SEARCH · PubMed Health

Results for “Intestinal Barrier Function”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,135 records · Page 63Linked to original sources

PubMed2003

Colonic mucin: methods of measuring mucus thickness.

Mucus is a water-insoluble gel secreted by the gastrointestinal tract. It exists as a protective gel layer adherent to the epithelial surface of the stomach, small intestine and colon. The mucus gel is composed of 1-10 % (w/v) mucin glycoprotein in a plasma-like fluid. Since the mucus gel is predominantly water, standard histological techniques dehydrate the mucus, making visualisation of the functional barrier difficult. Specialist techniques have been developed to enable visualisation of the intact mucus layer. A simple histological method using snap-frozen tissue, sectioned with a cryostat and stained with modified periodic acid-Schiffs/Alcian blue in mucus-preserving conditions will be described. A second powerful in vivo animal model is described which enables measurement of mucus secretion over time. The use of these two methods has allowed the characterisation of the normal mucus layer in the colon and the determination of how it is affected by disease and dietary intervention, in particular the effect of dietary fibre, and evidence that fibre deficiency results in colonic mucosal fragility is presented.

Animals↗

PubMed2005

Prevention of infectious complications in surgical patients: potential role of probiotics.

Infectious complications in surgical patients often originate from the intestinal microflora. In the critically ill patient, small bowel motility is disturbed, leading to bacterial overgrowth and subsequent bacterial translocation due to dysfunction of the gut mucosal barrier. The optimal prophylactic strategy should act on all these factors, but such a strategy is not yet available. For several decades, antibiotic prophylaxis to prevent translocation of pathogenic bacteria has been studied with conflicting results. Selective decontamination of the digestive tract has shown good results, but fear for bacterial multiresistance has prevented worldwide implementation. In recent years, probiotics, living bacteria with a potential beneficial effect to their host, have shown promising results in several randomized placebo-controlled trials. Currently, in vitro and experimental research focuses on the effects of probiotics on the microflora responsible for gut-derived infections, structural mucosal barrier function and the immune system.

Acute Disease↗

PubMed1992

Intestinal fuels: glutamine, short-chain fatty acids, and dietary fiber.

In recent years, considerable research has focused on the physiologic effects and clinical uses of three dietary constituents thought to be trophic to the intestinal tract in human beings: glutamine, short-chain fatty acids (SCFAs), and dietary fiber. Glutamine is an important nitrogen-carrying amino acid that may be "conditionally essential" in certain disease states to support the gut barrier and immune function and overall protein use. Colonic irrigations with SCFA preparations have demonstrated enhanced healing of bowel tissue in animals and human beings. Dietary fiber supports bacterial SCFA production, normal stool output, and the gut barrier and immune function. However, optimal fiber doses for various medical conditions are not known, and the risk for gastrointestinal (GI) obstruction, diarrhea, gas, and bloating necessitates careful selection of patients and daily monitoring of fiber tolerance. A review of the current literature indicates that widespread use of glutamine and SCFA additives parenterally and enterally awaits further evidence of safety and efficacy in human beings, establishment of appropriate doses, and advances in formulation technology. Administration of dietary fiber to enhance bowel motility should be considered in long-term tube-fed patients with intact GI function and sufficient fluid tolerance to permit hydration of fiber. Industrywide agreement on fiber analysis methods and labeling standards (eg, fiber fermentability vs solubility) would facilitate selection of enteral products. To streamline studies and optimize research efforts in future clinical trials, standard criteria for evaluating GI function, diarrheagenic factors, and intestinal outcome variables should be established.

Animals↗

PubMed2001

Monocyte/macrophage activation by normal bacteria and bacterial products: implications for altered epithelial function in Crohn's disease.

