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PubMed2005

Intestinal metabolism of PAH: in vitro demonstration and study of its impact on PAH transfer through the intestinal epithelium.

Food would seem to be one of the main ways of animal and human contamination with polycyclic aromatic hydrocarbons (PAHs). In vivo studies suggest a transfer in intestinal epithelium by diffusion, which appears extensively governed by the physicochemical properties of PAHs, particularly lipophilicity. However, other mechanisms, such as metabolism, are considered to intervene. Our work aimed at testing in vitro intestinal metabolism and defining its impact on transepithelial transport of PAHs. Caco-2 cells were cultivated on permeable filters and incubated with 14C-labeled benzo[a]pyrene (BaP), pyrene (Pyr), and phenanthrene (Phe), which differ in their physicochemical properties. The results showed that the cells were able to metabolize the compounds. In basal media, Phe appeared to be the least hydroxylated molecule (45% after a 6-h exposure), followed by Pyr (65%) and finally BaP (96%). Inhibition of PAH metabolism showed a determinant effect on kinetics profiles. Transfer in the basal compartment of BaP, Pyr, and Phe radioactivities was, respectively, 26, 4, and 2 times lower with inhibitors, corroborating that intestinal metabolism of PAHs would have a positive impact on their transfer, an impact that increased with their lipophilicity. Furthermore, after a 6-h incubation, metabolites were also detected in apical medium. These findings suggested that intestinal metabolism might play a key role in intestinal barrier permeability and thus in the bioavailability of tested micropollutants.

Benzo(a)pyrene↗
PubMed1998

Presence of adherent Escherichia coli strains in ileal mucosa of patients with Crohn's disease.

BACKGROUND & AIMS: Infectious agents are suspected of being involved in the pathogenesis of Crohn's disease. This study was designed to look for the presence of virulent Escherichia coli strains associated with the ileal mucosa of patients with Crohn's disease. METHODS: E. coli strains were recovered from resected chronic ileal lesions (n = 20), neoterminal ileum after surgery from patients with (n = 19) and without (n = 11) endoscopic recurrence, and controls (n = 13). Bacterial adhesion was determined in vitro using intestinal cell lines; other associated virulence factors were assessed by DNA hybridization and polymerase chain reaction experiments. RESULTS: None of the strains harbored any of the virulence factor-encoding genes of E. coli involved in acute enteric diseases. However, mannose-resistant adhesion to differentiated Caco-2 cells was found for 84.6% and 78.9% of the E. coli strains isolated from chronic and early recurrent lesions, respectively, compared with 33% of controls (P < 0.02). In addition, 21.8% of the strains induced a cytolytic effect by synthesis of an alpha-hemolysin. CONCLUSIONS: E. coli strains isolated from the ileal mucosa of patients with Crohn's disease adhere to differentiated intestinal cells and may disrupt the intestinal barrier by synthesizing an alpha-hemolysin.

Adult↗
PubMed2000

Polyunsaturated fatty acids reduce non-receptor-mediated transcellular permeation of protein across a model of intestinal epithelium in vitro.

BACKGROUND: Dietary polyunsaturated fatty acids influence the natural history of intestinal inflammatory diseases. Varying the types of long-chain fatty acids that are exposed to cells alters the physicochemical properties of cell membranes. This study aimed to determine whether such variations alter transcellular and paracellular permeability in intestinal epithelium. METHODS: Monolayers of Caco-2 cells, allowed to differentiate by culturing for 7 days following confluence, were used as the model for intestinal epithelium. Paracellular permeability was assessed by measurement of transepithelial resistance, while transcellular permeability was assessed by the transepithelial flux of horseradish peroxidase. RESULTS: Exposure of the cells to 100 micromol/L of palmitic acid, oleic acid, eicosapentaenoic acid, or linoleic acid, was not toxic to cells (measured by leakage of lactate dehydrogenase), and altered cell membrane fatty acid composition (as measured by gas chromatography). Flux of horseradish peroxidase was significantly affected by 24 h fatty acid exposure (P= 0.038, ANOVA), being decreased by 23 +/- 6% (mean +/- SEM) by eicosapentaenoic acid and 25 +/- 3% by linoleic acid. Oleic acid, palmitic acid and butyrate, had no effect. Transepithelial resistance also varied significantly across the treatment groups (P< 0.001) due to a 28 +/- 5% increase induced by butyrate. The long-chain fatty acids had no effect. CONCLUSIONS: Both omega-3 and omega-6 polyunsaturated fatty acids reduce transcellular, non-receptor-mediated permeation of proteins across differentiated Caco2 cell monolayers, without altering paracellular permeability. Alteration of intestinal barrier function should be considered as a possible mechanism of action of dietary polyunsaturated fatty acids.

