeability, electrical parameters, disaccharidases and cytoskeletal structure in Wa- and in control sham-infected cells using a homologous human virus-cell system resembling human infection. RESULTS: During the first 48 h following Wa infection, there was no evidence of loss of integrity or of cytopathic effect in the monolayer. A significant cytopathic effect was noticed after 48 h. Further studies examined the initial 24-h period during which there was no evidence of significant injury. Apical-to-basolateral transcytosis of the macromolecule horseradish peroxidase (HRP) was selectively inhibited at 4 and 24 h post-infection with Wa. There were no significant changes in basolateral-to-apical transcytosis, endocytosis or in apical-to-apical recycling of HRP after Wa infection. G- and F-actin levels were significantly reduced within an area corresponding to the viroplasm in Wa-infected cells but not elsewhere in the monolayer. CONCLUSIONS: The early stages of rotavirus infection, before gross epithelial injury, are associated with a selective reduction in the apical uptake and transcytosis of macromolecules. We speculate that this is an epithelial defence mechanism.

Influence of diet complexity on intestinal adaptation following massive small bowel resection in a preclinical model.

AIMS: To investigate the effect of dietary complexity on intestinal adaptation using a preclinical model. METHODS: Four-week-old piglets underwent a 75% proximal small bowel resection or transection operation (control). Post-operatively, animals received either pig chow (n = 15), polymeric formula (n = 9), polymeric formula plus fiber (n = 6), or elemental formula (n = 7). RESULTS: The weight gain of all groups was reduced compared with controls that were fed the same diet. Animals that had a resection, which were fed elemental formula, had significantly reduced weight gain compared with the other groups (4.7 4.2 vs 30.7 7.1 kg chow and 11.5 1.3 kg polymeric formula). Villus height was increased in the jejunum, ileum and terminal ileum of resected animals compared with controls in animals fed with pig chow, polymeric formula and elemental formula. The animals that had a resection had a significant reduction in the transepithelial conductance (10.4 5.5 vs 25.4 6.5 mS/cm2) and 51Chromium-EDTA flux (2.8 1.9 vs 4.8 4.9 microL/h per cm2) compared with the controls. CONCLUSIONS: A complex diet was found to be superior to an elemental diet in terms of the morphological and functional features of adaptation following massive small bowel resection.