Changes In Intestinal Permeability Research Articles

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.

Effect of glutamine on the intestinal permeability changes induced by indomethacin in humans.

Long-term non-steroidal anti-inflammatory drug (NSAID) intake may induce increased intestinal permeability, eventually resulting in enteropathy. Because increased permeability might be related to cell damage resulting from energy depletion, it was hypothesized that glutamine--the major energy source of the intestinal mucosal cell--might prevent permeability changes. The 6-h urinary excretion of 51Cr-EDTA after an oral load of 51Cr-EDTA was used in this study as a measure for intestinal permeability. Healthy volunteers underwent a series of permeability tests: (i) basal test; (ii) test following NSAID (indomethacin); (iii) test following NSAID in combination with glutamine and/or misoprostol. The NSAID induced increased permeability in all volunteers. Pre-treatment with glutamine (3x7 g daily, 1 week before NSAID-dosing) did not prevent the NSAID-induced increase in permeability. Multiple doses of glutamine close in time to NSAID-dosing resulted in significantly lower permeability compared to the NSAID without glutamine. Co-administration of misoprostol with the multiple-dose scheme of glutamine resulted in a further reduction in the NSAID-induced increase in permeability. Glutamine decreases the permeability changes caused by NSAID-dosing when it is administered close in time, and misoprostol has a synergistic effect.

Intestinal permeability in liver cirrhosis.

To determine the changes in intestinal permeability in liver cirrhosis and to investigate whether intestinal permeability relates to the stage and aetiology of cirrhosis or existence of spontaneous bacterial peritonitis (SBP). A prospective study of intestinal permeability in patients with cirrhosis. Gastroenterology and Nuclear Medicine Departments of Ege University Hospital. Intestinal permeability was assessed in 44 consecutive patients with cirrhosis and 10 healthy volunteers by measuring 24 h urine excretion of (99m)technetium diethyl triamine penta-acetic acid (99mTc DTPA). Cases with an associated disease, impaired renal function, continuing alcohol consumption and drug intake which is known to have an effect on intestinal permeability were excluded. Comparisons of 24 h urine excretion of 99mTc DTPA were made between the groups of cirrhotics and controls, different grades of cirrhosis (according to Child-Pugh criteria), alcoholic and non-alcoholic cirrhotics and cirrhotic patients with and without SBP. Patients with cirrhosis excreted 99mTc DTPA significantly more than controls (11.56 +/- 8.96% in cirrhotics and 4.30 +/- 1.49% in controls, P < 0.0001). There was no relationship of 24 h urine excretion of the tracer with the grade and aetiology of cirrhosis (12.20 +/- 9.47%, 11.41 +/- 9.84%, and 11.09 +/- 8.42%, in Child A, B, and C groups and 8.45 +/- 6.57% and 12.05 +/- 9.25% in alcoholic and non-alcoholic cirrhotics, respectively). No significant difference was found between cirrhotic patients with and without SBP in terms of excretion of the administered dose of 99mTc DTPA (9.98 +/- 9.47% and 12.20 +/- 8.82%, respectively). This study shows that intestinal permeability increased in cirrhotic patients regardless of the grade and aetiology of disease. The presence of SBP does not seem to be due to increased intestinal permeability.

Intestinal microcirculation and gut permeability in acute pancreatitis: early changes and therapeutic implications

