The polyamines spermidine and spermine (SPM) and their precursor putrescine are ubiquitous polycationic compounds found in all mammalian cells. [1][2][3][4][5] These compounds are essential for the maintenance of cell growth in many tissues, and intracellular levels of polyamines are maintained within narrow limits.The polyamines are present in variable amounts in almost all food or foodstuffs. In humans, a typical diet might contribute hundreds of micromoles of polyamines per day to the gut lumen, 6,7) and ingested food may be the major source of polyamines in the lumen of the upper small bowel. Exogenous polyamines play a role in the maintenance of normal growth and function of the intestinal tract. 8,9) Oral administration of SPM induces precocious maturation of the intestine. [10][11][12][13][14][15] Oral polyamines have also been shown to have beneficial effects on healing 16,17) and prevention [18][19][20] of gastrointestinal damage.The gastrointestinal tract acts as a barrier against the invasion of exogenous proteins into the body. This barrier function is due to enzymes that degrade the proteins and also due to impermeability of the proteins to the membrane due to their large molecular weight. Because most food-originated proteins are digested in the gastrointestinal tract before absorption, naturally occurring protein uptake from the intestinal epithelium should be low. In reality, however, the barrier function of the small intestinal epithelium in mammals is incomplete and, to a limited extent, macromolecules can pass from the lumen into the circulation. 21,22) In an in situ loop study and in an in vivo oral absorption study, we showed that polyamines, especially SPM, can enhance the intestinal absorption of fluorescein isothiocyanatelabeled dextran (molecular weight (MW) 4400, FD-4), a hydrophilic model macromolecule, without causing any significant damage in the intestinal tract in rats.23) We also suggested that the absorption-enhancing mechanism of SPM partly includes opening the tight junctions of the epithelium via the paracellular route by measuring FD-4 permeation and transepithelial electrical resistance in the human intestinal Caco-2 cell line. We have speculated that excess absorption of macromolecules by the action of SPM, one of the compounds in food, has widespread health effects. Thus, modulation of the gastrointestinal epithelial barrier by ingested luminal polyamines may influence the induction of food allergies. Gastrointestinal permeability enhanced by daily ingestion of polyamines plays a part in the regulation of the induction of tolerance because oral tolerance induction is related to the gradual and continuous absorption of a food allergen. 24,25) In contrast, after sensitization to an antigen, an increase in gastrointestinal permeability by polyamines may facilitate the absorption of the allergen into the circulation and lead to an anaphylactic response as an immediate hypersensitivity reaction to the antigen.The aim of this study was to determine whether an SPMinduced increase...