Small Intestinal Epithelial Barrier Research Articles

Acetylation of hydroxytyrosol enhances its transport across differentiated Caco-2 cell monolayers

Hydroxytyrosol and hydroxytyrosyl acetate are two well-known phenolic compounds with antioxidant properties that are present in virgin olive oil. Since the in vivo biological activity of polyphenols is dependent on their intestinal absorption and metabolism, the absorption of hydroxytyrosol and hydroxytyrosyl acetate and the extent to which they are conjugated and metabolised during transfer across intestinal Caco-2/TC7 cell monolayers, was investigated. LC-DAD and LC-MS were used for the quantification and identification of metabolites. Further evidence was obtained by observing metabolite susceptibility to β-glucuronidase treatment and by comparison of products of in vitro conjugation reactions of authentic phenolics with those produced by the CaCo-2 cells. Homovanillyl alcohol was the only conjugate detected as a result of hydroxytyrosol metabolism, and accounted for 20% of the total metabolites detected in the basolateral compartment after 2 h of incubation. Hydroxytyrosyl acetate was largely converted into free hydroxytyrosol (38.4%) and subsequently metabolised into homovanillyl alcohol (6.7%). In addition, hydroxytyrosyl acetate glucuronide (17.4%) together with non-metabolised hydroxytyrosyl acetate (37.5%) were also detected. Both hydroxytyrosyl acetate and hydroxytyrosol were transferred across human Caco-2/TC7 cell monolayers, but the acetylated compound exhibited an apparent permeability (Papp AP→BL/Papp BL→AP) 2.1-fold higher than free hydroxytyrosol. For both compounds, all conjugates were preferentially transported to the basolateral side. These results show that the acetylation of hydroxytyrosol significantly increases its transport across the small intestinal epithelial cell barrier, and supports further research into hydroxytyrosyl acetate as a hydroxytyrosol prodrug offering enhanced bioavailability.

Lactobacillus plantarum prevents the development of colitis in IL-10-deficient mouse by reducing the intestinal permeability

It is reported that defects exist in the small intestinal epithelial barrier of inflammatory bowel disease, which might be associated with increased intestinal permeability at a very early stage. Our study aims to investigate the role of Lactobacillus plantarum on the decrease of epithelial permeability and the further protective effects on the intestinal epithelial barrier using the IL-10-deficient mouse model. Our study showed that tight junction associated proteins were increased after the pre-treatment of L. plantarum by fluorescence staining, western blot, real-time PCR and transmission electron microscope. Oral gavage of milk containing L. plantarum was effective in decreasing small intestinal permeability using methods of Ussing chamber assay and sugar probe. Assay of pro-inflammatory cytokines IFN-γ, TNF-α, MPO, and colonic histology by ELISA showed protective effects of L. plantarum on the intestinal epithelial barrier. Therefore, L. plantarum may prevent the development of colitis in IL-10-deficient mice by blocking changes in the expression of TJ proteins, TJ structure and intestinal permeability.

Reducing small intestinal permeability attenuates colitis in the IL10 gene-deficient mouse

Background:Defects in the small intestinal epithelial barrier have been associated with inflammatory bowel disease but their role in the causation of disease is still a matter of debate. In some...

Small Intestine Epithelial Barrier Function Is Compromised in Pigs with Low Feed Intake at Weaning

Compromising alterations in gastrointestinal architecture are common during the weaning transition of pigs. The relation between villous atrophy and epithelial barrier function at weaning is not well understood. This study evaluated in vitro transepithelial transport by Ussing metabolic chambers, local alterations in T-cell subsets and villous architecture at low energy intake level and their relation with lactose/protein ratios in the diet. Pigs (n = 66, 26 d old) were sampled either at weaning (d 0), d 1, 2 or 4 postweaning. Piglets received one of three diets at a low energy intake level, which differed in lactose and protein ratio as follows: low lactose/high protein (LL/HP), control (C), or high lactose/low protein (HL/LP). Mean digestible energy intake was 648 kJ/pig on d 1, 1668 kJ/pig on d 2, 1995 kJ/pig on d 3 and 1990 kJ/pig on d 4 postweaning. The CD4(+)/CD8(+) T-lymphocytes ratio decreased after weaning (P < 0.05). Decreased paracellular transport (P < 0.01), greater villous height (P < 0.01), shallower crypts and lower villus/crypt ratios (P < 0.01) were observed on d 2 compared with d 0. Piglets consuming the HL/LP diet tended to have less paracellular transport (P < 0.10) and greater villous height (P < 0.10) compared with piglets fed the other diets. During the first 4 d postweaning, the effect of diet composition on mucosal integrity was not as important as the sequential effects of low energy intake at weaning. Stress and diminished enteral stimulation seem to compromise mucosal integrity as indicated by increased paracellular transport and altered T-cell subsets.

Phagocytic and intestinal endothelial and epithelial barrier function during the early stage of small intestinal ischemia and reperfusion injury.

The effects of intestinal ischemia and reperfusion (I/R) on small intestinal mucosal endothelial and epithelial barrier integrity and phagocytic function were assessed in rats subjected to 20- or 40-min mesenteric ischemia and a 3-h reperfusion. The results showed that human serum albumin (125I-HSA) flux through the endothelial layer to the interstitial space increased as did 125I-HSA clearance from blood to the gut lumen and 131I-HSA flux from the gut lumen to the interstitial space in rats with I/R. E. coli adhering to microvilli, invading and passing into the microvessels, were noted on the small intestinal mucosa in animals subjected to 40-min ischemia and a 3-h reperfusion. Phagocytic function increased, especially in the small intestinal wall, lungs, liver, and spleen in the groups with I/R, correlating with the length of ischemia. The results imply that both endothelial and epithelial barrier integrity is impaired in the early phase after I/R and that the epithelial barrier more effectively restricts macromolecular leakage compared with the endothelial barrier. I/R impairs the intestinal barrier not only by causing tissue hypoxia but also by activating the phagocytic system and aggravating barrier damage, which finally may result in bacterial translocation and remote organ dysfunction.