Intestinal permeability in patients with Crohn's disease and their first degree relatives.

It has been reported that intestinal permeability to polyethylene glycol 400 is increased in patients with Crohn's disease and their apparently unaffected first degree relatives. Because of the implications that these findings have for the aetiology of Crohn's disease these studies were repeated. Patients with Crohn's disease (n = 28) and 32 first degree relatives from 11 families underwent a polyethylene glycol 400 (PEG400) intestinal permeability test and a hyperosmotic (1500 mosmol/l) absorption/permeability test using 3-0-methyl-D-glucose, D-xylose, L-rhamnose, lactulose, and 51chromium labelled ethylenediamine-tetraacetate. The five hour urine excretion of polyethylene glycol 400 did not differ significantly between controls (n = 25) and first degree relatives, 25.5 (3.3)% v 24.6% (4)% (mean(SD)) p greater than 0.1, respectively. Patients with small bowel involvement excreted significantly less (p less than 0.01) polyethylene glycol 400 (16.3 (4.6)% than controls while those with Crohn's colitis did not (26.4 (3.9)% p greater than 0.1). The permeation of the monosaccharides in patients with Crohn's disease and their first degree relatives did not differ from normal subjects. The permeation of lactulose and 51chromium ethylenediaminetetraacetate was not significantly altered in first degree relatives but was significantly increased in the patients, as was the lactulose/L-rhamnose urine excretion ratio which is a specific measure of small intestinal permeability. These studies show normal absorption and permeability in first degree relatives of patients with Crohn's disease. A genetically determined abnormality of intestinal permeability is not likely to be an important aetiological factor in Crohn's disease.     

Histopathology of Crohn's Disease

The relationships among intestinal permeability, advancing human immunodeficiency virus (HIV) infection, and the presence of diarrhoea or weight loss were investigated in 51 HIV patients and 20 healthy controls. Ten patients with untreated coeliac disease were also investigated for comparison. Fasting subjects drank an isosmolar test solution containing D-xylose, lactulose (LL), L-rhamnose (R) and 3-O-methyl-D-glucose. Urine was collected for 5 h, test sugar content being subsequently measured by thin-layer chromatography for the dosing sugars. Intestinal permeability (LL/R excretion ratio) and recovery of D-xylose and 3-O-methyl-D-glucose in urine were abnormal in patients with HIV disease, and especially those with diarrhoea, as they were in coeliac disease. Patients with coeliac disease and HIV disease, especially when diarrhoea and/or weight loss were present, had significantly reduced 5-h excretion of L-rhamnose, D-xylose, and 3-O-methyl-D-glucose. These data indicate that abnormal permeability and reduced intestinal absorption capacity are common in HIV patients, occur at all stages of HIV disease, especially in the presence of diarrhoea, and, with the exception of lactulose permeation, are relatively similar to the alterations seen in coeliac disease.     

Simultaneous Administration of Lactulose and 51Cr-Ethylenediaminetetraacetic Acid: A Test to Distinguish Colonic from Small-Intestinal Permeability Change

In normal adults intestinal permeation of ingested ⁵¹Cr-ethylenediaminetetraacetic acid (EDTA) is greater than that of lactulose. This difference is abolished in patients with ileostomies, suggesting that it results from colonic permeation of ⁵¹Cr-EDTA, which, unlike lactulose, resists bacterial degradation. to investigate the effect of an increase in colonic permeability on absorption of the two molecules, lactulose (5 g) and ^5ICr-EDTA (50 μCi) were given orally in isosmolar solution to 11 patients with colitis, and their 24-h urinary excretion measured. By comparison the effect of an increase in small-intestinal permeability induced by ingestion of a hyperosmolar solution (4240 mosm/1) was measured in 10 healthy adults. Hyperosmolar stress increased the 24-h urinary excretion of ⁵¹Cr-EDTA above the normal mean + 2 standard deviations (3.31%) in ail 10 healthy subjects, and in all of these excretion of lactulose was also increased (>1.06%). In contrast, although seven colitics had a urinary excretion of “Cr-EDTA above the normal mean + 2 SD, in only two of these patients was recovery of lactulose increased. This suggests that simultaneous administration of lactulose and ⁵¹Cr-EDTA may enable permeability changes affecting the colon alone to be distinguished from those involving the small intestine.     

