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Results for “Intestinal Barrier Function”

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PubMed2002

PKC-zeta is required in EGF protection of microtubules and intestinal barrier integrity against oxidant injury.

Using monolayers of human intestinal (Caco-2) cells, we showed that epidermal growth factor (EGF) protects intestinal barrier integrity against oxidant injury by protecting the microtubules and that protein kinase C (PKC) is required. Because atypical PKC-zeta isoform is abundant in wild-type (WT) Caco-2 cells, we hypothesized that PKC-zeta mediates, at least in part, EGF protection. Intestinal cells (Caco-2 or HT-29) were transfected to stably over- or underexpress PKC-zeta. These clones were preincubated with low or high doses of EGF or a PKC activator [1-oleoyl-2-acetyl-sn-glycerol (OAG)] before oxidant (0.5 mM H(2)O(2)). Relative to WT cells exposed to oxidant, only monolayers of transfected cells overexpressing PKC-zeta (2.9-fold) were protected against oxidant injury as indicated by increases in polymerized tubulin and decreases in monomeric tubulin, enhancement of architectural stability of the microtubule cytoskeleton, and increases in monolayer barrier integrity toward control levels (62% less leakiness). Overexpression-induced protection was OAG independent and even EGF independent, but EGF significantly potentiated PKC-zeta protection. Most overexpressed PKC-zeta (92%) resided in membrane and cytoskeletal fractions, indicating constitutive activation of PKC-zeta. Stably inhibiting PKC-zeta expression (95%) with antisense transfection substantially attenuated EGF protection as demonstrated by reduced tubulin assembly and increased microtubule disassembly, disruption of the microtubule cytoskeleton, and loss of monolayer barrier integrity. We conclude that 1) activation of PKC-zeta is necessary for EGF-induced protection, 2) PKC-zeta appears to be an endogenous stabilizer of the microtubule cytoskeleton and of intestinal barrier function against oxidative injury, and 3) we have identified a novel biological function (protection) among the atypical isoforms of PKC.

Caco-2 Cells↗

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↗

PubMedDate not supplied

Early increase in intestinal permeability in patients with severe acute pancreatitis: correlation with endotoxemia, organ failure, and mortality.

Sepsis accounts for 80% of deaths from acute pancreatitis. This study aimed to investigate early changes in intestinal permeability in patients with acute pancreatitis, and to correlate these changes with subsequent disease severity and endotoxemia. The renal excretion of enterally administered polyethylene glycol (PEG) 3350 and PEG 400 was measured within 72 hours of onset of acute pancreatitis to determine intestinal permeability. Severity was assessed on the basis of APACHE II scores and C-reactive protein measurements. Serum endotoxin and antiendotoxin antibodies were measured on admission. Eight-five patients with acute pancreatitis (mild in 56, severe in 29) and 25 healthy control subjects were studied. Urinary excretion of PEG 3350 (median) was significantly greater in patients who had severe attacks (0.61%) compared to those with mild disease (0.09%) and health control subjects (0.12%) (P <0. 0001), as was the permeability index (PEG 3350/400 excretion) (P <0. 00001). The permeability index was significantly greater in patients who subsequently developed multiple organ system failure and/or died compared with other severe cases (0.16 vs. 0.04) (P = 0.0005). The excretion of PEG 3350 correlated strongly with endotoxemia (r = 0.8; P = 0.002). Early increased intestinal permeability may play an important role in the pathophysiology of severe acute pancreatitis. Therapies that aim to restore intestinal barrier function may improve outcome.

APACHE↗

PubMed2005

Past and current theories of etiology of IBD: toothpaste, worms, and refrigerators.

While tremendous advances have improved the understanding of inflammatory bowel disease, with regard to environmental risk factors as well as the biochemical nature of the inflammatory process, a determination of primary etiology remains elusive. Numerous theories have been proposed in the past century concerning the cause of Crohn's disease and ulcerative colitis with implications for specific therapies. On further study, most of these ideas and therapies have failed to be accurate in theory or therapeutic approach. Others remain untested or are the focus of current investigation and controversy. This paper reviews the dominant theories of primary etiology. These hypotheses include infectious causes such as Mycobacteria paratuberculosis and measles. Allergic and nutritionally related causes have been the focus of considerable research. Microparticles, which is part of the concept behind toothpaste as a cause, have been suggested more broadly to be the principal factor initiating Crohn's disease. Several of these concepts rely on the idea that there is an increased intestinal permeability that is the central defect leading to Crohn's disease. Rather than being an excessive T cell driven process, Crohn's has been suggested to be an innate immune deficiency, leading to the use of colony stimulating factors to augment the intestinal barrier function and innate immunity. A variety of changes in the gut flora, ranging from a basic dysbiosis to the absence of helminths, have been proposed as the root cause of inflammatory bowel disease.

