DIFFERENTIAL IN-VIVO AND IN-VITRO INTESTINAL PERMEABILITY TO LACTULOSE AND MANNITOL IN ANIMALS AND HUMANS - A HYPOTHESIS

Background/Aims: Clinical interpretation of urinary recovery ratios of lactulose and mannitol is hampered by incomplete understanding of the mechanisms of transmucosal passage. The aim of this study was to comp are in vivo and in vitro probe permeability. Methods: Stripped sheets of small intestine from rodents and human biopsy specimens were mounte d in Ussing chambers, and mucosa-to-serosa fluxes of lactulose and man nitol were determined. Urinary recovery of orally applied probes was m easured in rodents, cats, and humans. Results: In vitro lactulose/mann itol flux ratios were close to 0.8 in all species. Urinary recovery ra tios differed between rodents and cats or humans; low ratios in cats a nd humans were due to high mannitol recovery. Conclusions: Interspecie s variation in urinary recovery of mannitol is caused by differences s pecific for the intact small intestines in vivo. Because hyperosmolali ty of villus tips in vivo varies, being highest in humans and cats as a result of vascular countercurrent multiplication, it is hypothesized that the high urinary recovery of mannitol in these species is caused by solvent drag through pores that allow the passage of mannitol but not of lactulose. Therefore, the lactulose/mannitol ratio is primarily a standard for the normal functioning of villus epithelial cells in m etabolite absorption and for normal villus blood flow.