Gut Mucosal Barrier Dysfunction Research Articles

Partial fishmeal replacement by soybean meal induces fish growth retardation and gut inflammation via gut mucosal barrier dysfunction and dysbiosis in largemouth bass

The study aimed to investigate the effect of partial fishmeal replacement by soybean meal on fish growth, gut histology, oxidative stress, gut microbiota, and gene expression of inflammatory cytokines and tight junction proteins in largemouth bass (Micropterus salmoides). Four isonitrogenous and isolipidic diets were formulated: the FM diet contained 45 % fishmeal (FM diet) and did not contain soybean meal; diets SM25, SM50, and SM75 replaced 25 %, 50 %, and 75 % fishmeal protein in the FM group with soybean meal, respectively. Experimental fish (4.3 ± 0.1 g) were fed to apparent satiation for eight weeks. The results showed that replacing 25 % or more fishmeal decreased villus height, villus width, total superoxide dismutase (T-SOD) and catalase (CAT) activity levels, reduced glutathione contents, and Aurantimicrobium abundance; increased malonaldehyde contents and tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) expression; downregulated nuclear factor E2-related factor 2 (Nrf2), occludin, and zona occluding-1 (ZO-1), lysozyme (LYS) and hypoxia-inducible factor-1α (HIF-1α) expression, compared with FM (P < 0.05). Moreover, SBM50 and SBM75 decreased final body weight, weight gain rate, and specific growth rate, and increased the lamina propria width than FM (P < 0.05). Furthermore, SBM25 dramatically reduced Actinobacteriota, Enterococcus, Lactococcus, Leuconostoc, and Streptococcus abundance (P < 0.05). Compared to SM25, SM75 dramatically increased Brucella abundance (P < 0.05). Pearson correlation analysis indicated that tight junction proteins (ZO-1 and Occludin) and gut microbiota (Aurantimicrobium and Brucella) have a significant association with gut inflammation and fish growth (P < 0.05). These results showed that gut dysbiosis and intestinal mucosal barrier dysfunction are major contributors to the soybean meal-induced growth retardation and gut inflammation in fish.

Establishing the cut-offs of leaky gut syndrome diagnostic: where are we now?

Abstract Gastrointestinal mucosa forms a surface that interacts with many external factors. Beside the digestion and absorption of nutrients, it also acts as a barrier to allergens, pathogens, and toxins. Leaky gut syndrome is defined as a gut mucosal barrier dysfunction, which results in abnormally increased intestinal permeability. Research shows that leaky gut syndrome (LGS) has a pathogenetic relationship with a series of gastrointestinal and extra-intestinal disorders. This review discusses the current understanding of intestinal barrier composition and pathological contribution of LGS to various diseases. The major aim of this paper is to review different methods for diagnostics and evaluation of intestinal wall permeability, identifying their priorities and disadvantages.

Alterations of the Predominant Fecal Microbiota and Disruption of the Gut Mucosal Barrier in Patients with Early-Stage Colorectal Cancer.

Growing evidence indicated that the gut microbiota was the intrinsic and essential component of the cancer microenvironment, which played vital roles in the development and progression of colorectal cancer (CRC). In our present study, we investigated the alterations of fecal abundant microbiota with real-time quantitative PCR and the changes of indicators of gut mucosal barrier from 53 early-stage CRC patients and 45 matched healthy controls. We found that the traditional beneficial bacteria such as Lactobacillus and Bifidobacterium decreased significantly and the carcinogenic bacteria such as Enterobacteriaceae and Fusobacterium nucleatum were significantly increased in CRC patients. We also found gut mucosal barrier dysfunction in CRC patients with increased levels of endotoxin (LPS), D-lactate, and diamine oxidase (DAO). With Pearson's correlation analysis, D-lactate, LPS, and DAO were correlated negatively with Lactobacillus and Bifidobacterium and positively with Enterobacteriaceae and F. nucleatum. Our present study found dysbiosis of the fecal microbiota and dysfunction of the gut mucosal barrier in patients with early-stage CRC, which implicated that fecal abundant bacteria and gut mucosal barrier indicators could be used as targets to monitor the development and progression of CRC in a noninvasive and dynamic manner.

Plasmadiafiltration ameliorating gut mucosal barrier dysfunction and improving survival in porcine sepsis models.

