• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of gutGutView this articleSubmit a manuscriptReceive email alertsContact usBMJ
Gut. Oct 1994; 35(10): 1404–1408.
PMCID: PMC1375014

Test conditions greatly influence permeation of water soluble molecules through the intestinal mucosa: need for standardisation.

Abstract

Permeability tests are widely used to investigate the pathogenesis of various gastrointestinal diseases including coeliac disease, infectious diarrhoea, and inflammatory bowel disease. In Crohn's disease they are used as activity parameters by some investigators. Lack of standardisation, however, makes it very difficult to compare data reported in different studies. The aim of this study was to gather permeation data in well controlled test conditions to standardise the methods. Nine healthy volunteers each received five consecutive permeability tests by mouth using polyethylene glycol-400 (PEG-400) and 51Cr-EDTA as probe molecules. The probes were dissolved in water, a glucose solution, a starch solution, a hyperosmolar lactulose-mannitol solution, and a liquid meal. A significantly decreased permeation for both probes was found when given with the hyperosmolar solution. The 51Cr-EDTA permeation was also decreased with water. The permeability index, 51Cr-EDTA/PEG-400, corrected for influencing factors, confirmed that the lactulose-mannitol solution and plain water yield lower values of macro-molecule permeation than starch, glucose or liquid meal. Hyperosmolarity was clearly accompanied by a decrease in permeability probably caused by reversed solvent drag. Interindividual variability of probe permeation and permeability index is very low with a standard liquid meal. It is proposed that for permeability studies a standard liquid meal is always used.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (951K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Chadwick VS, Phillips SF, Hofmann AF. Measurements of intestinal permeability using low molecular weight polyethylene glycols (PEG 400). I. Chemical analysis and biological properties of PEG 400. Gastroenterology. 1977 Aug;73(2):241–246. [PubMed]
  • Cooper BT. Small intestinal permeability in clinical practice. J Clin Gastroenterol. 1984 Dec;6(6):499–501. [PubMed]
  • Teahon K, Smethurst P, Levi AJ, Menzies IS, Bjarnason I. Intestinal permeability in patients with Crohn's disease and their first degree relatives. Gut. 1992 Mar;33(3):320–323. [PMC free article] [PubMed]
  • Jenkins RT, Goodacre RL, Rooney PJ, Bienenstock J, Sivakumaran T, Walker WH. Studies of intestinal permeability in inflammatory diseases using polyethylene glycol 400. Clin Biochem. 1986 Oct;19(5):298–302. [PubMed]
  • Fleming SC, Kynaston JA, Laker MF, Pearson AD, Kapembwa MS, Griffin GE. Analysis of multiple sugar probes in urine and plasma by high-performance anion-exchange chromatography with pulsed electrochemical detection. Application in the assessment of intestinal permeability in human immunodeficiency virus infection. J Chromatogr. 1993 Jun 25;640(1-2):293–297. [PubMed]
  • Krugliak P, Hollander D, Le K, Ma T, Dadufalza VD, Katz KD. Regulation of polyethylene glycol 400 intestinal permeability by endogenous and exogenous prostanoids. Influence of non-steroidal anti-inflammatory drugs. Gut. 1990 Apr;31(4):417–421. [PMC free article] [PubMed]
  • Jenkins AP, Trew DR, Crump BJ, Nukajam WS, Foley JA, Menzies IS, Creamer B. Do non-steroidal anti-inflammatory drugs increase colonic permeability? Gut. 1991 Jan;32(1):66–69. [PMC free article] [PubMed]
  • Lifschitz CH, Mahoney DH. Low-dose methotrexate-induced changes in intestinal permeability determined by polyethylene glycol polymers. J Pediatr Gastroenterol Nutr. 1989 Oct;9(3):301–306. [PubMed]
  • Söderholm J, Olaison G, Sjödahl R, Tagesson C. Smoking and intestinal absorption of oral polyethylene glycols in Crohn's disease. Scand J Gastroenterol. 1993 Feb;28(2):163–167. [PubMed]
  • Aabakken L. Cr-ethylenediaminetetraacetic acid absorption test. Methodologic aspects. Scand J Gastroenterol. 1989 Apr;24(3):351–358. [PubMed]
  • Martines D, Morris AI, Gilmore IT, Williams A, Stockdale H, Critchley M, Smith GA, Billington D. Comparison between the cellobiose/mannitol and 51Cr-labelled ethylenediaminetetra-acetate absorption tests in the detection of coeliac disease. Clin Sci (Lond) 1988 Oct;75(4):375–378. [PubMed]