Do non-steroidal anti-inflammatory drugs increase colonic permeability?

Urinary excretion of orally administered lactulose and 51 chromium labelled ethylenediamine tetra-acetate (51Cr-EDTA) was measured in 12 healthy adult subjects and in six patients with ileostomies to assess intestinal permeability. In normal subjects, 24 hour urinary recovery of 51Cr-EDTA was significantly greater than that of lactulose (mean (SEM) 2.27 (0.15) v 0.50 (0.08)% oral dose; p less than 0.001), but in ileostomy patients recovery of the two markers was the same. In normal subjects, therefore, the difference between the two markers may arise from bacterial break-down of lactulose but not of 51Cr-EDTA in the distal bowel, urinary excretion of lactulose representing small intestinal permeation and that of 51Cr-EDTA representing both small and large intestinal permeation. The markers were then given simultaneously to nine patients receiving non-steroidal anti-inflammatory drugs (NSAIDs) for rheumatoid arthritis and osteoarthritis. The 24 hour urinary recovery of 51Cr-EDTA in the patients was significantly greater than normal (4.64 (1.20) v 2.27 (0.15)% oral dose; p less than 0.01), but that of lactulose was not significantly affected. Moreover, the increase in 51Cr-EDTA recovery was most noticeable in the later urine collections. Both of these findings suggest that NSAIDs may increase colonic permeability.     

Editorial: The North-to-South Gradient of Hepatitis C Virus Infection

Background: We earlier compared the lactulose/mannitol and ⁵¹Cr-ethylenediaminetetraacetic acid (EDTA)/¹⁴C-mannitol methods for intestinal permeability We have now investigated an increased number of control subjects, with special regard to the influence of urinary volume, sex, age, and smoking on marker excretion, and patients with intestinal disorders, with special regard to correlations between markers. Methods: The 0- to 6-h urinary excretion of orally administered markers was measured in 65 control subjects and in 70 patients. Results: In the control group excretion of mannitol and ¹⁴C-mannitol (small-pore permeability markers) was strongly correlated to urinary volume, whereas such correlation was weak for lactulose and absent for ^5lCr-EDTA (large-pore permeability markers). No sex difference in marker excretion was found, but correlation to urinary volume was more pronounced in males. There was a slightly decreasing excretion of markers with increasing age, reaching significance for ^5lCr-EDTA and ^l4C-mannitol; their excretion ratio was unaffected. Smoking did not significantly affect marker excretion. In the patient group the excretion of large-pore markers tended to be higher and that of small-pore markers to be lower than in the control group; correlation between the large-pore markers, between the small-pore markers, and between the large-pore/small-pore marker ratios was higher than in the control group. Conclusions: Correction for urinary volume substantially reduces variability in small-pore marker excretion. Excretion of both types of markers tends to decrease with age, the large-pore/small-pore marker ratio remaining unchanged. Smoking does not affect small-intestinal permeability. ¹⁴C-mannitol is preferred to chemically determined mannitol owing to lower test variability.     

Simultaneous administration of lactulose and 51Cr-ethylenediaminetetraacetic acid. A test to distinguish colonic from small-intestinal permeability change.

