Diet Containing Whey Protein, Glutamine, and TGFβ Modulates Gut Protein Metabolism During Chemotherapy-Induced Mucositis in Rats

Background Mucositis, a common side effect of chemotherapy, is characterized by compromised digestive function, barrier integrity and immune competence. Aims Our aim was to evaluate the impact of a specifically designed diet Clinutren Protect® (CP), which contains whey proteins, TGFβ-rich casein, and free glutamine, on mucositis in rats. Methods Mucositis was induced by three consecutive injections (day 0, day 1, day 2) of methotrexate (2.5 mg/kg). Rats had free access to CP or placebo diets from days −7 to 9. In the placebo diet, whey proteins and TGFβ-rich casein were replaced by TGFβ-free casein and glutamine by alanine. Intestinal parameters were assessed at day 3 and 9. Values, expressed as mean ± SEM, were compared using two-way ANOVA. Results At day 3, villus height was markedly decreased in the placebo (296 ± 11 μm) and CP groups (360 ± 10 μm) compared with controls (464 ± 27 μm), but more markedly in the placebo as compared to CP group. The intestinal damage score was also reduced in the CP compared with the placebo group. Glutathione content increased in the CP compared with the placebo group (2.2 ± 0.2 vs. 1.7 ± 0.2 μmol/g tissue). Gut protein metabolism was more affected in the placebo than in the CP group. The fractional synthesis rate was decreased in the placebo group (93.8 ± 4.9%/day) compared with controls (121.5 ± 12.1, P < 0.05), but not in the CP group (106.0 ± 13.1). In addition, at day 9, rats exhibited improved body weight and food intake recovery in the CP compared to the placebo group. Conclusions Clinutren Protect® feeding reduces intestinal injury in the acute phase of methotrexate-induced mucositis in rats and improves recovery.