Butyrates↗
PubMed1986

[Membrane digestion and some general problems in physiology].

A number of general problems arising from investigations of various aspects of membrane digestion has been considered in the paper. The development of this field of knowledge allowed to characterize from a new point of view the role of glycocalix, molecular physiology of intestinal enzymes, the role of recirculation of membrane proteins and intestinal barrier as well as the scale of membrane hydrolysis and transport in conditions approximated to physiological ones. The level of membrane hydrolysis and transport in vivo is several times that of in vitro experiments and of acute experiments in situ. From the data obtained it is evident that some present concepts of the level efficiency of in vivo physiological processes in the small intestine and mechanisms of their regulation ought to be reconsidered.

Amino Acids↗
PubMed2002

Uptake of colostral leukocytes in the intestinal tract of newborn calves.

The role of colostral immunoglobulins for the protection of newborn calves has been studied extensively, but little is known about the importance of colostral leukocytes. To study the uptake of colostral leukocytes in the intestine of calves and to determine preferential sites for this uptake, FITC-labelled colostral cells derived from the respective dams were injected into intestinal loops with/without Peyer's patches of three male Holstein Frisian calves about 5h post natum. In adjacent loops, PBS was injected as control. Loops were excised after an exposure of 1.5-2h. FITC-labelled material and cells were detected by the direct immunoperoxidase method in paraplast sections. Twenty-five consecutive sections were evaluated from each localization. Uptake of labelled material and cells was observed in all three calves in the jejunal Peyer's patch and in two calves in the ileal Peyer's patch as well. In the jejunal Peyer's patch, labelled material and cells were present in epithelium, domes and sinuses around lymphoid follicles, whereas in the ileal Peyer's patch, they were found in the sinuses only. These findings confirm that uptake of colostral leukocytes through the intestinal barrier is possible and that the preferential route of uptake is through follicle-associated epithelium of Peyer's patches.

Animals↗
PubMed2005

Role of the intestinal tight junction modulator zonulin in the pathogenesis of type I diabetes in BB diabetic-prone rats.

Increased intestinal permeability has been observed in numerous human autoimmune diseases, including type-1 diabetes (T1D) and its' animal model, the BB-wor diabetic prone rat. We have recently described zonulin, a protein that regulates intercellular tight junctions. The objective of this study was to establish whether zonulin-dependent increased intestinal permeability plays a role in the pathogenesis of T1D. In the BB diabetic-prone rat model of T1D, intestinal intraluminal zonulin levels were elevated 35-fold compared to control BB diabetic-resistant rats. Zonulin up-regulation was coincident with decreased small intestinal transepithelial electrical resistance, and was followed by the production of autoantibodies against pancreatic beta cells, which preceded the onset of clinically evident T1D by approximately 25 days. In those diabetic prone rats that did not progress to diabetes, both intraluminal zonulin and transepithelial electrical resistance were similar to those detected in diabetic-resistant animal controls. Blockade of the zonulin receptor reduced the cumulative incidence of T1D by 70%, despite the persistence of intraluminal zonulin up-regulation. Moreover, treatment responders did not seroconvert to islet cell antibodies. Combined together, these findings suggest that the zonulin-induced loss in small intestinal barrier function is involved in the pathogenesis of T1D in the BB diabetic-prone animal model.

Animals↗
PubMed2001

Inhibitory effect and mechanism of acarbose combined with gymnemic acid on maltose absorption in rat intestine.