In normal adults intestinal permeation of ingested 51Cr-ethylenediaminetetraacetic acid (EDTA) is greater than that of lactulose. This difference is abolished in patients with ileostomies, suggesting that it results from colonic permeation of 51Cr-EDTA, which, unlike lactulose, resists bacterial degradation. To investigate the effect of an increase in colonic permeability on absorption of the two molecules, lactulose (5 g) and 51Cr-EDTA (50 microCi) were given orally in isosmolar solution to 11 patients with colitis, and their 24-h urinary excretion measured. By comparison the effect of an increase in small-intestinal permeability induced by ingestion of a hyperosmolar solution (4240 mosm/l) was measured in 10 healthy adults. Hyperosmolar stress increased the 24-h urinary excretion of 51Cr-EDTA above the normal mean + 2 standard deviations (3.31%) in all 10 healthy subjects, and in all of these excretion of lactulose was also increased (greater than 1.06%). In contrast, although seven colitics had a urinary excretion of 51Cr-EDTA above the normal mean + 2 SD, in only two of these patients was recovery of lactulose increased. This suggests that simultaneous administration of lactulose and 51Cr-EDTA may enable permeability changes affecting the colon alone to be distinguished from those involving the small intestine.     

Assessment of Intestinal Permeability and Absorption in Cirrhotic Patients with Ascites Using Combined Sugar Probes

Gastrointestinal dysfunction in patients with cirrhosis may contribute to complications such as malnutrition and spontaneous bacterial peritonitis. To determine whether cirrhotic patients with ascites have altered intestinal function, we compared intestinal permeability and absorption in patients with liver disease and normal subjects. Intestinal permeability and absorption were investigated in 66 cirrhotic patients (48 with ascites, 18 without ascites) and 74 healthy control subjects. Timed recovery of 3-O-methyl-D-glucose, D-xylose, L-rhamnose, and lactulose in urine following oral administration was measured in order to assess active and passive carrier-mediated, and nonmediated, absorptive capacity, as well as intestinal large-pore/small-pore (lactulose/rhamnose) permeability. Test sugars were measured by quantitative thin-layer chromatography and results are expressed as a percentage of test dose recovered in a 5-h urine collection. Sugar excretion ratios relating to small intestinal permeability (lactulose/rhamnose) and absorption (rhamnose/3-O-methyl-D-glucose) were calculated to avoid the effects of nonmucosal factors such as renal clearance, portal hypertension, and ascites on the recovery of sugar probes in urine. Compared with normal subjects, the mean lactulose/rhamnose permeability ratio in cirrhotic patients with ascites was significantly higher (0.058 vs. 0.037, P < 0.001) but not in cirrhotic patients without ascites (0.041 vs. 0.037). Cirrhotic patients with ascites had significantly lower mean recoveries of 3-O-methyl-D-glucose (23.0 vs. 49.1%; P < 0.001), D-xylose (18.8 vs. 34.5%; P < 0.001), L-rhamnose (4.0 vs. 9.1%; P < 0.001), and lactulose (0.202 vs. 0.337%; P < 0.001) than normal subjects. However, the mean rhamnose/3-O-methyl-D-glucose ratio was the same in cirrhotic patients with ascites as normal subjects (0.189 vs. 0.189), indicating that the reduction in probe recovery was due to nonmucosal factors. Compared with normal subjects, cirrhotic patients with ascites have abnormal intestinal permeability, measured by urinary lactulose/rhamnose excretion, and normal small intestinal absorption, assessed by the urinary rhamnose/3-O-methyl-D-glucose ratio. Low urine recovery of sugar probes found in cirrhotic patients appears to be the result of nonintestinal factors affecting clearance rather than reduced intestinal absorption.     

