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Results for “Intestinal Barrier Function”

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PubMed1991

Intestinal permeability and bacterial translocation following small bowel transplantation in the rat.

In addition to its role in absorbing nutrients, the intestinal mucosa provides an important barrier against toxins and bacteria in the bowel lumen. The present study evaluated gut barrier function following orthotopic (in continuity) intestinal grafting in rats. Graft histology, intestinal permeability, and bacterial translocation to the grafted mesenteric lymph nodes, the host's liver, and the host's spleen were assessed on the 3rd, 5th, and 7th postoperative days. The study group received no immunosuppression after allotransplantation. The two control groups included rats with isografts and rats with cyclosporine-treated allografts. On the 7th POD, the study animals had moderate transmural inflammation due to rejection, with normal histology in the isografts and CsA-treated allografts; increased intestinal permeability, measured by urinary excretion of oral 51Cr-EDTA (P less than 0.01); and increased number of bacteria in the MLN and spleen (P less than 0.05). The number of bacteria in the MLN and spleen of the study group positively correlated with the changes in intestinal permeability (P less than 0.05). Rejection of the orthotopic intestinal graft leads to increased intestinal permeability and bacterial translocation from the lumen of the graft to the host's reticuloendothelial system. Measures to improve gut barrier function and antibiotic therapy during rejection episodes may help reduce the incidence of septic complications after intestinal grafting.

Animals↗

PubMed2006

Influences of enteral nutrition combined with probiotics on gut microflora and barrier function of rats with abdominal infection.

AIM: To investigate the influences of enteral, parenteral nutrition and probiotics delivered by gut on intestinal microecology, epithelial tight junctions, immune and barrier function of rats with abdominal infection. METHODS: Rat abdominal infection models established with cecal ligation and perforation method, were divided into three groups: parenteral nutrition (PN group, n = 7), PN+enteral nutrition (EN group, n = 7) and PN + EN + probiotics (probiotics group, n = 7) via the needle jejunostomy and neck vein for five days. The total nutritional supplement of the three groups was isonitrogenic and isocaloric. Probiotics was delivered by jejunostomy 10 mL/d (1 x 10(8) cfu/mL). The rats were killed on the sixth day. The feces in the cecum were cultured for anaerobic bacterial growth and analyzed with bacterial group DNA fingerprint profile with random amplified polymorphic DNA. The transmembrane binding proteins (occludin) and IgA level in plasma cells of intestine epithelium in colon and terminal ileum were measured by an immunohistochemistry method. The ultrastructure of intestinal epithelial tight junctions in colon and small intestine was observed by electron-microscopy. Vena cava blood and the homogenated tissue of liver, lung and mesenteric lymph nodes were cultured to determine the bacterial translocations, and endotoxin in the blood from portal vein was detected. RESULTS: (1) The amount of bacteria of gut species in EN group and probiotic group was higher than that in PN group. The DNA-profiles in EN group and probiotic group were similar to that of normal rats. The number of DNA-profiles in probiotics group was much more than that in PN group and EN group. Moreover, there were strange stripes in PN group. (2) The expression of occludin and IgA in the small and large intestine in EN group (2.309 +/- 0.336, 15.440 +/- 2.383) and probiotic group (2.938 +/- 0.515, 16.230 +/- 3.183) was improved as compared with PN group (1.207 +/- 0.587, P < 0.05, 11.189 +/- 2.108, P < 0.01). The expression of occludin in probiotic group (intestine: 2.93 +/- 0.515; cecum: 3.40 +/- 0.617) was higher than that in EN group (intestine: 2.309 +/- 0.336; cecum: 2.076 +/- 0.670; P < 0.05). The expression of IgA, especially in EN group (intestine: 15.440 +/- 2.383) and probiotic EN group (large intestine: 12.516 +/- 1.542) significantly increased as compared with PN group (intestine: 11.189 +/- 2.108; cecum: 10.160 +/- 1.643; P<0.01). The intestinal epithelial tight junctions and microvilli of the probiotic group were more intact than those in the PN group. (3) The bacterial translocations in blood, liver, lung and mesenteric lymph nodes, and the levels of endotoxin were significantly reduced in probiotic (0.082 +/- 0.029) and EN (0.125 +/- 0.040) groups as compared with PN group (0.403 +/- 0.181, P < 0.05). CONCLUSION: Application of EN combined with probiotics could improve the expression of transmembrane binding proteins (occludin) and IgA, correct the intestinal flora disturbance, maintain gut barrier functions and tight junctions, and reduce the occurrence of gut bacterial translocation.

