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Intestinal permeability: the cellobiose/mannitol test
  1. R M CRAIG
  1. Department of Gastroenterology and Hepatology
  2. Northwestern University, Chicago, Illinois 60611, USA
  3. r-craig{at}
  1. Divisione Di Oncologia Medica B
  2. Istituto Nazionale Tumori, via M Semmola
  3. 80131 Napoli, Italy
  4. bdaniele{at}

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Editor,—I should like to bring to your attention a conceptual error in the paper by Danieleet al (OpenUrlCrossRefPubMedWeb of Science) regarding the cellobiose/mannitol test. The authors suggest that improvement in the cellobiose/mannitol ratio reflects improvement in permeability from the use of oral glutamine. However, only mannitol excretion improved significantly with glutamine; cellobiose excretion remained unchanged. As the authors explain in their methods section, it is the increased cellobiose excretion that reflects increased permeability, not the decrement in mannitol excretion. Therefore, modifications in sugar transport induced by 5-fluorouracil (5-FU) reflected only an absorptive, not a permeability, defect. The decrement in mannitol excretion parallels the decrement in d-xylose excretion, probably reflecting decreased transcellular passage of the test sugars induced by 5-FU and improved with glutamine.


Editor,—I thank Dr Craig for raising this issue but I do not see any conceptual error. The apparent inconsistency that he points out in our paper (OpenUrlCrossRefPubMedWeb of Science) is due to the controversy surrounding transcellular permeation of mannitol, as well as of other monosaccharides.1-1 While transcellular permeation of mannitol is well known, its use for osmotic shrinkage of membrane vescicles1-2 and as an extracellular fluid volume marker suggests that, at least in part, mannitol diffuses through the intercellular tight junctions. Thus it seems justified talking of permeability for mannitol. One of the reasons for its use in combination with cellobiose is the different molecular sizes of the two probes: the smaller size of mannitol allows its passage through the small tight junctions of the villi while the larger cellobiose passes through the larger tight junctions of the crypts.

Finally, we did find an increase in cellobiose excretion after fluorouracil (5-FU) that was in part prevented by oral glutamine. Although this difference did not reach statistical significance, overall the data indicate increased intestinal permeability after 5-FU, partially prevented by oral glutamine.


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