Translocation of bacteria from the intestine causes local and systemic infection in severe acute pancreatitis. Increased intestinal permeability is considered a promoter of bacterial translocation. The mechanism leading to increased gut permeability may involve impaired intestinal capillary blood flow. The aim of this study was to evaluate and correlate early changes in capillary blood flow and permeability of the colon in acute rodent pancreatitis of graded severity. Edematous pancreatitis was induced by intravenous cerulein; necrotizing pancreatitis by intravenous cerulein and intraductal glycodeoxycholic acid. Six hours after induction of pancreatitis, the permeability of the ascending colon was assessed by the Ussing chamber technique; capillary perfusion of the pancreas and colon (mucosal and subserosal) was determined by intravital microscopy. In mild pancreatitis, pancreatic capillary perfusion remained unchanged (2.13 ± 0.06 vs. 1.98 ± 0.04 nl·min −1·cap −1 [control]; P = NS), whereas mucosal (1.59 ± 0.03 vs. 2.28 ± 0.03 nl·min −1·cap −1 [control]; P <0.01) and subserosal (2.47 ± 0.04 vs. 3.74 ± 0.05 nl·min −1·cap −1 [control]; P <0.01) colonic capillary blood flow was significantly reduced. Severe pancreatitis was associated with a marked reduction in both pancreatic (1.06 ± 0.03 vs. 1.98 ± 0.04 nl·min −1·cap −1 [control]; P <0.01) and colonic (mucosal: 0.59 ± 0.01 vs. 2.28 ± 0.03 nl·min −1·cap −1 [control], P <0.01; subserosal: 1.96 ± 0.05 vs. 3.74 ± 0.05 nl·min −1·cap −1 [control], P <0.01) capillary perfusion. Colon permeability tended to increase with the severity of the disease (control: 147 ± 19 nmol·hr −1·cm −2; mild pancreatitis: 158 ± 23 nmol·hr −1·cm −2; severe pancreatitis: 181 ± 33 nmol·hr −1·cm −2; P = NS). Impairment of colonic capillary perfusion correlates with the severity of pancreatitis. A decrease in capillary blood flow in the colon, even in mild pancreatitis not associated with significant protease activation and acinar cell necrosis or impairment of pancreatic capillary perfusion, suggests that colonic microcirculation is especially susceptible to inflammatory injury. There was no significant change in intestinal permeability in the early stage of pancreatitis, suggesting a window of opportunity for therapeutic interventions to prevent the later-observed increase in gut permeability, which could result in improved intestinal microcirculation.

Intestinal permeability and inflammation in patients on NSAIDs

Background—The frequency with which non-steroidal anti-inflammatory drugs (NSAIDs) increase small intestinal permeability and cause inflammation is uncertain.Aims—To examine small intestinal permeability and inflammation in a large number of patients on...

Introduction of enteral feeding in neonates on extracorporeal membrane oxygenation after evaluation of intestinal permeability changes

Background/Purpose : Neonates meeting criteria for extracorporeal membrane oxygenation (ECMO) often suffer from variable periods of hypoxia. During ECMO, starvation of the gut is common practice in many centres as splanchnic ischemia results in loss of intestinal integrity, which in turn predisposes for bacterial translocation and sepsis and eventually necrotizing enterocolitis (NEC) and multiorgan failure. However, minimal enteral feeding is thought to be of benefit in the critically ill. Data on intestinal integrity in newborns on ECMO and the effects of enteral nutrition are not available. This study prospectively evaluates the changes in small intestinal integrity in 16 neonatal ECMO patients. Methods : With 2-day intervals, excretion percentages of lactulose/ l-rhamnose (nonmediated diffusion), d-xylose (passive), and 3-O-methyl- d-glucose (active carrier-mediated transport) were measured by gas-liquid chromatography in a 4-hour urine sample. After obtaining baseline data in nine patients, enteral feeding was started in the next seven patients between the third and the ninth day of ECMO. Results : Thirteen patients had increased lactulose/ l-rhamnose ratios (>0.05) consistent with increased intestinal permeability. In three patients the lactulose/ l-rhamnose ratios were within the normal range. D-xylose excretion percentages were normal (or slightly increased) in 11 patients consistent with normal (or increased) passive carrier-mediated transport. 3-O-methyl- d-glucose excretion percentages were decreased (<10%) in all but one patient, consistent with decreased active carrier-mediated transport. After introduction of enteral nutrition no significant changes of these parameters were seen. Conclusions : The authors conclude that intestinal integrity is compromised in neonates on ECMO and that introduction of enteral nutrition does not result in further deterioration. This conclusion does not support the practice of withholding enteral nutrition in critically ill newborns supported by ECMO.