Abdomen↗

PubMed2004

The female intestine is more resistant than the male intestine to gut injury and inflammation when subjected to conditions associated with shock states.

Having documented that proestrus female rats are more resistant to shock-induced acute gut and hence lung injury than male rats, we tested the hypothesis that the female gut is more resistant to injury and produces less of an inflammatory response than the male gut when exposed to conditions associated with shock states (hypoxia and acidosis) utilizing the ex vivo Ussing chamber system. Ileal mucosal membranes harvested from normal male and female rats mounted in Ussing chamber systems were exposed to normoxia or 40 min of hypoxia at a normal pH (pH 7.3) or acidosis (pH 6.8). Cytokine and nitric oxide levels in the serosal compartment of the Ussing chamber were measured at the end of the 3-h experimental period to assess the immunoinflammatory response, whereas FITC-dextran (mol wt 4,300) was employed to assess barrier function. Histomorphological changes were used to quantitate gut mucosal injury. Hypoxia, acidosis, or hypoxia plus acidosis was associated with a significant increase in proinflammatory cytokine production [interleukin (IL)-6, tumor necrosis factor, and macrophage inflammatory protein (MIP)-2] by the male compared with the female intestinal segments. In contrast, the female gut manifested a higher anti-inflammatory response (nitric oxide and IL-10) and improved intestinal barrier function as well as less evidence of mucosal injury than the male intestinal segments. Administration of estradiol or the testosterone receptor antagonist, flutamide, to male rats abrogated the increase in gut injury and the increased IL-6 and MIP-2 response observed after hypoxia plus acidosis. These results suggest that gender differences in the ex vivo intestinal response to stresses, such as hypoxia and acidosis, exist and that the administration of estradiol or blockade of the testosterone receptor to male rats mitigates these gender differences.

Acidosis↗

PubMed2005

Ethanol-induced CXC-chemokine synthesis and barrier dysfunction in intestinal epithelial cells.

BACKGROUND: Ethanol exposure contributes to infectious complications in burn and trauma patients through a process known as "bacterial translocation." Two major factors, 1) physical disruption of the intestinal mucosal barrier and 2) suppression of immune defense, explain this phenomenon. However, little information is available concerning the immune mechanisms of ethanol-induced bacterial translocation. In this study we investigated the effect of physiological concentrations of ethanol on immune function, especially on CXC-chemokine secretion, neutrophil migration, and barrier function in the small intestine METHODS: A rat small intestinal intestinal cell line (IEC-18 cells) was exposed to 50-500 mM ethanol for 24 hr with or without IL-1 beta. Secretion of CXC chemokines (GRO/CINC-1 and MIP-2) was measured by ELISA assay, and barrier dysfunction was assessed by the apical-to-basolateral flux of HRP-dextran. Neutrophil transmigration was assessed by enzyme histochemistry (AS-D chloroesterase staining) RESULTS: Exposure to ethanol concentrations of 200 mM and over increased GRO/CINC-1 secretion, and MIP-2 secretion increased at 500 mM. Administration of ethanol in combination with IL-1 beta had no additive effect on the release of GRO/CINC-1 and MIP-2. Exposure of IEC-18 monolayers to ethanol resulted in a dose-dependent increase in permeability but IL-1 beta had no effect on barrier function. Ethanol had no effect on neutrophil migration in enzyme histochemistry analysis CONCLUSIONS: The above observations suggest that ethanol induced physical disruption of the intestine but not neutrophil transmigration is the main cause of the bacterial translocation that leads to bacteremia and endotoxemia in alcoholics.