BackgroundThe object of this study is to explore whether the plasmadiafiltration (PDF) is more effective in improving the intestinal mucosal barrier function by removing more key large molecular inflammatory mediators and then prolonging the survival time.MethodsTotally, 24 porcine sepsis models induced by cecal ligation and puncture (CLP) operation were randomly divided into three groups: PDF group, high-volume hemofiltration (HVHF) group, and control group, and received 8 h treatment, respectively. The expression of ZO-1 and occludin in intestinal mucosal epithelial cells were detected by immunohistochemistry, and apoptotic protein caspase-3-positive lymphocytes were signed in mesenteric lymph nodes by TUNEL staining. The hemodynamic parameters were measured by invasive cavity detection. The tumor necrosis factor alpha (TNFα) and high-mobility group protein 1 (HMGB1) were tested by ELISA method. And then, the survival curves with all-cause death were compared with three groups.ResultsPDF led to a superior reversal of sepsis-related hemodynamic impairment and serum biochemistry abnormalities and resulted in longer survival time compared with HVHF and control (p < 0.01). Definitive protection from excessive TNF-α and HMGB1 response were only achieved by PDF. A more regular distribution pattern of ZO-1 and occludin along the epithelium was found in PDF animals (p < 0.01). The presence of apoptotic lymphocytes was significantly reduced in the PDF animals (p < 0.01).ConclusionsPDF can effectively eliminate more pivotal inflammatory mediators of TNFα and HMGB1 and reduce the inflammation damage of the intestinal mucosal barrier and apoptosis of lymphocyte then improve the circulation function and prolong the survival time.

Gut Mucosal Barrier Dysfunction, Microbial Dysbiosis, and Their Role in HIV-1 Disease Progression.

Distinct pathological events occur within the gastrointestinal (GI) tract of Asian macaques with progressive simian immunodeficiency virus (SIV) infection and humans with human immunodeficiency virus type 1 (HIV-1) infection that are critical in shaping disease course. These events include depletion and functional alteration of GI-resident CD4(+) T cells, loss of antigen-presenting cells, loss of innate lymphocytes, and possible alterations to the composition of the gut microbiota. These contribute to structural damage to the GI tract and systemic translocation of GI tract microbial products. These translocated microbial products directly stimulate the immune system, and there is now overwhelming evidence that this drives chronic immune activation in HIV-1 and SIV infection. While combined antiretroviral therapy (cART) in HIV-1-infected subjects generally allows for immune reconstitution in peripheral blood, reconstitution of the GI tract occurs at a much slower pace, and both immunological and structural abnormalities persist in the GI tract. Importantly, studies of large cohorts of individuals have linked suboptimal GI reconstitution to residual inflammation and heightened morbidities in HIV-1-infected cART recipients. As a result, current era treatments aimed at augmenting restoration of the GI tract hold promise in returning cART recipients to full health.

Formula milk alters microbial diversity in porcine colon and impacts immune response

Formula feeding in infants is associated with increased risk of upper respiratory tract infections, allergies and gut dysfunction possibly by compromising gut immune system. We hypothesized that formula feeding alters the host microbiome, resulting in morphology changes and modulation of large intestine immune response. This hypothesis was tested in piglets fed formula diet from postnatal day (PND) 2 to PND 21(n=12, either sex, age‐matched) and compared to sow fed control group (n=12) by measuring the distal colon microbiome, cytokine mRNA and histomorphometry of proximal (PC) and distal colon (DC) on day 21. Microbial richness and diversity was measured via 16sRNA amplicon sequencing using V4 variable primers. Data analyses were carried out by using QIIME 1.9.1. Principal component analyses (PCoA) indicated clear separation of the formula fed group from the control sow group. Formula feeding showed significantly more microbial diversity (Bonferroni corrected, p=0.01) in comparison to the sow fed group. The order of microbial abundance was Bacteroidietes&gt;Firmicutes&gt; Proteobacteria&gt;Verrucomicrobiae at phylum level in both formula and sow‐fed groups. Formula feeding showed 2‐ to 8‐fold abundance of Bacteroidaceae, Porphyromondadaceae, Rokenellaceae, Odoribacteraceae within Bacteroides phylum at family level in comparison to sow group. However, in the sow fed group 5‐fold higher Paraprevotellaceae was observed (FDR corrected, p&lt;0.01). In Firmicutes only Streptococcus spp was 5‐fold higher in formula fed piglets (FDR corrected, p&lt;0.05). Furthermore, 11‐fold higher Gammaproteobacteria and 20 folder higher Verrucomicrabae was observed in formula fed pigelts (FDR corrected, p&lt;0.01) in comparison to sow‐fed, indicating that formula‐fed piglets show more microbial diversity than sow fed piglets in distal colon. Cytokine analyses showed 1.5‐ to 2.0‐fold increases (p&lt;0.05) in gene expression of BMP4 (gut mucosal barrier dysfunction), CCL21 (critical for dendric cell migration), CCL25 (helps in gut‐specific migration of leukocytes), CSF3 (granulocyte development), VEGF‐A (growth factor), and 1.5‐ to 4‐fold (p&lt;0.05) decreases in CXCL‐11 (Th1‐associated chemokines), IL‐27 (B and T lymphocytes regulation) in PC and DC in formula group, suggesting the participation of specific cytokines in alteration of mucosal barrier and activation of gut‐associated immune response. No significant changes were found in length and perimeter of the large intestine; however, a significant increase in crypt density (p&lt;0.05) was noticed in PC of formula‐fed group, suggesting alterations in colon morphology. In summary, formula diet‐driven microbiome changes accompanied alterations in colon crypt density and cytokine response. Studies are being carried out to determine if the formula diet impacts on mucosa membrane are a consequence of microbial interactions with the developing gut‐associated lymphoid tissue.Support or Funding InformationUSDA‐ARS Project 6026‐51000‐010‐05S.

