Jejunal mucosal injury and restitution: role of hydrolytic products of food digestion

Abstract

The effects of hydrolytic products of carbohydrate, protein, and lipid digestion on jejunal mucosal injury and restitution were assessed in anesthetized rats. Mucosal epithelial integrity was continuously monitored by measuring the blood-to-lumen clearance of 51Cr-labeled EDTA. Perfusion of the lumen with hydrolyzed casein (3%) or glucose (150 mM) did not affect 51Cr-EDTA clearance compared with saline controls. By contrast, perfusion with emulsified lipids (20 mM sodium taurocholate and 10-40 mM oleic acid) increased 51Cr-EDTA clearance in a dose-dependent manner. The lipid-induced increase in 51Cr-EDTA clearance returned toward control levels when the lipid infusion was terminated and saline perfusion resumed. Histological evaluation of jejunal mucosa indicated that the epithelial lining of the villous tips was damaged during lipid infusion and that restitution of the lining occurred within 50 min after resumption of saline perfusion. In vitro studies indicated that neither glucose nor hydrolyzed casein affected the integrity of rat intestinal epithelial cell (IEC-18) monolayers in culture. Oleic acid emulsified in rat hepatic bile produced a dose-dependent disruption of the epithelial monolayer. Biochemical determination of lipid peroxidation products in vivo and in vitro yielded negative results, indicating that the lipid-induced epithelial cell injury was not due to lipid peroxidation. Because the concentrations of the various nutrients used in the present study are similar to those measured in postprandial chyme, the findings of the present study suggest that the intestinal epithelium is injured and restitutes during the normal course of digestion and absorption of a meal.

Chylomicrons promote intestinal absorption of lipopolysaccharides

“…In theory, dietary fat could increase LPS absorption in several ways. One way would be through promotion of paracellular uptake of macromolecules as a result of deleterious effects of fatty acids on tight-junction integrity (19). Our data do not support such a mechanism, for two reasons.…”

“…One possibility is that dietary fat promotes paracellular leakage of LPS across the intestinal epithelium. This is supported by the recent observations that intestinal-epithelial tight-junction integrity is compromised in obese mice (18) and by studies demonstrating that experimental intestinal luminal exposure to oleic acid (OA) can cause small-intestinal epithelial damage (19,20). An alternative possibility could be that LPS enters the body proper by transcellular transport through intestinal epithelial cells.…”

Fatty Acid-Induced Injury in Developing Piglet Intestine: Effect of Degree of Saturation and Carbon Chain Length

“…These changes may involve subtle alttl.ations in permeability or, at higher detergent concentrations, more drastic effects such as membrane lysis and fusion (1 1). A concentration-dependent injury has also been observed in intestinal mucosa of developing piglets (7) and adult rats (8) after perfusion with bile acidsolubilized oleic acid. In fact, the concentration of fatty acids used in this study (5 mM) has been shown to produce a 20-fold increase in mucosal permeability in I-d-old piglet jejunum (7) and is associated with cell injury observed with light and electron microscopy (7).…”

“…Despite the important nutritional value of dietary fatty acids, these compounds have been implicated in the pathophysiology of intestinal mucosal injury in developing (6,7) and adult animals (8,9). We have shown that perfusion of developing piglet intestine with oleic acid, a long-chain dietary fatty acid, produces dose-dependent increases in mucosal permeability as quantitated by the plasma-to-lumen clearance of 5'Cr-labeled EDTA.…”

The enteric nervous system of P2Y13 receptor null mice is resistant against high-fat-diet- and palmitic-acid-induced neuronal loss

“…An interesting finding was the ileal mucosal thinning observed in both P2Y 13 +/+ and P2Y 13 −/− mice fed with HFD. Previous studies have shown lipid infusions, unlike other nutrients, to cause a mucosa barrier impairment in the rat small intestine [26].…”