Intestinal immune cells are less reactive than those in the peripheral blood; however, such cells from patients with Crohn's disease may be more responsive to bacterial products. Our study examined if nonpathogenic bacteria or lipopolysaccharide (LPS), can affect epithelial function in the presence of monocytes/macrophages. Lamina propria mononuclear cells (LPMCs) and peripheral blood monocytes (PBMs) were obtained from patients with Crohn's disease and control patients. Filter-grown T84 epithelial monolayers were co-cultured with nonactivated or LPS-activated LPMCs or PBMs for 48 hours. Epithelial secretory [baseline short-circuit current (Isc) and DeltaIsc to forskolin] and barrier (transepithelial electrical resistance) parameters were measured in Ussing chambers. LPS-activated PBMs from both controls and patients with Crohn's disease significantly increased Isc ( approximately 300%) and reduced transepithelial electrical resistance ( approximately 40%). Epithelial function was not altered after co-culture with control LPMCs +/- LPS. However, LPMCs from patients with Crohn's disease spontaneously secreted tumor necrosis factor-alpha, and induced epithelial changes similar to those produced by LPS-activated PBMs. Co-culture with control Escherichia coli and PBMs induced comparable changes in epithelial physiology, which were abrogated by anti-tumor necrosis factor-alpha antibody. We conclude that LPMCs of patients with Crohn's disease are spontaneously activated, possibly by gram-negative luminal bacteria, and can directly cause significant alterations in epithelial ion transport and barrier functions.

Adolescent↗

PubMed2002

Glutamine on the luminal microbial environment after massive small bowel resection.

To evaluate the oral glutamine (GLN) on the luminal microbes and bacterial translocation (BT) in short bowel, 45 Wistar rats were utilized in three groups; A (control), and B and C (short bowel, 85% of small bowel resected). The group A was fed with elemental diet (EmD), B with EmD+2% glycine, and C with EmD+2% GLN. The groups B and C were isocaloric and isonitrogenous. Wet weight, DNA, protein, and histomorphometry of the mucosa and parallel microbial culture from cecal contents, caval blood, and tissue blocks of the liver, spleen, and mesenteric lymph nodes were performed on the 5th, 10th, and 15th day. Mucosal growth was higher in group C than B. Colony forming units (CFU) from cecal contents increased more in group B than in C. BTs in A, B, and C were 7/15, 8/15, and 2/15, respectively. Total CFUs in blood and tissues were 5.8 X 10(4)/g, 5.5 X 10(6)/g, and 1.8 X 10(4)/g, respectively. As for BT, the most frequent organism was Klebsiella in A (79.3%), but E. coli in B and C (94.2% and 55.6%). GLN seems to suppress luminal microbes, and reduces BT in short bowel due to enforced barrier function and proliferation of the mucosa.

Animals↗

PubMed2003

Enteric flora and lymphocyte-derived cytokines determine expression of heat shock proteins in mouse colonic epithelial cells.

BACKGROUND & AIMS: Inducible heat shock proteins (hsps), particularly hsp25 and hsp72, are expressed by surface colonocytes and may have a role in protecting intestinal epithelial cells against injury. This study is aimed at determining if enteric bacteria and/or immune signals regulate their physiologic expression. METHODS: Intestinal hsp25, hsp72, and constitutive hsc73 expression were studied in immunodeficient RAG-1(-/-) mice and in normal mice. Mucosal permeability was measured by mannitol flux and transepithelial resistance. Hsp expression in intestinal YAMC cells was assessed after incubation with recombinant cytokines, activated lamina propria lymphocytes (LPLs), or Bacteroides fragilis. RESULTS: Chronic metronidazole treatment decreases colonic mucosal hsp25 and hsp72 expression, an effect associated with increased susceptibility of mucosal barrier function to C. difficile toxin A. Hsp expression also was increased in YAMC cells incubated with B. fragilis, an effect mediated by lipopolysaccharide and other bacteria-derived factors. Colonic hsp72, but not hsp25 or hsc73, expression is decreased in RAG-1(-/-) mice. Recombinant IL-2 and other cytokines enhance YAMC hsp25 and/or hsp72 expression. Activated LPLs induce YAMC hsp expression, an effect blocked by IL-2 neutralizing antibody. CONCLUSIONS: Enteric flora and mucosal lymphocytes play a role in maintaining physiologic expression of colonocyte hsp25 and hsp72.