Bile-Induced Chronic Gastric Ulcer in Swine with Excised Oxyntic Gland Area

Background: An increased intestinal permeability (IP) may be a pathogenetic factor in Crohn disease (CD). Increases in IP could be an indicator of subclinical disease and precede clinical relapses. We examined whether an increased IP is a valid predictor of relapse in CD. Methods: 27 patients with CD in remission (CDAI &lt;150) and 22 healthy controls ingested 3.7 MBq of ⁵¹Cr-EDTA, 20 kBq of ¹⁴Cmannitol and 5 g of unlabelled mannitol in 100 ml of distilled water. The percent urine excretion (24 h) of labelled markers was determined. Patients were followed for 1 year or until relapse, defined as CDAI &gt; 150 and &gt; 50 from baseline. Results: Median (25th-75th percentiles). The excretion of ⁵¹Cr-EDTA was 1.55% (1.13%-2.53%) for patients and 1.20% (1.11%-1.44%) for controls (P = 0.04). Three of 9 patients with a raised, and 6 of 18 patients with a normal, ⁵¹Cr-EDTA excretion relapsed (P = 1.00; Fisher's exact test). Thus, the specificity and sensitivity of the ⁵¹Cr-EDTA test as a predictor of relapse was 33% and 33%, respectively. The ⁵¹Cr-EDTA/¹⁴C-mannitol index was 0.060 (0.037-0.093) for patients and 0.045 (0.038-0.054) for controls (P = 0.06). Four of 12 patients with a raised, and 5 of 15 patients with a normal, index relapsed (P = 1.00; Fisher's exact test). Thus, the specificity and sensitivity of the index test as a predictor of relapse was 33% and 44%, respectively. For controls and patients in remission, who were tested twice, variability of and fluctuations in both the ⁵¹Cr-EDTA excretion and the index were greatest for patients. Conclusions: This study supports previous findings of an increased IP in patients with CD. Although fluctuations in the permeation of markers were pronounced in CD, neither the excretion of ⁵¹Cr-EDTA nor the ⁵¹Cr-EDTA/¹⁴C-mannitol index test were valid predictors of relapse in CD.     

Detection of Naproxen-Induced Intestinal Permeability Change May Be Facilitated by Adding a Standardized Meal but Not by Forming Marker Ratios

Background: We recently compared the intestinal permeability markers polysucrose (PS) 15000, ⁵¹Cr-ethylenediaminetetraacetic acid (EDTA), and ¹⁴C-mannitol in healthy humans. We have now studied the ability of these markers to show non-steroidal anti-inflammatory drug (NSAID)-induced intestinal damage, with special regard to the possibility of improving discrimination versus healthy intestine by using a hyperosmolar test solution, adding a standardized liquid meal, calculating paracellular/transcellular marker excretion ratios, or correcting excretion values for urinary volume. Methods: Seventeen healthy volunteers ingested a solution containing PS 15000, ⁵¹Cr-EDTA, and ¹⁴C-mannitol before and after 1 week of naproxen intake, the solution being isosmolar, hyperosmolar, or isosmolar and followed by a standardized liquid meal. Fractional urinary excretion of the substances was measured over 0–4 h, 4–8 h, and 8–12 h. Results: The excretion of the paracellular permeability markers PS 15000 and ⁵¹Cr-EDTA increased after NSAID pretreatment, whereas that of the transcellular marker ¹⁴C-mannitol was unaffected. A standardized liquid meal reduced test variability for all markers and tended to improve differentiation between diseased and healthy intestine. A hyperosmolar test solution tended to improve differentiation for ⁵¹Cr-EDTA but not for PS 15000. Calculating a paracellular/transcellular ratio or correcting excretion values for urinary volume did not improve the differentiation. Conclusions: A standardized liquid meal may improve the capacity of permeability tests to distinguish between healthy and NSAID-damaged intestine.     

In vivo influence of nicotine on human basal and NSAID-induced gut barrier function

BACKGROUND: Smoking reduces the non-steroidal anti-inflammatory drug (NSAID)-induced small intestinal permeability increase in healthy people. It also affects inflammatory bowel disease that is associated with a disturbed gut barrier function. To assess the role of nicotine on barrier function, its influence on basal and NSAID-induced intestinal permeability was studied in healthy volunteers. METHODS: Thirty-one healthy non-smoker subjects performed permeability tests with 51Cr-EDTA and sugar markers (sucrose, lactulose, mannitol, sucralose) before and during 2 weeks of nicotine patch application, and with and without indomethacin intake, respectively. Since smoking has been described as affecting motility, transit measurements were also done with the sodium[13C]-octanoate and lactose-[13C]-ureide breath tests before and during nicotine exposure. Correlations between permeability markers were checked and the influence of gastrointestinal transit was assessed. RESULTS: Nicotine did not affect barrier function in vivo, nor gastric emptying, small-bowel transit time or orocaecal transit. 51Cr-EDTA and lactulose correlated in basal 0-6 h permeability testing (r = 0.529, P < 0.0001), as did 6-24 h excretion of 51Cr-EDTA and sucralose (r = 0.474, P < 0.001); 97% and 90% of the subjects had a permeability increase after indomethacin intake for 0-6 h and 6-24 h excretion of Cr-EDTA, respectively. This population proportion is 63% for lactulose/mannitol and 83% for sucralose. CONCLUSIONS: Short-term exposure to nicotine does not alter normal basal or NSAID-induced gut barrier function or transit. 51Cr-EDTA and the respective sugar markers correlate well in in vivo permeability testing in healthy humans. The radioactive test detects more NSAID-induced permeability increase than does the lactulose/mannitol ratio permeability test.     