Colitis, Ulcerative↗

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↗

PubMed1993

Ischemia-reperfusion in feline small intestine: a role for nitric oxide.

The objective of this study was to assess whether nitric oxide synthesis inhibition affects intestinal barrier function after ischemia-reperfusion of the feline small bowel. Local intra-arterial infusion of the nitric oxide synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 25 nmol.ml-1.min-1) was performed in autoperfused segments of cat ileum for 60 min after 90 min of ischemia and 60 min of reperfusion. Epithelial permeability was quantitated by measuring blood-to-lumen clearance of 51Cr-labeled EDTA, and microvascular dysfunction was assessed by measuring the clearance of protein from the vasculature into the interstitium. 125I-labeled albumin clearance from blood to lumen and histology were performed to further characterize the extent of intestinal dysfunction after reperfusion of the postischemic intestine in the presence and absence of L-NAME. Ischemia-reperfusion-induced mucosal and microvascular permeability increases were dramatically augmented by L-NAME infusion, and this effect was reversed by infusion of L-arginine (125 nmol.ml-1.min-1). Initiating L-arginine (but not D-arginine) infusion alone 10 min before reperfusion provided protection against ischemia-reperfusion-induced mucosal barrier dysfunction; however, this was not associated with a reduction in endogenous levels of L-arginine during ischemia-reperfusion. These data suggest that basal nitric oxide production is important in minimizing mucosal and microvascular barrier dysfunction associated with reperfusion of postischemic intestine.

Animals↗

PubMed2006

Stimulation of immunity without alteration of oral tolerance in mice fed with heat-treated fermented infant formula.

OBJECTIVES: Little information is available on the properties of fermented milk formula intended to healthy infants. This study analyzes the effect of long-term ingestion of a heat-treated, fermented milk formula on the development of oral tolerance or systemic immune response to soluble antigens in mice. MATERIALS AND METHODS: The C3H/HeN mice, fed with a heat-treated fermented (Bifidobacterium breve C50 and Streptococcus thermophilus 065) infant formula (htFF) or a matched control diet (control), were immunized with ovalbumin (OVA) with or without gavage of 20 mg OVA to induce tolerance or immunity, respectively. Systemic and local anti-OVA immune responses and intestinal barrier function were measured after 5 to 6 weeks. RESULTS: Oral tolerance to OVA developed similarly in htFF- and control-fed mice, attested to by the downregulation of OVA-specific immunoglobulin (Ig) G and IgE after oral OVA administration. In contrast, immunization with OVA led to significantly higher titers in htFF-fed mice than in control-fed mice (log2 IgG titers, 16.45 +/- 1.24 and 15.46 +/- 0.79, respectively; P = 0.012). Jejunal interferon gamma, interleukin 12p40 and interleukin 10 expressions were significantly higher in tolerized mice fed with htFF compared with those fed with the control diet. Mucosal to serosal intact horseradish peroxidase fluxes were lower in htFF-fed mice than in control-fed mice (39 +/- 8 and 118 +/- 38 ng/h x cm2, respectively; P < 0.0001), indicating that the htFF diet reinforces intestinal barrier capacity to macromolecules. CONCLUSIONS: In mice, htFF strengthens intestinal barrier and enhances systemic immune responses to antigens without interfering with the development of oral tolerance, suggesting a potential beneficial effect in host defence and vaccination.

Administration, Oral↗

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↗

PubMed2001

The gut mucosa barrier is preserved during allogeneic, haemopoietic stem cell transplantation with reduced intensity conditioning.