Animals↗

PubMed2002

TGF-beta effects on epithelial ion transport and barrier: reduced Cl- secretion blocked by a p38 MAPK inhibitor.

Growth factors affect a variety of epithelial functions. We examined the ability of TGF-beta to modulate epithelial ion transport and permeability. Filter-grown monolayers of human colonic epithelia, T84 and HT-29 cells, were treated with TGF-beta (0.1-100 ng/ml, 15 min-72 h) or infected with an adenoviral vector encoding TGF-beta (Ad-TGF beta) for 144 h. Ion transport (i.e., short-circuit current, I(sc)) and transepithelial resistance (TER) were assessed in Ussing chambers. Neither recombinant TGF-beta nor Ad-TGF beta infection affected baseline I(sc); however, exposure to > or = 1 ng/ml TGF-beta led to a significant (30-50%) reduction in the I(sc) responses to forskolin, vasoactive intestinal peptide, and cholera toxin (agents that evoke Cl(-) secretion via cAMP mobilization) and to the cell-permeant dibutyryl cAMP. Pharmacological analysis of signaling pathways revealed that the inhibition of cAMP-driven epithelial Cl(-) secretion by TGF-beta was blocked by pretreatment with SB-203580, a specific inhibitor of p38 MAPK, but not by inhibitors of JNK, ERK1/2 MAPK, or phosphatidylinositol 3'-kinase. TGF-beta enhanced the barrier function of the treated monolayers by up to threefold as assessed by TER; however, this event was temporally displaced from the altered I(sc) response, being statistically significant only at 72 h posttreatment. Thus, in addition to TGF-beta promotion of epithelial barrier function, we show that this growth factor also reduces responsiveness to cAMP-dependent secretagogues in a chronic manner and speculate that this serves as a braking mechanism to limit secretory enteropathies.

Biological Transport↗

PubMed1996

Structure, function, and regulation of the mammalian facilitative glucose transporter gene family.

The facilitative transport of glucose across the plasma membranes of mammalian cells is catalyzed by a family of glucose transport proteins (GLUT). Four glucose transport proteins and a fructose transport protein have been identified. These transport proteins have unique tissue distributions and biochemical properties under- lying specific physiologic functions. GLUT1, the first GLUT isoform identified, is expressed at highest levels in the endothelial of barrier tissues such as blood vessels and the blood-brain barrier. GLUT2, found predominantly in liver, intestine, kidney, and pancreatic beta-cells, is a low-affinity glucose transport protein that is part of the glucose sensor in pancreatic beta-cells and facilitates either glucose uptake or efflux from the liver depending on the nutritional state. GLUT3 is the glucose transporter responsible for maintaining an adequate glucose supply to neurons. GLUT4 is the insulin-regulated glucose transporter found in adipose tissues, heart muscles, and skeletal muscles that is responsible for insulin-regulated glucose disposal.

Animals↗

PubMed2003

Mucosal repair in the gastrointestinal tract.

OBJECTIVE: The epithelial response to injury in the intestinal mucosa will be described. DESIGN: A comprehensive evaluation of the literature was performed to provide a thorough review of mucosal injury and repair. RESULTS: The intestinal mucosa is a rapidly proliferating sheet of epithelial cells that sustains injury in response to stresses ranging from physiologic daily digestive trauma to severe insults associated with ischemia, chemicals, and infection. Breaks in epithelial continuity impair mucosal barrier function, perturb normal absorptive and secretory transport properties, and render the host susceptible to local infection and distant organ pathology. Minor breaches are rapidly repaired by epithelial restitution, a process independent of cell proliferation. Restitution is regulated by a variety of cytokines and growth factors and is modulated by integrin-dependent interactions with the extracellular matrix. The intracellular mechanisms that control restitution are complex and involve signaling pathways that control dynamic remodeling of the actin cytoskeleton. Emerging understanding of reparative processes suggest several possible therapeutic strategies to enhance gastrointestinal wound healing. CONCLUSION: Minor epithelial injuries are repaired with the complex process of epithelial restitution independent of cell proliferation.