AIM: To compare the combinative and individual effect of acarbose and gymnemic acid (GA) on maltose absorption and hydrolysis in small intestine to determine whether nutrient control in diabetic care can be improved by combination of them. METHODS: The absorption and hydrolysis of maltose were studied by cyclic perfusion of intestinal loops in situ and motility of the intestine was recorded with the intestinal ring in vitro using Wistar rats. RESULTS: The total inhibitory rate of maltose absorption was improved by the combination of GA (0.1g/L-1.0 g/L) and acarbose (0.1 mmol/L-2.0 mmol/L) throughout their effective duration (P <0.05, U test of Mann-Whitney), although the improvement only could be seen at a low dosage during the first hour. With the combination, inhibitory duration of acarbose on maltose absorption was prolonged to 3h and the inhibitory effect onset of GA was fastened to 15 min. GA suppressed the intestinal mobility with a good correlation (r = 0.98) to the inhibitory effect of GA on maltose absorption and the inhibitory effect of 2 mmol/L (high dose) acarbose on maltose hydrolysis was dual modulated by 1g/L GA in vivo indicating that the combined effects involved the functional alteration of intestinal barriers. CONCLUSION: There are augmented effects of acarbose and GA,which involve pre-cellular and paracellular barriers. Diabetic care can be improved by employing the combination.

Acarbose↗
PubMed1997

The nasal-associated lymphoid tissue of adult mice acts as an entry site for the mouse mammary tumor retrovirus.

Mouse mammary tumor virus (MMTV) is a B type retrovirus transmitted to the suckling offspring through milk. MMTV crosses the intestinal barrier of neonates, initially infects the lymphoid cells of the Peyer's patches, and later spreads to all lymphoid organs and to the mammary gland. Adult mice can be infected systemically, but not by oral MMTV administration. In this study, we show that nasal administration of infected milk induces the infection of adult mice. Nasal MMTV infection shared the main features of systemic and neonatal intestinal MMTV infections: deletion of the superantigen (SAg)-reactive T cell subset from the peripheral T cell population, presence of viral DNA in lymphoid cells, and transmission of MMTV from mother to offspring. Viral DNA was restricted to the lungs and nasal-associated lymphoid tissue (NALT) 6 d after nasal infection. Furthermore, SAg-induced T cell proliferation was only detected in NALT. These results demonstrate that MMTV crosses the intact epithelium of the upper respiratory tract of adult mice and infects the lymphoid follicles associated with these structures.

Animals↗
PubMed2002

Current understanding of gastrointestinal immunoregulation and its relation to food allergy.

Tolerance to food antigens induced via the gut ("oral tolerance") appears to be a rather robust adaptive immune mechanism. However, the neonatal period is particularly critical in terms of mucosal defense, with regard to infections and priming for allergic disease. This is so because the intestinal barrier function provided by secretory antibodies, as well as the immunoregulatory network, is poorly developed for a variable period after birth. Notably, the postnatal development of mucosal immune homeostasis depends on the establishment of a normal commensal microbial flora and also on adequate timing and dose of dietary antigens when first introduced. In this context, breastfeeding appears to exert both shielding and positive regulatory effects. Altogether, the intestinal immune system normally seems rather fit for tolerance induction against innocuous antigens because most children with food allergy "outgrow" their problems, whereas airway allergy tends to persist.

Antigen-Presenting Cells↗
PubMed1991

L-carnitine and carnitine ester transport in the rat small intestine.

L-carnitine and its esters (acetyl-L-carnitine and propionyl-L-carnitine) at pharmacological doses (1, 5 and 10 mM) are absorbed by the rat jejunum by simple diffusion. Partition coefficients of carnitine esters determined in lipophilic media (diethyl ether/water and olive oil/water) are greater than that of L-carnitine. It would therefore seem that esters diffuse more easily through the lipid component of the intestinal barrier. The transport of acetyl- and propionyl-L-carnitine at pharmacological doses seems to be linearly and positively correlated with K+ transport but not with Na+ transport.

Acetylcarnitine↗
PubMed1992

Logistics and technique for combined hepatic-intestinal retrieval.

During a 13-month period, en bloc liver-small bowel cadaveric grafts were procured for seven children and one adult. All liver grafts functioned immediately, and all but one of the recipient patients recovered. Return of absorptive small bowel function was slow, but the integrity of the bacterial intestinal barrier was not disrupted. The described technique allows the procurement of other abdominothoracic organs, with the exception of the whole pancreas.