Relationship between gut mucosal barrier dysfunction and immune response in patients with early severe acute pancreatitis

Objective To explore the relationship between gut mucosal barrier dysfunction and immune response in patients with early severe acute pancreatitis (SAP).Method 46 patients with early SAP were enrolled into this study from January 2010 to December 2012.Results The levels of endotoxin,the lactulose/mannitol (L/M) ratio,the D (-)-lactate concentration,and the proportion of HLA-DR-positive monocytes all decreased from a high level,while the frequency of Tregs increased during the first 14 days.The Th1/Th2 ratio decreased,with a decreased Th1 and an increased Th2 profile in the first week,but it subsequently increased,with an increased Th1 profile.Conclusions The data from this study showed that immunosuppression and immune imbalance happened in patients with early SAP,and showed a positive relationship with gut mucosal barrier dysfunction in patients with early SAP.Thus,early protection of the function of intestinal mucosal barrier is important in the treatment of SAP. Key words: Severe acute pancreas ; Gut mucosal barrier; Immune response

Probiotic pretreatment improves survival and prevents gut mucosal barrier dysfunction in sepsis

The gut is the largest immune organ and plays a central role in the promotion of systemic inflammatory responses [1]. Perturbations of intestinal epithelial homeostasis during sepsis include increased proinflammatory cytokine production, increased intestinal permeability and apoptosis [2-6]. Healthy gut is essential to promote host health and prevent organ dysfunction in sepsis. Probiotics seem to keep gut homeostasis through different pathways, such as the modulation of microbial activity, energy regulation, anti-inflammatory cytokine production, gene expression and cell differentiation [7]. Probiotics have been shown an effective treatment in various clinical conditions, although the potential benefits of probiotic treatment in sepsis remain largely undefined. The aim of the present study was to investigate the effect of probiotic treatment on gut dysfunction and inflammatory signaling in septic rats.

Immunosuppression and the infection caused by gut mucosal barrier dysfunction in patients with early severe acute pancreatitis

Few data are available on the relationship between immune response and the infection caused by gut mucosal barrier dysfunction in patients with severe acute pancreatitis (SAP). The aim of this study was to investigate the immune response to gut mucosal barrier dysfunction in patients with early SAP. The results showed that the levels of endotoxin, the lactulose/mannitol (L/M) ratio, the D(-)-lactate concentration, the proportion of HLA-DR-positive monocytes, and the expression levels of TNF-α, IL-6 and IL-10 all decreased from a high level while the frequency of Tregs increased during the first 14 days. The Th1/Th2 ratio was decreased, with a decreased Th1 and an increased Th2 profile, in the beginning, but it was subsequently increased, with an increased Th1 profile. The data from this study showed that immunosuppression, the shift of the Th1/Th2 balance toward a Th2 response, increased Tregs, and related inflammatory cytokines are involved in the complex process of inflammation and infection caused by gut mucosal barrier dysfunction in patients with early SAP.