Animals↗

PubMed2006

WAY-202196, a selective estrogen receptor-beta agonist, protects against death in experimental septic shock.

OBJECTIVE: To determine the effect of an estrogen receptor-beta selective agent in experimental models of systemic infection and sepsis. DESIGN: WAY-202196, a nonsteroidal selective estrogen receptor-beta agonist, was tested in the murine listeriosis model, the neutropenic rat Pseudomonas aeruginosa infection, and the mouse cecal ligation and puncture sepsis models. SETTING: University-affiliated biomedical research laboratory. SUBJECTS: BALB/c mice and Sprague-Dawley rats. INTERVENTIONS: WAY-202196 or control (vehicle) was administered orally in doses ranging from 1.5 to 50 mg/kg at various time points in the three experimental model systems. MEASUREMENTS AND MAIN RESULTS: Susceptibility of mice treated with a single oral dose of up to 50 mg/kg WAY-202196 did not differ from those treated with vehicle alone after systemic challenge by Listeria monocytogenes, suggesting a lack of generalized immunosuppression. In the neutropenic rat model, daily administration of WAY-202196 (50 mg/kg) significantly increased survival against an otherwise lethal challenge of P. aeruginosa 12.4.4 compared with the control group (83% vs. 25% survival; p < 0.05). Preservation of intestinal mucosal weight and prevention of histopathologic changes were also observed with the administration of WAY-202196. Similar results were obtained in a cecal ligation and puncture model, in which multiple oral doses of WAY-202196 (50 mg/kg) improved survival (83% vs. 0%; p < 0.05), preserved intestinal epithelial integrity, and significantly reduced systemic bacteremia and peritoneal interleukin-6 and tumor necrosis factor levels. The estrogen receptor-beta agonist provided a comparable level of protection in both male and female animals. CONCLUSION: These results indicate that oral administration of WAY-202196 preserved gastrointestinal barrier function and improved outcome in experimental models of systemic infection and inflammation. WAY-202196 and similar agents may prove useful clinically as a novel treatment strategy for the treatment or prevention of severe sepsis.

Administration, Oral↗

PubMed1991

[The hydrolases of the mucosal, submucosal and muscular layers of the small intestine and their functions].

Proceeding from the newly obtained evidence on the distribution of digestive enzymes in mucosal, submucosal and muscular layers of the small intestine in rats, a hypothesis has been formulated: in addition to the enterocyte enzyme complex forming the epithelial barrier, there seems to exist a postepithelial barrier formed by the enzymes localized in subepithelial structures. The efficiency of this second barrier was manifested by the study of the peptide hydrolysis and transport using everted intact and de-epithelialized intestinal sacs.

Animals↗

PubMed2001

Symposium on 'dietary influences on mucosal immunity'. How dietary antigens access the mucosal immune system.

The intestinal epithelium is a selective barrier where incompletely-digested food antigens are transmitted to the immune system. Food antigens are often the starting point of intestinal diseases such as food allergy or coeliac disease. The intestinal epithelial cells (IEC) take up and process food antigens mainly by fluid-phase transcytosis involving two functional pathways, one minor direct pathway without degradation and another major lysosomal degradative pathway. Among the peptidic metabolites generated during transepithelial transport of luminal antigens, some have a molecular mass compatible with a binding to restriction (major histocompatibility complex; MHC) molecules; the latter can be up regulated on enterocytes, especially in inflammatory conditions. Indeed, interferon-gamma not only increases the paracellular absorption of antigens, but also their transcytosis across epithelial cells. It has been reported that enterocytes may even directly present peptidic epitopes to underlying T-cells. As a new potential way of transmitting peptidic information to the local or systemic immune system, the secretion by IEC of antigen-presenting vesicles called exosomes and bearing MHC-peptide complexes has recently been proposed. Many other factors such as nutritional or environmental factors can also influence the properties of the epithelial barrier and the outcome of the immune response to lumen antigens.