The efficacy of allogeneic, haemopoietic stem cell transplantation (HSCT) is limited by concomitant toxicity. This has led to the development of less toxic, reduced intensity conditioning (RIC) protocols, whose therapeutic benefit is largely related to an associated, immunity-mediated graft-versus-malignancy effect rather than by the cytotoxic treatment itself. Murine HSCT models suggests that acute graft-versus-host disease (GVHD) increases with the intensification of the conditioning regimen mediated by loss of integrity of the gut mucosa barrier. The present study was undertaken to investigate gastro-intestinal (GI) permeability during allogeneic HSCT with RIC. In 17 patients (myeloablative conditioning in nine, RIC in eight), intestinal permeability was assessed by a (51)Cr-EDTA absorption test before the start of cytotoxic treatment the day before stem cell infusion (day -1) and 4, 7 and 14 days after stem cell infusion. Patients receiving RIC did not develop any significant increase in intestinal permeability during the transplantation course but in myeloablatively conditioned patients there was a significant increase in intestinal permeability the day before the stem cell infusion (P < 0.005), on day 4 (P < 0.005), on day 7 (P < 0.01) and on day 14 (P < 0.005) after stem cell infusion, compared with the baseline. Myeloablative conditioning also revealed increased intestinal permeability on day 7 compared with the RIC (P < 0.05). The finding of preserved intestinal-barrier function during allogeneic HSCT with RIC is discussed, with reference to the hypothesis that GI tract damage may be an important initiating event of GVHD.

Adult↗

PubMed2003

The mycotoxin fumonisin B1 alters the proliferation and the barrier function of porcine intestinal epithelial cells.

Fumonisin B1 (FB1) is a mycotoxin produced by Fusarium verticillioides (formerly F. moniliforme), a fungus that commonly contaminates maize. FB1 causes toxicological effects in laboratory and domestic animals including pigs. Because the gastrointestinal tract represents the first barrier met by exogenous food compounds, the purpose of this study was to investigate the effects of FB1 on IPEC-1, a porcine intestinal epithelial cell line. We first verified that low concentrations of FB1 did not exert any cytotoxic effect on IPEC-1. Indeed, significant LDH release was only observed for FB1 concentrations greater than 50 and 700 microM on proliferating and nonproliferating cells, respectively. We then demonstrated that FB1 inhibits proliferation of IPEC-1. Fluorescence-activated cell sorting (FACS) analysis of the cell cycle indicated that FB1 blocks the proliferation of intestinal cells in the G0/G1 phase. Similar results were obtained with LLC-PK1, a renal porcine epithelial cell line, which is considered to be a good model for studying FB1 in vitro effects. We have also assessed the effects of FB1 on the integrity of the barrier formed by the intestinal epithelium. We demonstrated that FB1 decreases the transepithelial electrical resistance (TEER) of IPEC-1 in a time- and dose-dependent manner. This effect was only noticed after a long exposure (8-12 days of treatment). FB1 induced the TEER decrease independently of the cell differentiation stage, and this effect was partially reversible. Taken together, our data indicate that FB1 alters the proliferation and the barrier function of intestinal cells. These results may have implications for humans and animals consuming FB1-contaminated food or feed.

Animals↗

PubMed2003

Gut in diseases: physiological elements and their clinical significance.

The intestinal barrier function of GI tract is very important in the body except for the function of digestion and absorption. The functional status of gut barrier basically reflects the stress severity when body suffers from trauma and various stimulations. Many harmful factors such as drugs, illnesses, trauma and burns can damage the gut barrier, which can lead to the barrier dysfunction and bacterial/endotoxin translocation. The paper discusses and reviews the concepts, anatomy, pathophysiology of gut barrier and its clinical relations.

Animals↗

PubMed1990

The route of feeding influences injury responses.

The balance of current clinical data suggests that the route by which patients are fed during the postinjury phase may influence immunologic and metabolic responses to subsequent insults. The mechanisms underlying such amplification processes are presumed to be generated by loss of intestinal barrier function. The resulting host exposure to toxins is hypothesized to induce regional production of inflammatory mediators which serve to alter organ-specific and systemic responses. The cytokine class of mediators appears capable of altering splanchnic tissue function in a manner consistent with observed clinical responses. The breadth of tissue activity influenced by the cytokines spans those benefitting tissue homeostasis and repair to an exaggerated response which may induce tissue injury and organ failure. Data are presented from both clinical and experimental studies to suggest that a lack of intestinal nutrient provision, such as that induced by parenteral feeding, appears to predispose to enhanced cytokine mediator production in hepatic tissues. Thus alterations in the route of antecedent feeding may influence immunologic and metabolic function in a manner which will amplify responses to a subsequent inflammatory challenge.

Animals↗

PubMed2004

Loss of detoxification in inflammatory bowel disease: dysregulation of pregnane X receptor target genes.