Protective Effects of Free Radical Scavenger Edaravone Against Xanthine Oxidase–Mediated Permeability Increases in Human Intestinal Epithelial Cell Monolayer

The barrier function of the intestinal mucosa can be disturbed under a variety of pathologic insults. Reactive oxygen species play an important role in intestinal mucosal injury. This in vitro study examines the hypothesis that a free radical scavenger, edaravone (ED), ameliorates gut epithelial permeability increase caused by xanthine oxidase (XO)-mediated oxidative stress in a cell monolayer model. Human intestinal epithelial (HIE) cells were grown as monolayer in bicameral chambers. Twenty milliunits per milliliter of XO+0.25 mM of xanthine (XO+X group) or saline (control) were administered into the basal chambers. Another set of chambers was treated with XO+X and 0.6 mg/ml of ED (XO+X+ED group). The permeability was assessed by quantifying the transepithelial passage of fluorescence in isothiocyanate-labeled dextran. In another series of experiments, Escherichia coli C-25 was also applied in an apical chamber to evaluate the bacterial translocation through the monolayer. The concentration of the fluorescence in isothiocyanate-labeled dextran in the basal chamber of the control group was significantly higher than the control (705 +/- 50.2 vs 155 +/- 45.4 mg/dl, P < .01). Treatment with ED prevented this permeability increase induced by the oxidative stress (P < .01). The incidence of bacterial translocation through the HIE monolayer in XO+X group was also higher than that of the control group (75 vs 13%, P < .05). Increased HIE cell monolayer permeability mediated by xanthine and XO was significantly attenuated with ED. This synthesized radical scavenger may have potential clinical applications against gut mucosal barrier dysfunction.

Modulation of the Maturing Gut Barrier and Microbiota: A Novel Target in Allergic Disease

The underlying denominators and treatment targets in atopic disease may be outlined as aberrant barrier functions of the skin epithelium and gut mucosa, and dysregulation of the immune response to ubiquitous environmental antigens. The route of sensitization varies with age, dietary antigens predominating in infancy. The immaturity of the immune system and the gastrointestinal barrier may explain the peak prevalence of food allergies at an early age. Dietary methods to control symptoms and reduce the risk of allergic disease have hitherto focused on elimination diets, alone or in combination with other environmental measures. The results have not been satisfactory regarding long-term prevention, primary or secondary. In view of the increasing burden of the abnormalities, new approaches are urgently needed for the management of allergic diseases and their prevention in at-risk infants. Novel methods here may include probiotics to counteract the immunological and gut mucosal barrier dysfunction associated with allergic disease, and thereby to strengthen endogenous defence mechanisms. Notwithstanding the demonstrations of important immunoregulatory potential of the well-balanced gut microbiota, the major objective health benefits of specific strains in allergic infants have only recently been clinically proven. Advances here have prompted enthusiasm in the scientific community and food industry and have fuelled research activities currently focusing firstly on identification of specific strains with anti-allergenic potential, and secondly on the question how food matrix and dietary content interact with the most efficacious probiotic strains.

Intestinal alkaline phosphatase is a gut mucosal defense factor maintained by enteral nutrition

Under conditions of starvation and disease, the gut barrier becomes impaired, and trophic feeding to prevent gut mucosal atrophy has become a standard treatment of critically ill patients. However, the mechanisms responsible for the beneficial effects of enteral nutrition have remained a mystery. Using in vitro and in vivo models, we demonstrate that the brush-border enzyme, intestinal alkaline phosphatase (IAP), has the ability to detoxify lipopolysaccharide and prevent bacterial invasion across the gut mucosal barrier. IAP expression and function are lost with starvation and maintained by enteral feeding. It is likely that the IAP silencing that occurs during starvation is a key component of the gut mucosal barrier dysfunction seen in critically ill patients.

Pathways involved in gut mucosal barrier dysfunction induced in adult rats by maternal deprivation: corticotrophin‐releasing factor and nerve growth factor interplay