Animals↗

PubMed2003

Migration of Toxoplasma gondii across biological barriers.

The molecular mechanisms underlying migration of pathogens across biological barriers remain poorly characterized. Following oral infection, the apicomplexan parasite Toxoplasma gondii actively crosses non-permissive biological barriers such as the intestine, the blood-brain barrier and the placenta, thereby gaining access to tissues where it causes severe pathology. Recently, enhanced migration was found to be associated with virulent strains of Toxoplasma, suggesting that this phenotype contributes to pathogenesis. The migratory machinery appears to be morphologically and functionally well conserved within the phylum of apicomplexan parasites, however, the mechanisms for cellular traffic to breach biological barriers remain to be elucidated. As penetration of host tissue is a prerequisite for the establishment of infections by most apicomplexan parasites, understanding parasite migration is crucial for the development of new approaches to combat disease.

Actin Cytoskeleton↗

PubMed1991

Maintenance of superior mesenteric arterial perfusion prevents increased intestinal mucosal permeability in endotoxic pigs.

Lipopolysaccharide increases intestinal mucosal permeability to hydrophilic compounds such as chromium 51-labeled edetate (51Cr-EDTA). We sought to determine whether this phenomenon is partly mediated by lipopolysaccharide-induced mesenteric hypoperfusion. We assessed permeability in an isolated segment of ileum by measuring plasma-to-lumen clearances (C) for two probes, 51Cr-EDTA and urea, and expressing the results as a ratio (CEDTA/CUREA). In control pigs (n = 6) resuscitated with Ringer's lactate (RL), mucosal permeability was unchanged during the 210-minute period of observation. In pigs (n = 7) infused with lipopolysaccharide (50 micrograms/kg) and similarly resuscitated with RL, mesenteric perfusion (Qsma) decreased significantly and permeability increased progressively and significantly. When endotoxic pigs (n = 6) were resuscitated with a regimen (RL plus hetastarch plus dobutamine) that preserved normal Qsma, lipopolysaccharide-induced mucosal hyperpermeability was prevented. Resuscitation of endotoxic pigs (n = 6) with RL plus hetastarch provided intermediate protection against both mesenteric hypoperfusion and increased permeability. These data suggest that diminished Qsma contributes to impaired ileal mucosal barrier function in experimental endotoxicosis.

Analysis of Variance↗

PubMed2004

Inhibition of nitric oxide synthesis potentiates the colonic permeability increase triggered by luminal bile acids.

AIM: Experiments were performed in anaesthetized rats to clarify the role of nitric oxide (NO) in the control of colonic permeability. METHODS: Colonic luminal pressure, the transmucosal potential difference (PD) and the clearance of [3H] mannitol and [14C] urea from blood to lumen were measured. NO synthesis was blocked with Nomega-nitro-L-arginine (L-NNA) i.v. and mucosal permeability was increased by deoxycholic acid (DCA, 4 mm). The involvement of histamine in the response was studied by giving the histamine H1 receptor blocker pyrilamine. RESULTS: In proximal colon, L-NNA per se increased luminal pressure and PD but had no significant effect on clearance. DCA per se increased luminal pressure, had no significant effect on PD, but increased mannitol and urea clearance and the clearance ratio. L-NNA and pyrilamine both blocked the luminal pressure effect of DCA but L-NNA had no significant effect on the clearance response to DCA. In distal colon, L-NNA per se had no significant effect on pressure and clearance, but increased PD like in proximal colon. DCA had no significant effect on luminal pressure, but markedly reduced PD and increased both clearance and clearance ratio. In this segment, L-NNA significantly potentiated the clearance response to DCA, and further increased clearance ratio to a value not significantly different from unity (1.00 +/- 0.05). CONCLUSION: The data suggest that in vivo, moderate concentrations of bile acids increase colonic permeability in rats via a mechanism that is inhibited by NO in distal but not in proximal colon. In distal colon, NO may contribute to the maintenance of epithelial barrier function.