Alcoholic Intoxication↗

PubMed2002

Immunological effects of yogurt addition to a re-nutrition diet in a malnutrition experimental model.

The therapeutic and preventive effects of yogurt and lactic acid bacteria on diseases such as cancer, infection and gastrointestinal disorders are well ocumented. The aim of this research was to study the effects of different doses of yogurt addition after milk re-nutrition diet, on the recovery of the intestinal barrier and mucosal immune function. Experiments were performed on groups of mice, malnourished and re-nourished with milk during 7 d, and mice with diet supplemented with yogurt for 2, 5 and 7 consecutive d. Nutritional parameters such as weight gain, serum total protein, and the number of IgA, IgM and IgG B cells of the small intestine were determined. We also quantified intraepithelial leukocytes, mastocytes and goblet cells, and performed structural and ultrastructural studies on the small intestine. We observed that 5 d of yogurt feeding was the optimal dose for improving gut barrier function and mucosal immune system in a malnutrition model. This effect was not observed with milk re-nutrition. Although the results were better for 5 d of yogurt, addition for 7 d also showed beneficial effects. Yogurt feeding in our model did not impair any gut functions. These results suggest that yogurt addition after a re-nutrition diet gives better recovery of intestinal function than the re-nutrition diet usually recommended. Although these results were obtained in an animal model, they indicate that consumption of yogurt by malnourished children might accelerate the restoration of gut function.

Animals↗

PubMed1997

Dopamine and intestinal mucosal tissue oxygenation in a porcine model of haemorrhage.

Haemorrhage is associated with intestinal mucosal hypoxia and impaired gut barrier function. Dopamine increases oxygen delivery to the intestinal mucosa and may thus counteract haemorrhage-induced mucosal hypoxia. Jejunal mucosal tissue oxygen tension (mucosal PO2) and jejunal oxygen saturation of mucosal microvascular haemoglobin (mucosal HbO2) were measured in 14 anaesthetized pigs. Seven animals served as controls (group C) and seven received continuous infusion of dopamine 16 micrograms kg-1 min-1 (group D) while 45% of blood volume was removed in three equal increments. Resuscitation was performed using shed blood and fluid. Mean arterial pressure and systemic oxygen delivery decreasing significantly during haemorrhage and returned to baseline after resuscitation in both groups. Mucosal PO2 decreased from 4.4 to 1.7 kPa after haemorrhage (P < 0.01) and further to 1.5 kPa after resuscitation (P < 0.01) in group C whereas group D showed an increase from 3.9 to 5.9 kPa after the start of the dopamine infusion (P < 0.05), but no significant difference from baseline after haemorrhage (2.3 kPa) (ns) or resuscitation (3.1 kPa) (ns). Mucosal HbO2 decreased from 52 to 32% after haemorrhage (P < 0.05) and increased to near baseline (37%) (ns) after resuscitation in group C whereas group D showed no significant changes from baseline (54%) throughout the experiment. Comparison between groups showed higher mucosal PO2 and HbO2 values for group D animals after the start of the dopamine infusion (P < 0.05 each), after the first two steps of haemorrhage (P < 0.01 each) and after resuscitation (P < 0.05 each). We conclude that i.v. dopamine 16 micrograms kg-1 min-1 improved tissue oxygenation of the small intestinal mucosa during moderate haemorrhage and subsequent resuscitation.

Animals↗

PubMed1994

Peritonitis impairs intestinal absorption of proline and leucine in the rat.

