BACKGROUND: Luminal butyrate may be trophic to the colonic epithelium, but this effect is poorly characterized. The aim of the present study was to define the dose-response, time-course, site-specificity and the dependence on background diet of the effects of butyrate on epithelial proliferation in normal distal colon, using an in vivo rat model of colonic substrate delivery. METHODS: Male Sprague-Dawley rats, maintained on a fibre-free diet, had butyrate infused twice daily into the colonic lumen via polyethylene tubes placed at laparotomy. Varying dose levels (0-80 micro mol/d; 4 d), site (caecal vs distal colonic), duration of infusions (1-5 weeks; 80 micro mol/d), or dietary fibre intake were investigated. Epithelial proliferative indices were assessed stathmokinetically. RESULTS: Four-day infusions of butyrate led to a progressive trophic effect (cells/crypt column increased from 37.9 +/- 1.6 at 0 micro mol/d to 44.7 +/- 1.2 at 80 micro mol/d) on fibre-deprived colonic mucosa, related linearly to the daily butyrate dose (P < 0.001, linear regression). This effect was mediated by increases in the number and proportion of mitoses, related to the square of the butyrate dose (P < 0.001 in each case, polynomial regression). Butyrate (80 micro mol/d) was associated with significantly higher cellularity (59.9 +/- 1.4) and mitotic activity (4.9 +/- 0.6) per crypt column compared to vehicle controls (50.3 +/- 1.6 and 0.9 +/- 0.2, respectively; P < 0.05, t-tests), at 1 and 3 weeks, but not at 5 weeks. Butyrate had similar effects on distal colonic crypt cellularity (62.0 +/- 1.5) when delivered caecally, but in rats fed a fibre-containing diet, colonic crypt cellularity (55.3 +/- 3.2) was similar to baseline (59.6 +/- 1.9). CONCLUSIONS: Trophic effects of butyrate are concentration-dependent and occur at low doses in the short term, but are not sustained over longer periods. They are seen only in a fibre-deprived state and appear to be independent of the site of administration.
BACKGROUND: Luminal butyrate may be trophic to the colonic epithelium, but this effect is poorly characterized. The aim of the present study was to define the dose-response, time-course, site-specificity and the dependence on background diet of the effects of butyrate on epithelial proliferation in normal distal colon, using an in vivo rat model of colonic substrate delivery. METHODS: Male Sprague-Dawley rats, maintained on a fibre-free diet, had butyrate infused twice daily into the colonic lumen via polyethylene tubes placed at laparotomy. Varying dose levels (0-80 micro mol/d; 4 d), site (caecal vs distal colonic), duration of infusions (1-5 weeks; 80 micro mol/d), or dietary fibre intake were investigated. Epithelial proliferative indices were assessed stathmokinetically. RESULTS: Four-day infusions of butyrate led to a progressive trophic effect (cells/crypt column increased from 37.9 +/- 1.6 at 0 micro mol/d to 44.7 +/- 1.2 at 80 micro mol/d) on fibre-deprived colonic mucosa, related linearly to the daily butyrate dose (P < 0.001, linear regression). This effect was mediated by increases in the number and proportion of mitoses, related to the square of the butyrate dose (P < 0.001 in each case, polynomial regression). Butyrate (80 micro mol/d) was associated with significantly higher cellularity (59.9 +/- 1.4) and mitotic activity (4.9 +/- 0.6) per crypt column compared to vehicle controls (50.3 +/- 1.6 and 0.9 +/- 0.2, respectively; P < 0.05, t-tests), at 1 and 3 weeks, but not at 5 weeks. Butyrate had similar effects on distal colonic crypt cellularity (62.0 +/- 1.5) when delivered caecally, but in rats fed a fibre-containing diet, colonic crypt cellularity (55.3 +/- 3.2) was similar to baseline (59.6 +/- 1.9). CONCLUSIONS: Trophic effects of butyrate are concentration-dependent and occur at low doses in the short term, but are not sustained over longer periods. They are seen only in a fibre-deprived state and appear to be independent of the site of administration.
Authors: Ariano Jose Freitas de Oliveira; Francisco Edilson Leite Pinto Júnior; Maria Célia Carvalho Formiga; Syomara Pereira da Costa Melo; Jose Brandao-Neto; Ana Maria de Oliveira Ramos Journal: Clinics (Sao Paulo) Date: 2010 Impact factor: 2.365