Intestinal permeability in patients with coeliac disease and dermatitis herpetiformis

Intestinal permeability was investigated in patients with coeliac disease and dermatitis herpetiformis by a 51Chromium-labelled ethylenediaminetetraacetate (51Cr-EDTA) absorption test and the results correlated with histomorphometric analysis and intraepithelial lymphocyte counts of jejunal biopsies. The mean (+/- SD) 24 hour urine excretion of 51Cr-EDTA in 34 healthy volunteers was 1.9 +/- 0.5% of the orally administered test dose. Patients with untreated coeliac disease (19) or untreated dermatitis herpetiformis (five) excreted significantly more 51Cr-EDTA than controls (5.9 +/- 2.7% and 4.6 +/- 2.1%, respectively, p less than 0.001) and all were outside the normal range of 1.0-2.6%. Patients with coeliac disease (42) treated for 6 months-23 years (mean 5 years) and patients with dermatitis herpetiformis (11) treated for 6 months-8 years (mean 3 years) excreted significantly more 51Cr-EDTA than controls, 4.2 +/- 2.4% p less than 0.0001 and 3.0 +/- 0.9% p less than 0.003 respectively. Eleven of 14 (79%) treated patients with coeliac disease with an entirely normal jejunal mucosae demonstrated abnormal intestinal permeability. Intestinal permeability did not correlate significantly with either the mucosal height/crypt depth ratio or intraepithelial lymphocyte counts in jejunal biopsies from patients with untreated or treated coeliac disease. The demonstration of a persistent increase in intestinal permeability in patients with both coeliac disease and dermatitis herpetiformis may suggest a common pathogenetic mechanism in both disorders. It is postulated that altered permeability may facilitate the entry of gluten or a fraction thereof into the lamina propria where it causes a cascade of immunological events.     

Comparison of Polysucrose 15000, 51Cr-labelled Ethylenediaminetetraacetic Acid,and 14C-Mannitol as Markers of Intestinal Permeability in Man

Background: We recently reported increased intestinal permeability to polysucrose (PS) 15000 in patients with Crohn's disease and in patients treated with non-steroidal anti-inflammatory drugs (NSAIDs). We have now compared this new macromolecular marker (14,700 D) with the conventional markers, ⁵¹Cr-labelled ethylenediaminetetraacetic acid (EDTA) (342 D) and ⁴¹C-mannitol (182 D), in healthy humans.

Methods: Twenty healthy volunteers on four occasions ingested a solution containing PS 15000, ⁵¹Cr-EDTA, and ¹⁴C-mannitol, the test solution being, respectively, isoosmolar, hyperosmolar, isoosmolar followed by a standard meal, and isoosmolar after 1 week of NSAID treatment. Fractional urinary excretion of the substances was measured over 0–4 h, 4–8 h, and 8–12 h.

Results: The excretion of PS 15000 was, like that of ⁵¹-EDTA but unlike that of ¹⁴C-mannitol, increased by NSAID pretreatment, little affected by hyperosmolar test solution, little correlated to urinary volume, and skew with regard to frequency distribution. Desite being nominally about 40 times lower, the excretion of PS 15000 was highly correlated to that of Cr-EDTA but not to that of ¹⁴C-mannitol. A standard meal reduced the test variability for all three probes.