Neonatal maternal deprivation (NMD) increases gut paracellular permeability (GPP) through mast cells and nerve growth factor (NGF), and modifies corticotrophin-releasing factor (CRF) and corticosterone levels. CRF, corticosterone and mast cells are involved in stress-induced mucosal barrier impairment. Consequently, this study aimed to specify whether corticosteronaemia and colonic expression of both preproCRF and CRF are modified by NMD, and to determine if altered expression may participate in the elevated GPP in connection with NGF and mast cells. Male Wistar rat pups were either separated from postnatal days 2-14, or left undisturbed with their dam. At 12 weeks of age, adult rats were treated with mifepristone (an antagonist of corticoid receptors), alpha-helical CRF((9-41)) (a non-specific CRF receptor antagonist), or SSR-125543 (CRF-R(1) receptor antagonist). We also determined corticosteronaemia and both colonic preproCRF and CRF expression. Then, control rats were treated by CRF, doxantrazole (mast cell stabilizer), BRX-537A (a mast cell activator) and anti-NGF antibody. NMD did not modify colonic CRF level but increased colonic preproCRF expression and corticosteronaemia. Peripheral CRF, via CRF-R(1) receptor, but not corticosterone, was involved in the elevated GPP observed in these rats, through a mast-cell-mediated mechanism, since the increase of GPP induced by exogenous CRF was abolished by doxantrazole. Anti-NGF antibody treatment also reduced the elevated GPP induced by CRF or BRX-537A. CRF acts through CRF-R(1) receptors to stimulate NGF release from mast cells, which participates in the elevated GPP observed in NMD adult rats. This suggests that early traumatic experience induced neuro-endocrine dysfunction, involved in alterations of gut mucosal barrier.

The role of RAGE in the pathogenesis of intestinal barrier dysfunction after hemorrhagic shock

The receptor for advanced glycation end products (RAGE) has been implicated in the pathogenesis of numerous conditions associated with excessive inflammation. To determine whether RAGE-dependent signaling is important in the development of intestinal barrier dysfunction after hemorrhagic shock and resuscitation (HS/R), C57Bl/6, rage(-/-), or congenic rage(+/+) mice were subjected to HS/R (mean arterial pressure of 25 mmHg for 3 h) or a sham procedure. Twenty-four hours later, bacterial translocation to mesenteric lymph nodes and ileal mucosal permeability to FITC-labeled dextran were assessed. Additionally, samples of ileum were obtained for immunofluorescence microscopy, and plasma was collected for measuring IL-6 and IL-10 levels. HS/R in C57Bl/6 mice was associated with increased bacterial translocation, ileal mucosal hyperpermeability, and high circulating levels of IL-6. All of these effects were prevented when C57Bl/6 mice were treated with recombinant human soluble RAGE (sRAGE; the extracellular ligand-binding domain of RAGE). HS/R induced bacterial translocation, ileal mucosal hyperpermeability, and high plasma IL-6 levels in rage(+/+) but not rage(-/-) mice. Circulating IL-10 levels were higher in rage(-/-) compared with rage(+/+) mice. These results suggest that activation of RAGE-dependent signaling is a key factor leading to gut mucosal barrier dysfunction after HS/R.

Intestinal epithelial hyperpermeability: update on the pathogenesis of gut mucosal barrier dysfunction in critical illness.

Tight junctions between adjacent epithelial cells are essential for the maintenance of compositionally distinct fluid compartments in various organs, such as the liver, lungs, kidneys, and intestine. These epithelial organs are commonly affected in the condition known as multiple organ dysfunction syndrome, which can complicate the clinical course of patients with sepsis or other conditions associated with poorly controlled systemic inflammation. The gut serves as a useful model for this problem, and studies using reductionist in vitro models and experiments carried out using laboratory animals are starting to clarify the cellular and biochemical mechanisms that are responsible for intestinal epithelial hyperpermeability secondary to critical illness. One key factor that has been identified is excessive production of nitric oxide and related species, although other factors, such as increased expression of the cytokine interleukin 6, appear to be important as well. A newly described, cytokine-like molecule, high-mobility group B1, increases permeability of cultured epithelial monolayers in vitro and murine ileal mucosa in vivo. Epithelial dysfunction may be a common final pathway contributing to organ dysfunction in sepsis and other forms of critical illness.

Increased gut permeability and bacterial translocation in Pseudomonas pneumonia-induced sepsis.