Adolescent↗
PubMed1991

[Intestinal permeability in patients with acquired immunodeficiency syndrome (AIDS)].

Intestinal permeability has been assessed as a parameter of the small intestinal barrier function in 33 patients with AIDS (WR 6), in 25 healthy volunteers, 32 patients with Crohn's disease, 18 patients with ulcerative colitis and in 12 patients with untreated coeliac disease. Permeability was measured by means of the 5 hour urinary excretion of lactulose and rhamnose after administration of these sugars (1 g rhamnose, 10 g lactulose) which allowed to calculate the urinary lactulose/rhamnose--ratio (L/R-r) as an index of intestinal permeability. Compared to the controls (L/R-r = 0.014 +/- 0.010) patients with AIDS had significantly increased lactulose/rhamnose--ratios (0.189 +/- 0.164; p less than 0.01) indicating abnormal permeation both of lactulose and rhamnose. This alteration of intestinal permeability was more pronounced than the significant increase of the L/R-r in the patients with either Crohn's disease or coeliac disease. However, intestinal permeability was not altered in the patients with ulcerative colitis. Among the patients with AIDS, the most abnormal permeability ratios were observed in two subjects with intestinal cryptosporidiosis. This investigation demonstrates by means of the "double sugar ratio", that intestinal permeability in patients with AIDS is highly abnormal, the impairment being even more abnormal than in patients with other small intestinal disease.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Host defense development in gut and related disorders.

The gastrointestinal tract serves as an important interface between ingested elements from the external environment and the internal milieu of the person. Maturation of this intestinal barrier appears to occur along with the normal development of other organ systems. Evidence is presented for this maturational process, and the relation of this immature barrier to certain disease states seen in the neonatal period (e.g., infectious diarrhea, necrotizing enterocolitis, and allergic disease) is discussed.

Celiac Disease↗
PubMed2004

Gut permeability in paediatric cardiac surgery.

BACKGROUND: Intestinal mucosal ischaemia can occur in infants and children during and after cardiac surgery. Severe decreases in mucosal perfusion may cause complications such as necrotizing enterocolitis and postoperative mortality. We investigated gut permeability in paediatric patients undergoing cardiac surgery using the dual sugar permeability test and absorption of two other saccharides. METHODS: Thirty-four patients undergoing palliative or corrective surgical procedures with and without cardiopulmonary bypass were investigated. Intestinal permeability was measured using 3-O-methyl-D-glucose, D-xylose, L-rhamnose and lactulose, given orally after induction of anaesthesia and 12 and 24 h later. RESULTS: Lactulose/rhamnose ratios were raised from the outset [median 0.39 (confidence interval 0.07-1.8 for patients undergoing operations without cardiopulmonary bypass and 0.30 (0.02-2.6) with cardiopulmonary bypass]. The highest lactulose/rhamnose ratios were recorded 12 h after surgery 0.32 (0.07-6.9), when cardiopulmonary bypass was used. This is approximately seven times the value expected in healthy children. There was an improvement in patients not undergoing cardiopulmonary bypass: 0.22 (0.03-0.85) 12 h and 0.11 (0-0.48) 24 h after induction of anaesthesia. Patients undergoing repair of aortic coarctation showed the fastest recovery: 0.09 (0.03-0.31) 12 h and 0.07 (0.04-0.35) 24 h after induction of anaesthesia. CONCLUSIONS: Patients with congenital heart defects have abnormal gut permeability when compared with healthy children of similar age. Cardiopulmonary bypass seems to affect the intestinal barrier morphologically (lactulose and rhamnose absorption) and functionally (3-O-methyl-D-glucose and D-xylose absorption).

Cardiopulmonary Bypass↗
PubMed1986

Effect of non-steroidal anti-inflammatory drugs and prostaglandins on the permeability of the human small intestine.

Intestinal permeability was estimated in healthy subjects after ingestion of aspirin (1.2+1.2 g), ibuprofen (400+400 mg) and indomethacin (75+50 mg) at midnight and an hour before starting a 51chromium labelled ethylenediaminetetraacetate absorption test. Intestinal permeability increased significantly from control levels following each drug and the effect was related to drug potency to inhibit cyclooxygenase. Intestinal permeability increased to a similar extent after oral and rectal administration of indomethacin showing that the effect is systemically mediated. Prostaglandin E2 decreased intestinal permeability significantly but failed to prevent the indomethacin induced increased intestinal permeability. These studies show that non-steroidal anti-inflammatory drugs disrupt the intestinal barrier function in man and suggest that the morphological correlates of the damage may reside at the level of the intercellular junctions.