BACKGROUND & AIMS: Phase 1, phase 2, and cellular efflux transporters are critical components in intestinal barrier function against xenobiotics and bacteria. We therefore performed global gene expression profiling in patients with ulcerative colitis (UC) and Crohn's disease as well as control specimens, with a special emphasis on genes involved in detoxification and epithelial membrane integrity. METHODS: Mucosal biopsy specimens from nonaffected regions of the colon and the terminal ileum were subjected to DNA microarray analysis and pathway-related data mining. Real-time reverse-transcription polymerase chain reaction was used for verification of selected regulated candidate genes in larger inflammatory bowel disease sample numbers and intestinal cell lines. RESULTS: Several dysregulated genes were identified in both disease groups and tissues. A set of genes coordinately down-regulated in the colon of patients with UC was composed of cellular detoxification and defense genes, which are target genes for the transcription factor pregnane X receptor (PXR). Messenger RNA expression of ABCB1 (MDR1) and PXR was significantly reduced in the colon of patients with UC but was unaffected in patients with Crohn's disease. In contrast to some of its target genes, the expression of PXR was not sensitive to tumor necrosis factor alpha stimulation of intestinal cell lines. CONCLUSIONS: A disease- and tissue-specific decrease in the expression of detoxification enzymes and ABC transporters was observed, which may be explained by a loss of PXR expression. Thus, dysregulation of xenobiotic metabolism and PXR activity in the gut is likely to contribute to the pathophysiology of UC.

ATP-Binding Cassette Transporters↗

PubMed1994

Bacterial translocation after burn injury: the contribution of ischemia and permeability changes.

Bacterial translocation (BT) has been shown to occur in stress and trauma. In this study, we examined the contribution of altered intestinal permeability (measured with 51Cr-EDTA) and intestinal blood flow (radioactive microspheres) to the loss of intestinal barrier function after burn injury. A 42.6 +/- 0.6% total body surface area scald burn was produced in Sprague-Dawley rats; sham burn animals served as controls. Rats (29 burn and 20 sham burn) were sacrificed 24 h postburn, and mesenteric nodes (MLN), cecum, spleen, and liver were cultured. The incidence of BT was significantly higher in burn compared to shams (MLN, 55 vs. 15%; spleen, 31 vs. 10%; liver, 31 vs. 10%; p < .05). Cecal concentration of Gram-negative bacteria were similar in all rats (5.2 +/- 0.2 x 10(8) colony forming units/g). 5 h postburn, intestinal blood flow decreased significantly in burn (1.60 +/- .20) compared to shams (2.49 +/- .24 ml/min/g, p = .01); at this time, plasma to luminal clearance of 51Cr-EDTA was greater in the burn (.146 +/- .033, N = 9) than in shams (.050 +/- .010 ml/min/100 g, N = 9, p = .001); 24 h postburn, there was no significant difference in intestinal blood flow in sham (2.86 +/- .46, N = 10) and burn rats (2.29 +/- .44 ml/min/g, N = 11); plasma to intestinal lumen clearance of 51Cr-EDTA was similar in sham (.054 +/- .010, N = 11) and burn rats (.051 +/- .006 ml/min/100 g, N = 12) 24 h postburn.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2000

Lisofylline ameliorates intestinal and hepatic injury induced by hemorrhage and resuscitation in rats.

OBJECTIVE: We sought to determine whether treatment with lisofylline (LSF) preserves intestinal barrier function in rats subjected to hemorrhagic shock and resuscitation (HS/R). SETTING: Research laboratory at a major university teaching hospital. DESIGN: Rats were bled to a mean arterial pressure of 30 mm Hg and maintained at that pressure for 90 mins. One group (n = 8) was treated with LSF (bolus doses of 15 mg/kg at 45 and 89 min plus infusion at 10 mg x kg(-1) x hr(-1)), whereas another group (n = 8) received only the lactated Ringer's solution (LRS) vehicle. At 90 mins, the animals were resuscitated with shed blood and LRS (55 mL x kg(-1) x hr(-1)). Intestinal mucosal permeability was determined by measuring the mucosal-to-serosal clearance of fluorescein isothiocyanate dextran (molecular weight = 4 kDa) into everted gut sacs. MEASUREMENTS AND MAIN RESULTS: Intestinal and hepatic blood flow (assessed by laser Doppler flowmetry) was greater in LSF-treated rats. Treatment with LSF ameliorated the development of histologic evidence of mucosal damage and hyperpermeability. Rats treated with LSF had lower plasma concentrations of the intracellular hepatic enzyme, aspartate aminotransferase. After 90 mins of resuscitation, concentrations of adenosine triphosphate in intestinal and hepatic tissue were greater in LSF-treated as compared with LRS-treated rats, but concentrations of the endogenous antioxidant, glutathione, in intestinal and hepatic tissue, although lower than in rats not subjected to HS/R, were similar in the two treatment groups. CONCLUSION: Treatment with LSF ameliorated HS/R-induced derangements in intestinal structure and function and hepatic injury, possibly by preserving microvascular perfusion and tissue adenosine triphosphate concentrations.