TOXICOKINETICS OF INDOMETHACIN-INDUCED INTESTINAL PERMEABILITY IN THE RAT

Numerous studies in humans have demonstrated increases in intestinal permeability resulting from the administration of non-steroidal anti-inflammatory drugs (NSAIDs). The increased permeability correlates well with ulceration. The time course of the changes in intestinal permeability, however, has not been studied, which makes comparative studies between different NSAIDs or different formulations of the same drug difficult. In the present study we have administered single doses of indomethacin to examine both the time course and pharmacokinetic/pharmacodynamic relationships of intestinal permeability in rats estimated by following the urinary excretion of [ 51Cr]-EDTA. The change in intestinal permeability was both time- and dose-dependent. Following both 10 mg kg −1and 20 mg kg −1oral doses of indomethacin, there was a rapid rise in intestinal permeability to a maximum level, after at least 12 h post-dose, which is longer than those previously observed for ibuprofen, ketoprofen, flurbiprofen and naproxen. The maximal effect lasted 12 and 36 h following 10 and 20 mg kg −1doses, respectively. The side-effect–plasma concentration relationship demonstrated a counter-clockwise hysteresis. The relationship between the observed side-effect and the estimated deep effect compartment concentration was, on the other hand, linear. In comparative permeability studies of NSAIDs the time of administration, concentration and drug dependencies should be considered.

Nonsteroidal anti-inflammatory drug enteropathy in rats: Role of permeability, bacteria, and enterohepatic circulation

BACKGROUND & AIMS: The pathogenesis of nonsteroidal anti-inflammatory drug (NSAID)-induced small intestinal damage remains poorly understood. The aim of this study was to examine the relative importance of the three suggested components of the pathogenesis of NSAID enteropathy, namely, epithelial permeability, enteric bacterial numbers, and enterohepatic recirculation, using an NSAID derivative (nitrofenac) that does not cause small intestinal damage. METHODS: Rats were given diclofenac or nitrofenac at 12-hour intervals. Epithelial permeability to [51Cr]-ethylenediaminetetraacetic acid and enteric bacterial numbers were determined after 1-4 doses of the drugs. Serum levels and biliary excretion of the two drugs were determined by high-performance liquid chromatography. RESULTS: Diclofenac caused a progressive increase in epithelial permeability, marked increases in enteric gram-negative bacterial numbers, and frank intestinal ulceration. Nitrofenac caused similar changes in intestinal permeability after a single dose but no further increase with repeated administration. Moreover, nitrofenac had no effect on enteric bacterial numbers and did not cause frank ulceration. Unlike diclofenac, nitrofenac did not undergo extensive enterohepatic recirculation. Two other NSAIDs that do not undergo enterohepatic recirculation (nabumetone and aspirin) also did not modify enteric bacterial numbers or cause intestinal ulceration. CONCLUSIONS: Enterohepatic recirculation of NSAIDs is of paramount importance in the pathogenesis of enteropathy caused by these drugs, whereas suppression of prostaglandin synthesis is relatively unimportant. (Gastroenterology 1997 Jan;112(1):109-17)

Intestinal permeability and function in dogs with small intestinal bacterial overgrowth

Small intestinal bacterial overgrowth (SIBO) has been reported to occur commonly in dogs with signs of chronic intestinal disease. There are usually few intestinal histological changes, and it is uncertain to what extent bacteria cause mucosal damage. The aim of this study was to apply a differential sugar absorption test for intestinal permeability and function to the objective assessment of intestinal damage in dogs with SIBO. Studies were performed on 63 dogs with signs of chronic small and, or, large bowel disease, in which SIBO (greater than 10(5) total or greater than 10(4) anaerobic colony forming units/ml) was diagnosed by quantitative culture of duodenal juice obtained endoscopically. None of the dogs had evidence of intestinal pathogens, parasites, systemic disease or pancreatic insufficiency. differential sugar absorption was performed by determining the ratios of urinary recoveries of lactulose/rhamnose (L/R ratio, which reflects permeability) and D-xylose/3-O-methylglucose (X/G ratio, which reflects intestinal absorptive function) following oral administration. Dogs with SIBO comprised 28 different breeds, including 13 German shepherd dogs. SIBO was aerobic in 18/63 dogs (29 per cent), and anaerobic in 45/63 (71 per cent). Histological examination of duodenal biopsies showed no abnormalities in 75 per cent, and mild to moderate lymphocytic infiltrates in 25 per cent of the dogs. The L/R ratio was increased (greater than 0.12) in 52 per cent, and the X/G ratio reduced (less than 0.60) in 33 per cent of the dogs. Differential sugar absorption was repeated in 11 dogs after their four weeks of oral antibiotic therapy. The L/R ratio declined in all 11 dogs (mean +/- SD pre: 0.24 +/- 0.14; post: 0.16 +/- 0.11; P < 0.05), but changes in the X/G ratio were more variable. These findings show that SIBO is commonly associated with mucosal damage not detected on histological examination of intestinal biopsies, and that changes in intestinal permeability following oral antibiotics may be used to monitor response to treatment.

