Continuous enteral administration can overcome the limited capacity to absorb glucose in rats with methotrexate-induced gastrointestinal mucositis

Background: Patients with chemotherapy-induced gastrointestinal mucositis often suffer from weight loss. It is not well known how to enterally feed mucositis patients, potentially experiencing malabsorption. Recently, we showed in a rat model of methotrexate (MTX)-induced mucositis that intestinal absorption of glucose in trace amounts is still intact. We now determined the quantitative capacity to absorb glucose in rats with mucositis, relative to controls. Methods: We administered a physiologically relevant amount of [1- ¹³C]glucose-enriched glucose (meal size) as a bolus by oral gavage (2 g/kg once) or continuously by intraduodenal infusion (±1.9 g/(kg·h) for 5 h) to rats with MTX-induced mucositis and controls. Blood [1-¹³C]glucose concentrations were determined during the experimental period. To calculate the quantitative absorptive capacity, Steele's one-compartment model, including simultaneous intravenous infusion of [6,6- ²H₂]glucose, was used. After the experiment, jejunal histology and plasma citrulline concentrations were assessed. Results: MTX-induced mucositis was confirmed by a reduction in villus length and plasma citrulline (both -57 %, relative to controls, P < 0.01). When glucose was administered as a bolus, MTX-treated rats only absorbed 15 % of administered glucose, compared with 85 % in controls (medians, P < 0.01). Upon continuous intraduodenal glucose infusion, the median absorptive capacity for glucose in MTX-treated rats did not differ from controls (80 versus 93 % of administered glucose respectively, P = 0.06). However, glucose absorption differed substantially between individual MTX-treated rats (range, 21-95 %), which correlated poorly with villus length (rho = 0.54, P = 0.030) and plasma citrulline (rho = 0.56, P = 0.024). Conclusion: Continuous enteral administration can almost completely overcome the reduced absorptive capacity for glucose in rats with mucositis.