Animals↗

PubMed1998

IL-1beta and TNF-alpha, but not IFN-alpha, IFN-gamma, IL-6 or IL-8, are secretory mediators in human distal colon.

Inflammatory bowel disease (IBD) and HIV infection can cause diarrhoea which is accompanied by elevated cytokine levels. To elucidate a pathogenic role of cytokines, their effect on ion secretion was studied in human distal colon using the Ussing technique. Interluekin 1beta (IL-1beta) dose dependently increased short-circuit current (ISC). An ISC maximum of 2.5+/-0.3 micromol. h-1.cm-2 was reached at 20 ng/ml within 43+/-4 min. 22Na+ and 36Cl- fluxes were not altered and residual flux increased by 2.4+/-1.0 micromol.h-1.cm-2 indicating that the IL-1beta-induced ISC is based on electrogenic bicarbonate secretion. IL-1beta had no effect on HT-29/B6 epithlial monolayers suggesting that IL-1beta does not act directly on the epithelium. Furthermore, in human colon the effect was not attenuated by removal of the submucosa (total stripping) pointing to a mediation step via subepithlial cells in the lamina propria. While tetrodotoxin and the 5-lipoxygenase inhibitor ICI-230487 had no effect, indomethacin completely blocked IL-1beta action. Prostaglandin determination by RIA revealed an increased production of PGE2. At half maximum effective concentrations an additive action of tumour necrosis factor alpha (TNF-alpha) could be demonstrated on IL-1beta-induced secretion. Interferon alpha (IFN-alpha), IFN-gamma, IL-6, and IL-8 had no seretory effect in human distal colon. None of the investigated cytokines altered the intestinal barrier function. By their secretory effects IL-1beta and TNF-alpha, but not IFN-alpha, IFN-gamma, IL-6, and IL-8, may contribute to diarrhoea in IBD and AIDS.

Chlorides↗

PubMed1981

Passage of molecules through the wall of the gastrointestinal tract. Increased passive permeability in rat ileum after exposure to lysolecithin.

The interaction between lysolecithin and mucosal cells in the distal ileum has been studied. Using a rat experimental model, we determined the intestinal permeability to fluorescent dextran 3000 after exposure to different amounts of lysolecithin. At pH 7.3, lysolecithin, 10 mg/ml, significantly enhanced the transmural passage, and at pH 3.5, even 1 mg/ml markedly increased the permeability. However, when lysolecithin was incubated with homogenized mucosal cells, a rapid disappearance of the compound occurred; this was accompanied by formation of free fatty acids and minor formation of lecithin. It appears, therefore, that high concentrations of lysolecithin can impair the intestinal barrier function in the distal part of ileum but that the mucosal cells are well equipped with activities for the rapid removal of such high concentrations. This could be physiologically significant, since the mucosal cells could otherwise be faced with large amounts of lysolecithin that might facilitate the absorption of potentially antigenic and toxic compounds.

Animals↗

PubMed1999

Mechanisms and impact of enteric infections.

The increased recognition of both old and new enteric pathogens and their potential impact requires an improved understanding of pathogenesis and effective interventions. While the overwhelming mortality (> 3 million children per year) due to diarrheal diseases is well-recognized, the potential long-term impacts of enteric infections and early childhood diarrhea morbidity are just beginning to be appreciated. Furthermore, several enteric infections are now being recognized as causes of growth shortfalls with or without diarrhea; i.e., malnutrition may be one of the greatest yet of the "emerging infectious diseases." The increased appreciation of this extended impact calls for further quantification and improved understanding of the deranged physiology. In particular, persistent diarrheal illnesses exhibit common themes of blunted villi, disruption of intestinal barrier function and varying degrees of sub-mucosal inflammation for which lactulose/mannitol permeability and fecal lactoferrin provide respective quantification. Finally, such improved understanding will allow targeted interventions among those most vulnerable, which will enable further documentation of cost effectiveness and the potential for improved human development which is critical to reducing the widening disparity and population overgrowth which increasingly threaten our global security.

Animals↗