Assessing the site of increased intestinal permeability in coeliac and inflammatory bowel disease.

The precise site of intestinal permeability changes in patients with coeliac and inflammatory bowel disease is unknown. To design a non-invasive technique for the localisation of altered gastrointestinal permeability to 51chromium labelled EDTA (51CrEDTA). The method depends on comparing and defining concentration/time profiles in serum of a series of simultaneously ingested indicators with a well defined absorption site (3-0-methyl-D-glucose (jejunal indicator), 57cobalt labelled vitamin B12 (ileal indicator), and sulphasalazine (caecal-colonic indicator)) in relation to simultaneously ingested 51CrEDTA. Five normal controls, six patients with untreated coeliac disease, five with Crohn's ileitis, and five with pan-ulcerative colitis underwent study, which entailed the simultaneous ingestion of the above four test substances followed, during the next 24 hours, by timed serial collection of urine and serum for marker analysis. Urinary excretion of 51CrEDTA was significantly increased in all patient groups. Analysis of serum appearances and profiles of the markers suggested that the increased intestinal permeation of 51CrEDTA took place in the diseased jejunum in patients with coeliac disease, predominantly in the ileum in Crohn's disease and in the colon in the patients with pan-ulcerative colitis. A new non-invasive technique has been assessed that permits the localisation of the site of permeability changes with the gastrointestinal tract.

Intestinal permeability changes in response to acetylsalicylic acid in relatives of patients with Crohn's disease

BACKGROUND & AIMS: Presence of a familial intestinal permeability defect in Crohn's disease remains controversial despite numerous studies. The purpose of this study was to determine whether detection of a permeability defect in first-degree relatives of patients with Crohn's disease can be enhanced using an acetylsalicylic acid provocation test. METHODS: Lactulose-mannitol ratio, a measure of intestinal permeability, and total sucrose excretion, a measure of gastroduodenal permeability, were determined before and after ingestion of acetylsalicylic acid in healthy controls, in patients with Crohn's disease, and in the first-degree relatives of patients with Crohn's disease. Subjects were classified as hyperresponders if their results were above the mean of + 2SD of the controls. RESULTS: First-degree relatives had a 110% increase in intestinal permeability after acetylsalicylic acid compared with an increase of 57% in controls (P = 0.001). Thirty-five percent of relatives were classified as hyperresponders. There was no significant difference in the change in sucrose excretion between relatives and controls (259% vs 198%; P < 0.05). CONCLUSIONS: First-degree relatives of patients with Crohn's disease have an exaggerated increase in intestinal but not gastroduodenal permeability in response to acetylsalicylic acid. This study supports a familial permeability defect in Crohn's disease, which may not be present in all families. (Gastroenterology 1996 May;110(5):1395-403)