Conclusions: PS 15000 may be an alternative to ⁵¹Cr-EDTA as a small-intestinal permeability marker. Inclusion of a standard meal reduces test variability.     

The Effect of Ingested Lactulose on Absorption of L-Rhamnose,D-Xylose,and 3-O-Methyl-D-Glucose in Subjects with Ileostomies

Jenkins AP, Menzies IS, Nukajam WS, Creamer B. The effect of ingested lactulose on absorption of L-rhamnose, D-xylose. and 3-O-methyl-D-glucose in subjects with ileostomies. Scand J Gastroenterol 1994;29:820-825.

Background: We have previously shown that small oral doses of poorly absorbed solute can significantly reduce absorption of test sugars in normal volunteers. To confirm these results and investigate the underlying mechanism, the effects of lactulose on absorption of three test sugars in subjects with ileostomies were studied. Methods: Ten fasted subjects with ileostomies ingested an isosmolar test solution containing 2.5g 3-O-methyl-D-glucose, 5.0g D-xylose, 1.0g L-rhamnose, and 50μCi ⁵¹Cr-labelied ethylenediaminetetraacetic acid together with a blue dye transit marker. Urine was collected for time periods of 0-5 h and 5-24 h, to measure excretion of absorbed sugars, and ileostomy effluent was saved from 0-5 h and from 5 h until blue dye transit marker was no longer present, to measure small-bowel output of unabsorbed sugars. After 1 week the test was repeated, including 5 g lactulose in the test solution. Results: Inclusion of lactulose in the test solution significantly reduced the 5 h and 24 h urine excretion of l -rhamnose and D-xylose but not that of 3-O-methyl-D-glucose and increased 0- to 5-h and total ileostomy output of L-rhamnose and D-xylose but not of 3-O-methyl-D-glucose. The presence of lactulose also reduced the time for first appearance of the blue dye transit marker in the effluent and increased effluent volume together with output of electrolyte. Conclusion: Poorly absorbed solute reduces intestinal absorption by retention of fluid and electrolyte, with subsequent intraluminal dilution and acceleration of transit.     

Abnormal intestinal permeability to sugars in diabetes mellitus

Summary A test of intestinal mucosal function which utilizes the differential permeability of L-rhamnose and lactulose has been reported to be helpful in the diagnosis of gluten-sensitive enteropathy. We have applied this test to 48 male subjects with diabetes mellitus to evaluate its usefulness as a screening test in diabetic patients and to further study sugar absorption in these individuals. Total urinary lactulose excretion in the 13 healthy control subjects was 54.5 ± 8.5 mg/5 h, while excretion by diabetic patients was increased at 116.1 ± 15.7 mg/5 h (p < 0.01). Similarly, total L-rhamnose excretion by diabetic patients was significantly higher (139.7 ± 14.3 mg/5 h vs 84.3 ± 18.4 mg/5 h, p<0.05). The ratio of percent urinary excretion for lactulose/L-rhamnose (L/R ratio) for diabetic patients (0.197 ± 0.024) was not different from the control subjects (0.151 ± 0.2). Nine out of 48 diabetic patients studied had lactulose/L-rhamnose ratios higher than the mean plus two standard deviations of the control group, which might lead to the diagnosis of small bowel mucosal disease. Although we may have been detecting subclinical mucosal disease or gluten sensitive enteropathy in a subgroup, it appears that this test of intestinal mucosal function should be interpreted with caution in diabetic patients.     