Gut injury and barrier dysfunction may contribute to the pathogenesis of sepsis and multiple organ dysfunction syndrome. The objective of this study was to determine whether gut injury could be demonstrated in hyperdynamic, normotensive sepsis induced by Pseudomonas pneumonia. Randomized animal study. University laboratory. Adult male Sprague-Dawley rats. Sepsis was induced by intratracheal instillation of Pseudomonas aeruginosa. We measured gut mucosal and microvascular injury. In the first experiment, gut mucosal permeability was measured by 51Cr-EDTA uptake in control (n = 6), pneumonia 20-hr (n = 4), and pneumonia 40-hr (n = 4) groups. In the second experiment, microvascular permeability was measured by albumin extravasation, and morphologic abnormalities were scored in control (n = 6), pneumonia 20-hr (n = 9), and pneumonia 40-hr (n = 11) groups. Bacterial translocation to mesenteric lymph nodes was determined in both experiments. Cardiac index increased significantly in the pneumonia compared with control rats (64+/-2.1, 68+/-1.3, vs. 46+/-2 mL/min/100 g, p < .05; all results are listed in the order of pneumonia 20-hr, pneumonia 40-hr, and control groups as mean +/- SEM). Mean blood pressure was normal and was not different between groups (112+/-3, 111+/-2, vs. 118+/-2 mm Hg). 51Cr-EDTA recovery in urine 6 hrs after gavage increased significantly in both pneumonia groups vs. controls (17.5+/-2.2%, 17.9+/-7%, vs. 4+/-0.7%; p < .05). Albumin leak (tissue/plasma ratio) increased significantly in the middle and distal small intestine in the pneumonia 40-hr group vs. controls (0.68+/-0.05, 0.76+/-0.07, vs. 0.45+/-0.04, p < .05 in the middle small gut; 0.75+/-0.09, 0.85+/-0.07, vs. 0.51+/-0.05, p < .05 in the distal small gut). Bacterial translocation to mesenteric lymph nodes increased significantly in pneumonia 40-hr rats vs. controls (positive culture 67% vs. 8%; p < .05). This study demonstrates gut mucosal and microvascular injury and gut barrier dysfunction in normotensive sepsis secondary to bacterial pneumonia. The mechanism and significance of the injury need to be determined.

Inhibition of inducible nitric oxide synthase ameliorates endotoxin- induced gut mucosal barrier dysfunction in rats

BACKGROUND & AIMS: The permeability of intestinal epithelial monolayers increases after exposure to nitric oxide. The aim of this study was to investigate the role of excessive NO production on intestinal barrier function in rats injected with lipopolysaccharide (LPS).METHODS: Rats were injected with saline or LPS (5 mg/ kg). Bacterial translocation to mesenteric lymph nodes, liver, and spleen was assessed 24 hours after LPS injection. Mucosal permeability was determined by loading fluorescein-labeled dextran (mol wt, 4000 daltons) into an intestinal segment and measuring its appearance in plasma. Intestinal mucosal mitochondrial respiration was assessed using 3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyltetrazolium bromide.RESULTS: Intestinal tissue from LPS-challenged rats showed upregulation of inducible NO synthase (iNOS) messenger RNA expression and subsequent up-regulation of iNOS enzymatic activity. Plasma concentrations of nitrite plus nitrate (NO2-/NO3-) were increased for at least 24 hours after injection of LPS. Treatment with the selective iNOS inhibitor, aminoguanidine, inhibited iNOS enzymatic activity and overproduction of NO2-/NO3-. LPS-induced bacterial translocation was reduced by aminoguanidine. LPS-induced intestinal hyperpermeability was ameliorated by both aminoguanidine and another selective iNOS inhibitor, S-methylisothiourea. LPS depressed intestinal mucosal mitochondrial function, and this effect was ameliorated by aminoguanidine.CONCLUSIONS: Overproduction of NO may contribute to intestinal barrier dysfunction in LPS challenged rats, possibly by interfering with mitochondrial oxidative metabolism.(Gastroenterology 1997 Oct;113(4):1246-57)

Increased Gut Permeability to Fluorescein Isothiocyanate-Dextran after Total Parenteral Nutrition in the Rat

Sepsis with subsequent multiple organ failure is the commonest complication seen in the surgical intensive care unit today. A gut mucosal barrier dysfunction is assuming an increasingly important role as one possible explanation for the initiation of the septic process. It is known that the gut bacteria and endotoxins can, in the presence of a seemingly intact epithelium, translocate to extraintestinal sites, but the exact mechanism behind this process is not understood. In the present study we have approached this problem by testing the gut permeability to two macromolecules, bovine serum albumin (BSA) and fluorescein isothiocyanate (FITC)-dextran, after 7 days of enteral or parenteral nutrition in the rat. The plasma values of FITC-dextran after 4 h of marker feeding showed a significant increase in gut permeability after parenteral but not after enteral nutrition as compared with the controls. The plasma values of BSA, however, did not show any significant change in any of the groups. Thus, parenteral nutrition, with the changes occurring in the gut mucosa, may be one of the etiologic co-factors behind a gut mucosal barrier dysfunction, eventually leading to absorption of noxious agents into the systemic circulation with subsequent multiple organ failure.