INTESTINAL PERMEABILITY IN CHILDREN WITH FOOD ALLERGY

We evaluated intestinal permeability in children with food allergy by the measurement of lactulose/L-rhamnose urinary excretion ratio (L/R ratio) after orally loaded lactulose (a disaccharide) and L-rhamnose (a monosaccharide).The mean L/R ratio in food-allergic patients restricted major offending foods (eggs and cow's milk) partially was significantly higher than in those restricted major offending foods strictly (p<0.01). Furthermore, the mean L/R ratio in patients restricted major offending foods strictly was comparable with that in healthy subjects (controls). Individual changes in intestinal permeability were also evaluated after elimination diets and after oral food challenges. The mean L/R ratio decreased significantly after elimination diets (p<0.05) and increased significantly after the positive food challenges (p<0.05) in patients with food allergy.In non-atopic children suffering from respiratory infections during the previous 10 days, the mean L/R ratio was significantly higher than that in controls (p<0.05).In conclusion, the measurement of lactulose/L-rhamnose excretion ratio was useful to evaluate alterations in the mucosal barrier function under elimination diet and food antigens intake.

Assessment of intestinal permeability changes induced by nonsteroidal anti-inflammatory drugs in the rat

Intestinal permeability was investigated as an alternative to intestinal ulceration for measuring nonsteroidal anti-inflammatory drug (NSAID) gut damage in the rat and developed as a method for routine measurement. NSAID dose-response curves produced using the two indices of damage showed that intestinal permeability is as sensitive and reproducible as ulceration, although changes could not be detected before visible ulceration occurred. Lactulose, [ 51Cr]-EDTA and [ 14C]-carboxyinulin were compared as possible in vivo markers of rat intestinal permeability. Measurement of [ 51Cr]-EDTA permeation was found to be the most sensitive and reproducible method. Dose-response curves produced by measuring [ 51Cr]-EDTA permeation were used to compare the potency of the two NSAIDs piroxicam and (S+)-ibuprofen; piroxicam was found to be 10 times more potent in increasing intestinal permeability than (S+)-ibuprofen. These studies show that intestinal permeability measurement is a useful alternative to other methods of assessing NSAID adverse effect and is easily and rapidly performed.

Nonsteroidal Anti-Inflammatory Drug-Induced Enteropathy: Case Discussion and Review of the Literature

Nonsteroidal Anti-Inflammatory Drug-Induced Enteropathy: Case Discussion and Review of the Literature

Effect of Escherichia coli enterotoxins on macromolecular absorption.

Macromolecular absorption of gliadin, a wheat protein and alpha lactalbumin, a milk protein was evaluated in control and Escherichia coli enterotoxin (heat-stable, heat-labile, and both heat-stable and heat-labile enterotoxin) treated mice. The peak concentration of gliadin and lactalbumin was two hours and three hours after their ingestion, respectively. There was also a significant increase (p < 0.01) in the absorption of both the proteins in all the three toxin treated groups compared with the control group. These results suggest that intestinal permeability and macromolecular absorption changes after E coli infection.

Effect of disodiumcromoglycate on intestinal permeability changes and clinical response during cow's milk challenge

Oral disodiumcromoglycate (DSCG) has been used for many years in the prevention of food allergic reactions. The reported effectiveness varies widely and little is known about the mode of action. The aim of this study was to evaluate the effect of DSCG pretreatment (2 x 100 mg) on intestinal permeability (IP), as measured with a sugar absorption test (SAT), in relation to the clinical response during food challenge in 30 children suspected of cow's milk allergy. In the SAT the urinary Lactulose/Mannitol (L/M) ratio was measured after oral administration of these compounds. DSCG pretreatment did not alter the number of clinically positive challenges. Children with clinically positive challenges showed a significant increase in the L/M ratio with placebo pretreatment as compared to children with clinically negative challenges (p = 0.0008). This difference was reduced to nonsignificant levels after DSCG pretreatment (p = 0.07). We conclude that DSCG in this dosage probably reduces the local intestinal response but does not prevent the extraintestinal reactions.