Relationship between Small-Intestinal Transit Rate and Intestinal Absorption of 14C-labelled Mannitol and 51Cr-labelled Ethylenediaminetetraacetic Acid in Healthy Subjects

Background: Although the small-intestinal transit rate is generally considered to influence the urinary excretion of markers of intestinal permeability, no study has until now formally addressed the importance of this influence in humans. Methods: Ten healthy subjects ingested a test solution containing ^99mTc-labelled diethylenetriaminepentaacetic acid (^99mTc-DTPA), ¹⁴C-labelled mannitol (¹⁴C-mannitol), and ⁵¹Cr-labelled ethylenediaminetetraacetic acid (⁵¹Cr-EDTA). After ingestion, the small-intestinal transit rate of ^99mTc-DTPA was measured with the gamma camera technique. Urine was collected for time periods of 0–2 h, 2–4 h, and 4–6 h to measure the excretion of absorbed ¹⁴C-mannitol and ⁵¹Cr-EDTA. Moreover, the distribution volume and plasma clearance of ¹⁴C-mannitol and ⁵¹Cr-EDTA were determined in each subject. Results: A positive correlation was found between mean small-intestinal transit time and 0- to 6-h urinary excretion of ¹⁴C-mannitol. The study did not show any correlation between small-intestinal transit rate and 0- to 6-h urinary excretion of ⁵¹Cr-EDTA. Urinary excretion of neither ¹⁴C-mannitol nor ⁵¹Cr-EDTA was affected by distribution volume or urine volume. A positive correlation was observed between plasma clearance and 0- to 6-h urinary excretion of ¹⁴C-mannitol, whereas plasma clearance did not influence the urinary excretion of ⁵¹Cr-EDTA. Conclusions: Small-intestinal transit rate seems to have a significant effect on 0- to 6-h urinary excretion of ¹⁴C-mannitol, whereas small-intestinal transit rate does not influence the timed urinary excretion of ⁵¹Cr-EDTA.     

The Effect of Polyacrylic Acid Polymers on Small-Intestinal Function and Permeability Changes Caused by Indomethacin

Non-steroidal anti-inflammatory drug (NSAID)-induced increased small-intestinal permeability appears to be a prerequisite for the development of NSAID enteropathy, which is a cause of much morbidity in patients with rheumatoid arthritis. We assessed, with a combined absorption-permeability test, the effects of Carbopol® (a polyacrylic acid polymer capable of increasing mucus strength and viscosity) on intestinal function and whether it protected against indomethacin-induced increased intestinal permeability. Using a test solution of 3-0-methyl-D-glucose, D-xylose, L-rhamnose, and ⁵¹Cr-labelled ethylenediaminetetraacetic acid with 5-h urine collections for marker analyses, we tested 16 subjects, as base line, after 20 ml Carbopol 4 times daily for 4 days, after indomethacin alone (75 + 75 mg), and after coadministration of Carbopol and indomethacin. Carbopol had no significant effect on the permeation or absorption of the test substances. Indomethacin increased intestinal permeability significantly, and this was unaffected when Carbopol was coadministered with indomethacin, showing that Carbopol does not limit the immediate damage of NSAIDs on the small intestine.     

Increased Intestinal Marker Absorption Due to Regional Permeability Changes and Decreased Intestinal Transit during Sepsis in the Rat

Wang Q, Pantzar N. Jeppsson B, Weström BR, Karlsson BW. Increased intestinal marker absorption due to regional permeability changes and decreased intestinal transit during sepsis in the rat. Scand J Gastroenterol 1994;29:1001-1008.

Background: The intestinal barrier properties are impaired during inflammation and sepsis, but the mechanisms behind this are unknown and were therefore investigated during experimental sepsis in rats.

Methods: The different-sized intestinal absorption markers ⁵¹Cr-labeled ethylenediaminetetraacetic acid (EDTA) and ovalbumin were gavaged to rats made septic by intra-abdominal bacterial implantation and to sham-operated rats. Regional tissue permeability was measured in diffusion chambers, and intestinal transit was evaluated by intestinal accumulation of gavaged ⁵¹Cr-EDTA.

Results: In comparison with the sham-operated rats, septic rats had higher ⁵¹Cr-EDTA levels in blood and urine and showed a prolonged intestinal transit. Septic rats also had a lower tissue permeability to both markers in the small intestines but higher permeability to ovalbumin in the colon. Rats receiving morphine to decrease intestinal motility showed similar changes, with a decreased intestinal transit and increased marker absorption.