Systemic sepsis is associated with reduced mesenteric blood flow and impairment of metabolic and barrier functions of the small intestine. A study was performed in the rat to investigate the effect of sepsis induced by caecal ligation and double puncture on intestinal absorption of leucine and proline in vivo. Absorption was studied 24 h after caecal ligation and puncture by measuring intestinal disappearance and circulatory appearance of intraluminal 3H-labelled amino acid over a 60-min study period. Peritonitis resulted in a significant increase relative to controls in the mean (s.e.m.) percentage of leucine (67.2(3.6) versus 18.0(3.5), P < 0.001) and proline (64.7(6.0) versus 15.1(3.7), P < 0.001) remaining within the small intestine. There were significant decreases in portal venous and femoral arterial concentrations of leucine and proline in animals with sepsis. Intestinal amino acid absorption is impaired in this model.

Animals↗

PubMed1996

Active secretion of drugs from the small intestinal epithelium in rats by P-glycoprotein functioning as an absorption barrier.

Because the significance of P-glycoprotein in the in-vivo secretion of beta-blockers in intestinal epithelial cells is unclear, the secretory mechanism for beta-blockers and other drugs has been evaluated. Uptake of the beta-blockers acebutolol, celiprolol, nadolol and timolol, and the antiarrhythmic agent, quinidine by the multidrug-resistant leukaemic cell line variant K562/ADM was significantly lower than that by drug-sensitive K562 cells, suggesting that these beta-blockers are transported by P-glycoprotein out of cells. The reduced uptake of acebutolol by the drug-resistant K562/ADM cells was reversed by treating the cells with anti-P-glycoprotein monoclonal antibody, MRK16, whereas no such alteration in uptake was observed for drug-sensitive K562 cells. Acebutolol uptake by K562/ADM cells was, moreover, markedly enhanced, in a concentration-dependent manner, in the presence of the specific P-glycoprotein inhibitors, MS-209 and cyclosporin. Caco-2 cells were used for evaluation of the role of P-glycoprotein in intestinal permeability to drugs in-vitro. Basolateral-to-apical transport of acebutolol was twice that in the reverse direction. A similar polarized flux was also observed in the transport of vinblastine, but not in that of acetamide or mannitol. When in-vivo intestinal absorption was evaluated by the rat jejunal loop method, with simultaneous intravenous administration of a P-glycoprotein inhibitor, cyclosporin, intestinal absorption of both acebutolol and vinblastine increased 2.6- and 2.2-fold, respectively, but no such enhancement was observed in the absorption of acetamide. The effect of cyclosporin on the intestinal absorption of several drugs was further examined, and the extent of the contribution of P-glycoprotein as an absorption barrier to those drugs was evaluated. ATP depletion by occlusion of the superior mesenteric artery resulted in a clear increase in epithelial permeability to vinblastine, but not to 3-O-methylglucose or acetamide, indicating that vinblastine is secreted by ATP-dependent P-glycoprotein into the lumen. These findings demonstrate that P-glycoprotein plays a role as an absorption barrier by transporting several drugs from intestinal cells into the lumen.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2026

From immature to mature epithelium: unveiling structural dynamics and transcriptional programs in rainbow trout intestinal barrier.

The intestinal epithelium is crucial for nutrient absorption, immune defense, and barrier function in farmed fish. However, the molecular mechanisms underlying its development and maturation in salmonids remain poorly characterized, hindering our ability to address pervasive gut health challenges in aquaculture. In this study, we use the RTgutGC cell line to implement an epithelial maturation model with the aim of characterizing the global transcriptional program in rainbow trout (Oncorhynchus mykiss). We evaluated in vitro culture conditions to generate a polarized epithelial barrier with high transepithelial electrical resistance (TEER = 75.8 Ω × cm2), low permeability (6.2 × 10-6 cm/s), and well-defined apical specializations, including microvilli-like structures and clusters of these structures (brush border). Comparative transcriptomic profiling between immature (7 days post-seeding, dps) and mature (28 dps) epithelia revealed 3,817 differentially expressed genes (DEGs). Functional enrichment analysis showed that maturation was characterized by the downregulation of proliferative and ribosomal pathways and the concerted upregulation of processes critical for barrier function, including transmembrane transport, proteolysis, cell adhesion, extracellular matrix organization, and tight junction assembly. We identified a core set of 60 genes indicators of epithelial maturation, encompassing solute transporters (slc26a6, slc43a2), tight junction proteins (tjp1, cldn1, cldn3, cldn5, cldn18, among others), and structural components essential for microvilli formation and polarization (cdhr5b, pard6a). By integrating ultrastructural, functional, and transcriptomic data, this study established a framework for future mechanistic investigations into gut development and maturation in vitro. This set of mature epithelium indicators has diverse applications, such as the design of nutritional and pharmacological interventions to improve gut health and resilience in farmed fish.