Adult↗
PubMedDate not supplied

Glutamine: an essential amino acid for the gut.

Glutamine is a non-essential amino acid which is produced in sufficient amount by the healthy human body. From experimental work it is known that glutamine is an important nutrient for rapidly dividing cells such as cells from the immune system and the gut. During several conditions a lack of glutamine may occur. This will result in functional disturbances of the immune system and/or the gut. Glutamine is produced mainly by the muscle tissue. A decrease in muscle mass during nutritional depletion may result in decreased glutamine production capacity. Furthermore during critical illness, there is an increased demand for glutamine probably as a result of an increased utilization by the immune system. In addition, patients receiving standard parenteral nutrition do not receive glutamine, until recently, commercial parenteral nutrition did not contain glutamine because of instability of this amino acid during prolonged storage. One of the important functions of the gut is to prevent migration of bacteria and/or toxins from the gut lumen into the systemic circulation. A lack of glutamine may result in deterioration of this intestinal barrier. Supplementation of glutamine to certain patients could be essential. The relation between glutamine and the gut in several situations (nutritional depletion, critical illness, parenteral nutrition) is discussed in this paper.

Amino Acids, Essential↗
PubMed2007

Intestinal permeability in different feedings in infancy.

AIM: To determine the intestinal permeability (IP) as a marker of intestinal epithelial integrity in formula-fed infants compared with healthy breast-fed infants. METHODS: IP was measured in 57 healthy infants less than 4 months old. A dual sugar test with lactulose and mannitol was performed. Three urinary ratios were established: lactulose/mannitol (L/M), lactulose/creatinine (L/C) and mannitol/creatinine (M/C). Five groups were studied: breast-fed (n = 11), prebiotic supplemented formula (n 17), nucleotides supplemented formula (n = 9), LC-PUFA supplemented formula (n = 9) and LC-PUFA and nucleotides supplemented formula (n = 11). RESULTS: We have not found any difference in IP between breast-fed and formula-fed infants nor when the different formulas are compared with each other. The indirect information of the paracellular pathway by the ratio L/C and the transcellular route by the ratio M/C reflects some difference when the ingredients added are fructooligosaccharides and galactooligosaccharides, expressing a higher degree of lactulose permeation with respect to mannitol. When LC-PUFA supplementation was evaluated a lesser ratio of L/C was found, expressing intestinal barrier related to a process of epithelial tight. CONCLUSIONS: The most important factor in the maintenance of the integrity of epithelial barrier function is probably the delivery of nutrients in the gastrointestinal tract. The role of the different ingredients added should be clarified.

Animals↗
PubMed1991

The effect of elemental diet on intestinal permeability and inflammation in Crohn's disease.

This study examines whether treatment of acute Crohn's disease with an elemental diet improves intestinal integrity and inflammation as assessed by a 51Cr-labeled ethylenediaminetetraacetatic acid (EDTA) permeability test and the fecal excretion of 111In-labeled autologous leukocytes, respectively. Thirty-four patients with active Crohn's disease completed a 4-week treatment course with an elemental diet. Active disease was characterized by increased intestinal permeability [24-hour urine excretion of orally administered 51Cr-EDTA, 6.4% +/- 0.6% (mean +/- SE); normal, less than 3.0%] and by high fecal excretion of 111In-labeled leukocytes (14.2% +/- 1.1%; normal, less than 1.0%). Twenty-seven (80%) went into clinical remission, usually within a week of starting treatment. After 4 weeks of treatment, there was a significant decrease in both the urine excretion of 51Cr-EDTA (to 3.4% +/- 0.5%; P less than 0.01) and the fecal excretion of 111In (to 5.7% +/- 1.0%; P less than 0.001), indicating that such treatment is not just symptomatic. A framework for the mechanism by which elemental diet works, centering around the importance of the integrity of the intestinal barrier function, is proposed, and also appears to provide a logical explanation for some relapses of the disease.

Acute Disease↗