Animals↗

PubMed2003

Live probiotics protect intestinal epithelial cells from the effects of infection with enteroinvasive Escherichia coli (EIEC).

BACKGROUND: The colonic epithelium maintains a life long reciprocally beneficial interaction with the colonic microbiota. Disruption is associated with mucosal injury. AIMS: We hypothesised that probiotics may limit epithelial damage induced by enteroinvasive pathogens, and promote restitution. METHODS: Human intestinal epithelial cell lines (HT29/cl.19A and Caco-2) were exposed to enteroinvasive Escherichia coli (EIEC 029:NM), and/or probiotics (Streptococcus thermophilus (ST), ATCC19258, and Lactobacillus acidophilus (LA), ATCC4356). Infected cells and controls were assessed for transepithelial resistance, chloride secretory responses, alterations in cytoskeletal and tight junctional proteins, and responses to epidermal growth factor (EGF) stimulation. RESULTS: Exposure of cell monolayers to live ST/LA, but not to heat inactivated ST/LA, significantly limited adhesion, invasion, and physiological dysfunction induced by EIEC. Antibiotic killed ST/LA reduced adhesion somewhat but were less effective in limiting the consequences of EIEC invasion of cell monolayers. Furthermore, live ST/LA alone increased transepithelial resistance, contrasting markedly with the fall in resistance evoked by EIEC infection, which could also be blocked by live ST/LA. The effect of ST/LA on resistance was accompanied by maintenance (actin, ZO-1) or enhancement (actinin, occludin) of cytoskeletal and tight junctional protein phosphorylation. ST/LA had no effect on chloride secretion by themselves but reversed the increase in basal secretion evoked by EIEC. EIEC also reduced the ability of EGF to activate its receptor, which was reversed by ST/LA. CONCLUSIONS: Live ST/LA interact with intestinal epithelial cells to protect them from the deleterious effect of EIEC via mechanisms that include, but are not limited to, interference with pathogen adhesion and invasion. Probiotics likely also enhance the barrier function of naïve epithelial cells not exposed to any pathogen.

Cell Adhesion↗

PubMed2002

Transporter-mediated Drug Interactions.

Since 1994, researchers have isolated various genes encoding transporter proteins involved in drug uptake into and efflux from tissues that play key roles in the absorption, distribution and secretion of drugs in animals and humans. The pharmacokinetic characteristics of drugs that are substrates for these transporters are expected to be influenced by coadministered drugs that work as inhibitors or enhancers of the transporter function. This review deals with recent progress in molecular and functional research on drug transporters, and then with transporter-mediated drug interactions in absorption and secretion from the intestine, secretion from the kidney and liver, and transport across the blood-brain barrier in humans. Although the participation of the particular transporters in observed drug-drug interactions can be difficult to confirm in humans, this review focuses mainly on pharmacokinetic interactions of clinically important drugs.

Journal Article↗

PubMedDate not supplied

[Intralymphatic drug therapy--a pathogenetically substantiated method of treatment in peritonitis].

The method of endolymphatic drug therapy (EDT) suggested by the authors has some advantages over the method of endoarterial therapy (which has proved to be effective in clinical practice) because it is aimed not only at control of the microbial flora, but also at correction of rheologic and microcirculatory disorders, improvement of the processes of tissue respiration and metabolism, stimulation of the intestine, prevention of the damaging effect of enzymes, toxins, and poisons on the organs and tissues of the body, and at correction of disorders of the immune status with promotion of the barrier function of the lymph nodes and the lymphatic system as a whole. EDT may be recommended for wide use in the clinic in the treatment of patients with peritonitis and other serious surgical infections unresponsive to the generally applied methods of management.

Adjuvants, Immunologic↗