Animals↗

PubMed1998

Phenotypic and functional characteristics of intestinal intraepithelial lymphocytes during acute rejection of small intestinal allografts.

Infiltration of a transplanted organ by host lymphoid cells is the hallmark of acute rejection. However, after intestinal transplantation, physiological lymphocyte migration may lead to host cell infiltration of the graft even in the absence of rejection. It is unclear whether this lymphocyte migration also involves the intraepithelial compartment of the graft or whether infiltration there is indicative of acute rejection. We demonstrate here that host cell infiltration of the intestinal mucosa occurs both during acute rejection of a small bowel allograft and, to a lesser extent, when rejection is prevented by immunosuppression with FK506. The infiltrating host cells consisted of CD3+ T cells with a predominant CD4-CD8+ phenotype resembling intraepithelial lymphocytes (IELs). Functional studies showed that the nonspecific cytolytic activity of IELs was not affected by acute rejection or by immunosuppression with FK506. These findings indicate that host cell infiltration of the intestinal mucosa does not connote an ongoing acute rejection. Furthermore, the decreased mucosal barrier function during acute rejection of intestinal allgrafts is probably not due to impaired cytolytic activity of IELs.

Animals↗

PubMed2000

Eicosanoids and the small intestine.

Prostaglandins play an important role in modulation of various physiologic processes in the small intestine. In this review, the involvement of prostaglandins in various small-intestinal functions including small-intestinal secretion, mucosal protection, epithelial and endothelial barrier function, and motility are discussed.

Animals↗

PubMed1999

Changes in intestinal absorption of 5-fluorouracil-treated rats.

5-Fluorouracil chemotherapy is often accompanied by gastrointestinal toxicity. In this study, we investigated the effect of 5-fluorouracil on the epithelial barrier function of rat small intestine by examining the absorption of a poorly absorbable marker, fluorescein isothiocyanate-labelled dextran (molecular weight 4,400). We further evaluated the intestinal absorption of 5-fluorouracil in rats treated orally with 5-fluorouracil once daily for 4 days. The small intestinal absorption of fluorescein isothiocyanate-labelled dextran and 5-fluorouracil was tested using in situ closed loop intestine technique and in vitro everted intestine technique, respectively. After administration of 5-fluorouracil to rats for 4 days, the body weight of rats decreased significantly and the fluorescein isothiocyanate-labelled dextran concentration in plasma increased significantly, compared with that of control rats to which the saline solution alone was administered. Moreover, the intestinal absorption of 5-fluorouracil in the 5-fluorouracil-treated rats was enhanced significantly, compared with that of control rats. The administration of 5-fluorouracil to rats caused body weight loss and epithelial barrier dysfunction of the small intestine in rats as shown by the increased permeation of the high molecular weight compound, fluorescein isothiocyanate-labelled dextran. The increased absorption of 5-fluorouracil after this treatment suggest that the 5-fluorouracil toxicity might be amplified by its treatment.

Animals↗

PubMed2004

Endothelin-3 induced mesenteric vasoconstriction and PMN infiltration in the rat small intestine: role of endothelin receptors.