Conclusions: The results suggest that the increased intestinal absorption during sepsis was due to regional permeability changes and prolonged intestinal transit.     

Is an increased intestinal permeability a valid predictor of relapse in Crohn disease?

BACKGROUND: An increased intestinal permeability (IP) may be a pathogenetic factor in Crohn disease (CD). Increases in IP could be an indicator of subclinical disease and precede clinical relapses. We examined whether an increased IP is a valid predictor of relapse in CD. METHODS: 27 patients with CD in remission (CDAI <150) and 22 healthy controls ingested 3.7 MBq of 51Cr-EDTA, 20 kBq of 14C-mannitol and 5 g of unlabelled mannitol in 100 ml of distilled water. The percent urine excretion (24 h) of labelled markers was determined. Patients were followed for 1 year or until relapse, defined as CDAI > 150 and > 50 from baseline. RESULTS: Median (25th-75th percentiles). The excretion of 51Cr-EDTA was 1.55% (1.13%-2.53%) for patients and 1.20% (1.11%-1.44%) for controls (P = 0.04). Three of 9 patients with a raised, and 6 of 18 patients with a normal, 51Cr-EDTA excretion relapsed (P = 1.00; Fisher's exact test). Thus, the specificity and sensitivity of the 51Cr-EDTA test as a predictor of relapse was 67% and 33%, respectively. The 51Cr-EDTA/14C-mannitol index was 0.060 (0.037-0.093) for patients and 0.045 (0.038-0.054) for controls (P = 0.06). Four of 12 patients with a raised, and 5 of 15 patients with a normal, index relapsed (P = 1.00; Fisher's exact test). Thus, the specificity and sensitivity of the index test as a predictor of relapse was 56% and 44%, respectively. For controls and patients in remission, who were tested twice, variability of and fluctuations in both the 51Cr-EDTA excretion and the index were greatest for patients. CONCLUSIONS: This study supports previous findings of an increased IP in patients with CD. Although fluctuations in the permeation of markers were pronounced in CD, neither the excretion of 51Cr-EDTA nor the 51Cr-EDTA/14C-mannitol index test were valid predictors of relapse in CD.     

Intestinal permeability and bacterial growth of the small bowel in patients with primary sclerosing cholangitis

Objective. Animal studies show that small intestinal bacterial overgrowth and infusion of bacterial antigens into portal blood cause hepatic histological changes similar to those seen in primary sclerosing cholangitis in man. It has been suggested that a similar mechanism involving bacterial overgrowth with increased small-bowel permeability may play a pathogenic role in patients with primary sclerosing cholangitis.Material and methods. Twenty-two patients with primary sclerosing cholangitis (13 M, 9 F, median age 37 years, range 21–74 years), 19 of whom (83%) had quiescent inflammatory bowel disease, were included in the study along with 18 healthy volunteers (9 F, 9 M, median age 36 years, range 23–80 years). Small-bowel bacterial overgrowth was defined as the presence of colonic flora >10⁵ colony-forming units (cfu)/ml from duodenal aspirations. Small-bowel intestinal permeability was assessed as the differential urinary excretion of lactulose/L-rhamnose.Results. Bacterial overgrowth was evident in one patient with primary sclerosing cholangitis (4.5%) (Enterobacter) and in none of the controls. Intestinal permeability in patients with primary sclerosing cholangitis (0.034 (0.026–0.041) (median, interquartile range (IQR)) did not differ significantly from that of the controls (0.033 (0.025–0.041).Conclusions. Small intestinal bacterial overgrowth and increased intestinal permeability does not seem to play an important pathogenic role in patients with primary sclerosing cholangitis.     

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

BACKGROUND: The precise site of intestinal permeability changes in patients with coeliac and inflammatory bowel disease is unknown. AIMS: 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. SUBJECTS: 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. RESULTS: 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. CONCLUSION: A new non-invasive technique has been assessed that permits the localisation of the site of permeability changes with the gastrointestinal tract.