title: Understanding measurements of intestinal permeability in healthy humans with urine lactulose and mannitol excretion.
abstract: Our aim was to understand the information from differential two-sugar excretion (2-SE) in measuring intestinal permeability. In a crossover study in 12 healthy volunteers, we compared urinary excretion ratios of lactulose (L) to mannitol [(M) LMR] after ingestion in liquid formulation (LF) or in delayed-release, methacrylate-coated capsules (CAP). Both formulations were radiolabelled. Urine was collected every 2 h from 0 to 8 h, and from 8 to 24 h. Two hours after LF, gastric residual was 15.9 +/- 6.2% (SEM), and the percentage in colon was 49.6 +/- 7.8%; in 11/12 participants, liquid had entered colon within 2 h. Average CAP arrival time in colon was 5.16 +/- 0.46 h (mode 6 h). After LF, mannitol was extensively absorbed in the first 8 h; lactulose absorption was low throughout the 24 h. After the LF, the LMR (geometric mean, 95% CI per h) in the 0-2 h urine was [0.08 (0.05, 0.11)], which was lower than in 8-24 h urine [0.32 (0.16, 0.46); P < 0.05]. Urine LMRs at 8-24 h were similar after LF or CAP. We concluded that, after LF, sugar excretion in 0-2 h urine may reflect both SI and colon permeability. Colonic permeability is reflected by urine sugar excretion between 6 and 24 h. CAP delivery reduces mannitol excreted at 0-6 h, compared with LF. The 0-5 or 6 h 2-SE urine likely reflects both SI and colon permeability; the higher LMR in the 8-24 h urine relative to 0-2 h urine should be interpreted with caution and does not mean that colon is more permeable than SI.
authors.affiliation: Clinical Enteric Neuroscience Translational and Epidemiological Research Group, Mayo Clinic, Rochester, MN 55905, USA. camilleri.michael@mayo.edu
authors.forename: M
authors.initials: M
authors.lastname: Camilleri
authors.forename: A
authors.initials: A
authors.lastname: Nadeau
authors.forename: J
authors.initials: J
authors.lastname: Lamsam
authors.forename: S Linker
authors.initials: SL
authors.lastname: Nord
authors.forename: M
authors.initials: M
authors.lastname: Ryks
authors.forename: D
authors.initials: D
authors.lastname: Burton
authors.forename: S
authors.initials: S
authors.lastname: Sweetser
authors.forename: A R
authors.initials: AR
authors.lastname: Zinsmeister
authors.forename: R
authors.initials: R
authors.lastname: Singh
mesh_terms: D000284:Administration, Oral; D002853:Chromatography, Liquid / Q000379:methods; D018592:Cross-Over Studies; D005260:Female; D005746:Gastric Emptying; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007792:Lactulose / Q000008:administration & dosage / Q000652:urine*; D008297:Male; D008353:Mannitol / Q000008:administration & dosage / Q000652:urine*; D013058:Mass Spectrometry / Q000379:methods; D010539:Permeability; D015203:Reproducibility of Results
chemical_list: D008353:Mannitol; D007792:Lactulose