The objectives of this study were to characterize endothelin (ET)-3-induced alterations in intestinal hemodynamics and to evaluate whether ET-3 administration alters the tissue levels of polymorphonuclear leukocytes (PMNs) and modulates the epithelial barrier function of the small intestine. ET-3 (100 pmol/kg/min) was infused into the superior mesenteric artery (SMA) for 10 min, and tissue samples were obtained 30 min after terminating the infusion. SMA blood flow was significantly decreased throughout the experiment following ET-3 infusion. Pretreatment with bosentan (ET-A and ET-B receptor antagonist), ET-B receptor antagonist BQ-788 or ET-A receptor antagonist BQ-485 completely inhibited the ET-3-induced decrease in the SMA blood flow. Similar results were obtained from the resistance data, in which ET-3-induced increases in SMA resistance were significantly reduced by all ET receptor antagonists. ET-3 administration significantly elevated tissue MPO activity, blood-to-lumen clearance of (51)Cr-EDTA and caused a marked microscopic damage in the intestinal mucosa. ET-3-induced elevations in tissue PMN infiltration and mucosal damage were significantly inhibited by pretreatments with ET-A or ET-B receptor antagonists. Overall, our data indicate that ET-3 causes microscopic damage, PMN infiltration and mucosal dysfunction in the rat small intestine. In addition, ET-3-induced hemodynamic alterations as well as tissue PMN infiltration and mucosal damage are mediated by both ET-A and ET-B receptors.

Animals↗

PubMed2006

Luminal leptin activates mucin-secreting goblet cells in the large bowel.

Leptin has been suggested to be involved in tissue injury and/or mucosal defence mechanisms. Here, we studied the effects of leptin on colonic mucus secretion and rat mucin 2 (rMuc2) expression. Wistar rats and ob/ob mice were used. Secretion of mucus was followed in vivo in the rat perfused colon model. Mucus secretion was quantified by ELISA, and rMuc2 mRNA levels were quantified by real-time RT PCR. The effects of leptin alone or in association with protein kinase C (PKC) and phosphatidylinositol 3-kinase (PI3K) inhibitors on mucin secreted by human mucus-secreting HT29-MTX cells were determined. Leptin was detected in the rat colonic lumen at substantial levels. Luminal perfusion of leptin stimulates mucus-secreting goblet cells in a dose-dependent manner in vivo in the rat. Leptin (10 nmol/l) increased mucus secretion by a factor of 3.5 and doubled rMuc2 mRNA levels in the colonic mucosa. There was no damage to mucosa 24 h after leptin, but the number of stained mucus cells significantly increased. Leptin-deficient ob/ob mice have abnormally dense mucus-filled goblet cells. In human colonic goblet-like HT29-MTX cells expressing leptin receptors, leptin increased mucin secretion by activating PKC- and PI3K-dependent pathways. This is the first demonstration that leptin, acting from the luminal side, controls the function of mucus-secreting goblet cells. Because the gel layer formed by mucus at the surface of the intestinal epithelium has a barrier function, our data may be relevant physiologically in defence mechanisms of the gastrointestinal tract.

Animals↗

PubMed1988

Clostridium difficile toxin A perturbs cytoskeletal structure and tight junction permeability of cultured human intestinal epithelial monolayers.

Toxin A of Clostridium difficile causes severe inflammatory enterocolitis in man and animals that appears to be mediated in part by acute inflammatory cells that migrate into the toxin A-exposed mucosa. To determine the direct effects of toxin A on intestinal epithelial permeability and structure in the absence of other modulating factors, we used cultured monolayers of a human intestinal epithelial cell line (T84). A toxin A concentration of 7 x 10(-1) micrograms/ml (3 x 10(-9) M) nearly abolished monolayer transepithelial resistance within 6-8 h. This marked permeability defect occurred while the monolayers were still confluent. Dual sodium-mannitol flux studies localized the permeability defect to the intercellular tight junction. Cytotoxicity assays and morphological evaluation using Nomarski optics and electron microscopy failed to demonstrate any evidence of cell damage at the time the maximum resistance response was observed. Fluorescent staining for F actin, however, revealed a marked decrease in fluorescent intensity in toxin-treated monolayers versus controls. These data show that toxin A can directly affect the barrier function of this model intestinal epithelium and initially does so by selectively enhancing tight junction permeability. Furthermore, cytoskeletal structure is markedly altered over the same time course, although the integrity of individual cells is maintained. Because the cytoskeleton of intestinal epithelial cells is known to be capable of regulating tight junction permeability, we speculate that the above effects of toxin A on epithelial barrier function result from alterations of the cytoskeleton.