Effect of Diosmectite on Intestinal Permeability Changes in Acute Diarrhea

The effect of diosmectite on intestinal permeability changes in acute diarrhea was measured during a double‐blind placebo‐controlled trial carried out in 59 Gabonese children aged 5–35 months. Intestinal permeability tests (IPTs), measuring the urinary elimination of orally administered lactulose and mannitol at a dosage of 1 g/10 kg each, were performed during the morning following admission and repeated 2 days later after treatment by diosmectite or placebo. During the first IPT, urine volume and lactulose and mannitol urinary recoveries were comparable in the diosmectite and in the placebo groups: 50 vs. 35.5 ml (median; p = 0.21), 1.01 vs. 1.27% (p = 0.35), and 2.20 vs. 2.87% (p = 0.12). As a result, the lactulose/mannitol (L/M) ratio was similar in the two groups: 44.44 vs. 35.33% (p = 0.98). During the second IPT, the urinary lactulose recovery decreased similarly in both groups (‐0.18 vs. −0.29%; p = 0.76), whereas the urinary mannitol recovery exhibited opposite variations, the increase in the diosmectite group (+1.43%) contrasting significantly with the decrease in the placebo group (‐0.47%; p = 0.01). When comparing the first and the second IPT, the decrease of the L/M ratio was significant in the diosmectite group (44.44 vs. 28.32%; p = 0.02) and not in the placebo group (35.33 vs. 48.23%; p = 0.91). During gastroenteritis, diosmectite appears to enhance absorption of mannitol, a marker of intestinal absorptive area.

Effect of aging and caloric restriction on intestinal permeability

Intestinal permeability is increased in several disorders such as Crohn's disease or rheumatoid arthritis. Since aging leads to alteration of many biological functions, the effect of aging on intestinal permeability was studied by measuring the intestinal permeability in aging rats gavaged with different size permeability probes— mannitol, polyethylene glycol (PEG) 400, and inulin. In rats fed with control diet, there was a significant increase in intestinal permeability to medium size probes PEG 400 (14.8 ± 0.4 and 21.0 ± 1.1% at 3 and 28 months respectively, p < .01) and mannitol (3.41 ± 0.4 and 5.3 ± 0.5% at 3 and 28 months, respectively, p < .01). Intestinal permeability of the large macromolecule inulin did not change (0.42 ± 0.03 and 0.38 ± 0.02% at 3 and 28 months, respectively) with aging. There was no correlation between weight of the rats and their intestinal permeability. Because dietary caloric restriction has been found to prolong the life span, retard deterioration of several biological functions, and affect intestinal absorptive functions, we examined the effect of lifelong calorie restriction on intestinal permeability changes. Lifelong calorie-restricted diet did not affect age-related change in intestinal permeability. We conclude that intestinal permeability of medium size probes increases with aging and that lifelong caloric restriction does not prevent this change. We speculate that age-associated deterioration in intestinal barrier functions could permit increased systemic absorption of lumenal antigens and could perhaps contribute to the genesis of antigen-related age-associated diseases.

Identical intestinal permeability changes in children with different clinical manifestations of cow's milk allergy

To determine the relationship between clinical symptoms of cow's milk allergy (CMA) and intestinal permeability, 51 children (mean age, 13 months) were studied during a diagnostic milk provocation test. Intestinal permeability was assessed by orally administered lactulose (4 gm) and mannitol (0.8 gm) immediately before (day 0) the milk challenge and 3 days later (day 3). Twenty-four patients evinced cutaneous symptoms and 27, gastrointestinal symptoms. The mean (95% confidence interval) urinary lactulose/mannitol recovery ratios before the milk challenge were, in both groups of patients, comparable to the level of that of control patients, 0.02 (0.01 and 0.03). A rise in lactulose/mannitol excretion ratios followed cow's milk administration by day 3 in patients with skin symptoms, 0.06 (0.03 and 0.13), as well as in patients with gastrointestinal symptoms, 0.08 (0.04, 0.17). These levels were significantly different from the control level, p = 0.003, and the prechallenge level, p = 0.01. This difference was caused by a concomitant increase in urinary recovery of lactulose and a decrease of mannitol. These results indicate that the intestinal barrier is equally altered in patients with different clinical manifestations of CMA and further suggest that enhancement of mucous membrane permeability is not a primary defect in the pathogenesis of CMA but rather a secondary phenomen, possibly caused by a hypersensitivity reaction in the intestinal mucosa.

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.