  • Juby LD, Rothwell J, Axon AT. Lactulose/mannitol test: an ideal screen for celiac disease. Gastroenterology. 1989 Jan;96(1):79–85. [PubMed]
  • Pironi L, Miglioli M, Ruggeri E, Levorato M, Dallasta MA, Corbelli C, Nibali MG, Barbara L. Relationship between intestinal permeability to [51Cr]EDTA and inflammatory activity in asymptomatic patients with Crohn's disease. Dig Dis Sci. 1990 May;35(5):582–588. [PubMed]
  • Andre C, Descos L, Minaire Y. Comparison between lactulose-mannitol test and 51Cr-labelled ethylene diamine tetra-acetate test in inflammatory bowel diseases. Hepatogastroenterology. 1990 Dec;37 (Suppl 2):113–117. [PubMed]
  • Hollander D, Vadheim CM, Brettholz E, Petersen GM, Delahunty T, Rotter JI. Increased intestinal permeability in patients with Crohn's disease and their relatives. A possible etiologic factor. Ann Intern Med. 1986 Dec;105(6):883–885. [PubMed]
  • May GR, Sutherland LR, Meddings JB. Is small intestinal permeability really increased in relatives of patients with Crohn's disease? Gastroenterology. 1993 Jun;104(6):1627–1632. [PubMed]
  • Travis S, Menzies I. Intestinal permeability: functional assessment and significance. Clin Sci (Lond) 1992 May;82(5):471–488. [PubMed]
  • Maxton DG, Bjarnason I, Reynolds AP, Catt SD, Peters TJ, Menzies IS. Lactulose, 51Cr-labelled ethylenediaminetetra-acetate, L-rhamnose and polyethyleneglycol 400 [corrected] as probe markers for assessment in vivo of human intestinal permeability. Clin Sci (Lond) 1986 Jul;71(1):71–80. [PubMed]
  • Hollander D. The intestinal permeability barrier. A hypothesis as to its regulation and involvement in Crohn's disease. Scand J Gastroenterol. 1992 Sep;27(9):721–726. [PubMed]
  • Howden CW, Robertson C, Duncan A, Morris AJ, Russell RI. Comparison of different measurements of intestinal permeability in inflammatory bowel disease. Am J Gastroenterol. 1991 Oct;86(10):1445–1449. [PubMed]
  • Ainsworth M, Eriksen J, Rasmussen JW, Schaffalitzky de Muckadell OB. Intestinal permeability of 51Cr-labelled ethylenediaminetetraacetic acid in patients with Crohn's disease and their healthy relatives. Scand J Gastroenterol. 1989 Oct;24(8):993–998. [PubMed]
  • Philipsen EK, Batsberg W, Christensen AB. Gastrointestinal permeability to polyethylene glycol: an evaluation of urinary recovery of an oral load of polyethylene glycol as a parameter of intestinal permeability in man. Eur J Clin Invest. 1988 Apr;18(2):139–145. [PubMed]
  • Bjarnason I, Smethurst P, Levi AJ, Peters TJ. Intestinal permeability to 51Cr-EDTA in rats with experimentally induced enteropathy. Gut. 1985 Jun;26(6):579–585. [PMC free article] [PubMed]
  • Krugliak P, Hollander D, Ma TY, Tran D, Dadufalza VD, Katz KD, Le K. Mechanisms of polyethylene glycol 400 permeability of perfused rat intestine. Gastroenterology. 1989 Nov;97(5):1164–1170. [PubMed]
  • Madara JL, Pappenheimer JR. Structural basis for physiological regulation of paracellular pathways in intestinal epithelia. J Membr Biol. 1987;100(2):149–164. [PubMed]
  • Pappenheimer JR. Paracellular intestinal absorption of glucose, creatinine, and mannitol in normal animals: relation to body size. Am J Physiol. 1990 Aug;259(2 Pt 1):G290–G299. [PubMed]
  • Fine KD, Santa Ana CA, Porter JL, Fordtran JS. Effect of D-glucose on intestinal permeability and its passive absorption in human small intestine in vivo. Gastroenterology. 1993 Oct;105(4):1117–1125. [PubMed]
  • Elia M, Behrens R, Northrop C, Wraight P, Neale G. Evaluation of mannitol, lactulose and 51Cr-labelled ethylenediaminetetra-acetate as markers of intestinal permeability in man. Clin Sci (Lond) 1987 Aug;73(2):197–204. [PubMed]
  • Jenkins RT, Jones DB, Goodacre RL, Collins SM, Coates G, Hunt RH, Bienenstock J. Reversibility of increased intestinal permeability to 51Cr-EDTA in patients with gastrointestinal inflammatory diseases. Am J Gastroenterol. 1987 Nov;82(11):1159–1164. [PubMed]

Articles from Gut are provided here courtesy of BMJ Group

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Compound
    Compound
    PubChem Compound links
  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...