Noninvasive evaluation of intestinal lactase with 4-Galactosylxylose: Comparison with 3- and 2-Galactosylxylose and optimization of the method in rats

Abstract

[Background]: Urinary excretion of D-xylose by suckling rats after ingestion of a mixture of 4-, 3-, and 2-galactosylxyloses reflects lactase activity in vivo. We aimed to select the most convenient of these disaccharides for detecting changes of the enzyme activity in vivo and to optimize the method. [Methods]: 4-, 3-, and 2-Galactosylxyloses were synthesized and purified, then orally administered to suckling rats of different ages. D-Xylose was measured colorimetrically by the phloroglucinol reaction in urine and plasma. Lactase activity was determined in extracts of small intestine mucosa with lactose, galactosylxyloses, and phlorizin as substrates. [Results]: D-Xylose appeared in the urine in a dose-dependent manner after ingestion of any of the 3 galactosylxylose disaccharides. Correlation between D-xylose elimination and intestinal lactase activity was highest with 4-galactosylxylose (r = 0.97; n = 24), lower with 2-galactosylxylose (r = 0.89; n = 24), and lowest with 3-galactosylxylose (r = 0.34; n = 23). The kinetic properties of intestinal lactase accounted for these differences. D-Xylose concentration in plasma after administration of 4-galactosylxylose also correlated with lactase activity (r = 0.93; n = 33). [Conclusions]: 4-Galactosylxylose is the most suitable compound for the evaluation of lactase activity in vivo. Measurement of the derived D-xylose in either urine or blood gives an estimate of the total lactose digestive capacity of the small intestine. The optimized method holds promise for development of a simple, low-cost, and reliable new test for the noninvasive diagnosis of hypolactasia.