Impact of caloric intake on parenteral nutrition-associated intestinal morphology and mucosal barrier function

Abstract

Background: Parenteral nutrition (PN) is known to induce villus atrophy, epithelial cell (EC) apoptosis, and increase mucosal permeability. The study hypothesized that increasing amounts of energy delivery to mice would result in the best outcome, with the least effects on the mucosa.

Methods: Mice were randomized to enteral controls (saline infusion with ad libitum enteral food) or to 1 of 3 PN groups (with no enteral nutrition): full (100% of daily average energy intake for the mouse), reduced (75% of energy intake) or very low (50% of energy intake). Mice received PN for 7 days. Mucosal morphology, EC apoptosis, and bacterial translocation were assessed.

Results: Villus height decreased significantly with decreasing levels of caloric intake and was significantly lower in all PN groups compared with controls. Body weight loss was significantly greater in PN groups vs controls and was greatest in mice with the lowest caloric delivery. A consistent trend toward a higher EC apoptotic index with decreasing caloric intake was observed, and apoptosis in all PN groups exceeded controls (2-fold). All PN groups demonstrated greater bacterial translocation than controls.

Conclusions: PN induces intestinal EC apoptosis and villus and crypt atrophy, even at 100% of predicted energy needs, and such changes increased with greater reduction of energy intake. This study supports a concept that lack of enteral nutrition, rather than absolute caloric levels, is responsible for many of the adverse effects of PN. The study also allows the investigators to better optimize a mouse model of PN delivery.

Figure 1

Body weight in all PN groups was significantly less compared with Control after 7 days of infusion (*p<0.01). Body weight loss was greatest in the Very Low group. (Percentage weight loss calculated as: [Initial weight − Final weight]/[Initial weight] × 100).

Figure 2

Progressively lower amounts of caloric delivery resulted in progressively greater degrees of mucosal atrophy. A: Very Low PN intestine villus; B: Reduced PN; C: Full PN and D: Enteral control. Photomicrographs are taken at 40 × magnification.