Butyrate and glucose metabolism by colonocytes in experimental colitis in mice

Background/aims-Impaired colonocyte metabolism of butyrate has been implica ted in the aetiopathogenesis of ulcerative colitis. Colonocyte butyrate met abolism was investigated in experimental colitis in mice. Methods-Colitis was induced in Swiss outbred white mice by oral administrat ion of 4% dextran sulphate sodium (DSS). Colonocytes isolated from colitic and normal control mice were incubated with [C-14]butyrate or glucose, and production of (CO2)-C-14, as well as of intermediate metabolites (acetoacet ate, beta-hydroxybutyrate and lactate), was measured. The effect of differe nt substrate concentrations on oxidation was also examined. Results-Butyrate oxidation (mu mol/h per mg protein; mean (SEM)) was signif icantly reduced in DSS colitis, values on day 7 of DSS administration being 0.177 (0.007) compared with 0.406 (0.035) for control animals (p<0.001). G lucose oxidation (mu mol/h per mg protein; mean (SEM)) on day 7 of DSS admi nistration was significantly higher than in controls (0.06 (0.006) v 0.027 (0.004), p<0.001). Production of beta-hydroxybutyrate was decreased and pro duction of lactate increased in DSS colitis compared with controls. Increas ing butyrate concentration from 10 to 80 mM enhanced oxidation in DSS colit is (0.036 (0.002) to 0.285 (0.040), p<0.001), although it continued to rema in lower than in controls. Surface and crypt epithelial cells showed simila r ratios of butyrate to glucose oxidation. When 1 mM DSS was added to norma l colonocytes in vitro, it did not alter butyrate oxidation. The initial hi stological lesion of DSS administration was very patchy and involved crypt cells. Abnormal butyrate oxidation became apparent only after six days of D SS administration, at which time histological abnormalities were more wides pread. Conclusions-Colonocyte metabolism of butyrate, but not of glucose, is impai red in DSS colitis, and may be important in pathophysiology. Histological a bnormalities preceded measurable defects in butyrate oxidation.