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

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.