Animals↗

PubMed1992

Intestinal permeability in pediatric gastroenterology.

The role of the physiologic barrier function of the small bowel and its possible role in health and disease has attracted much attention over the past decade. The intestinal mucosal barrier for luminal macromolecules and microorganism is the result of non-immunologic and immunologic defense mechanisms. The non-immunologic mechanisms consist of intraluminal factors such as gastric acid, proteolytic activity, and motility and of mucosal surface factors like mucin and the microvillous membrane. The immunologic mechanisms include secretary IgA and cell-mediated immunity. Both types of mechanism are not completely mature at birth. Maturation of this barrier is not finished before the 2nd year of life. One of the aspects of the mucosal barrier function can be estimated by the intestinal permeability (IP) for macromolecules. We use the differential sugar absorption test (SAT), in which the ratio of urinary excretion of a relatively large molecule, lactulose, is compared with that of a relatively small molecule, mannitol, after oral ingestion. Although the small intestine is permeable to certain macromolecules in normal developmental conditions, an increased IP could be involved in the pathophysiology of several diseases, including infectious diarrhea, food allergy, celiac disease, and Crohn's disease. It can be concluded that IP, as measured with the SAT, reflects the state of the mucosal barrier and is altered in several gastrointestinal diseases. The SAT is a non-invasive IP test that can be of diagnostic help to demonstrate alterations in the small-mucosal barrier function and may be useful to evaluate therapeutic interventions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2001

Molecular analysis of commensal host-microbial relationships in the intestine.

Human beings contain complex societies of indigenous microbes, yet little is known about how resident bacteria shape our physiology. We colonized germ-free mice with Bacteroides thetaiotaomicron, a prominent component of the normal mouse and human intestinal microflora. Global intestinal transcriptional responses to colonization were observed with DNA microarrays, and the cellular origins of selected responses were established by laser-capture microdissection. The results reveal that this commensal bacterium modulates expression of genes involved in several important intestinal functions, including nutrient absorption, mucosal barrier fortification, xenobiotic metabolism, angiogenesis, and postnatal intestinal maturation. These findings provide perspectives about the essential nature of the interactions between resident microorganisms and their hosts.

Animals↗

PubMed2001

Interleukin 2 modulates ion secretion and cell proliferation in cultured human small intestinal enterocytes.

AIMS: To determine if interleukin 2 (IL-2) alters epithelial transport and barrier function in cultured human small intestinal enterocytes. METHODS: Confluent monolayers of small intestinal cells derived from duodenal biopsies were treated with IL-2 0.2-50 U/ml for 24 hours prior to study. Transport measurements were performed under short circuited conditions in Ussing chambers, with and without the secretagogues forskolin and 3-isobutyl-1-methyl xanthine (IBMX). Serosal to mucosal flux of 3[H] mannitol (permeability) and 3[H] thymidine uptake (proliferation) were measured. IL-2 receptor and cystic fibrosis transmembrane conductance regulator (CFTR) mRNA were identified using reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: IL-2 did not alter baseline electrical parameters but caused a significant increase in cAMP dependent chloride secretion. The effect was mediated by the IL-2 receptor and paralleled a rapid increase in tyrosine phosphorylation, janus kinase 1, and signal transducers and activators of transcription (STATs) 1, 3, and 5. IL-2 significantly increased proliferation but at a lower dose than observed for enhanced secretion but did not alter permeability. IL-2 receptor beta and gammac chains and CFTR mRNA were identified by RT-PCR. CONCLUSIONS: IL-2 treatment enhances cAMP stimulated chloride secretion and cellular proliferation in a human small intestinal cell line expressing a functional IL-2 receptor.

Analysis of Variance↗