IngentaConnect Colonic epithelial atrophy induced by a fibre-free diet in rats i...

Abstract:

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 µmol/d; 4 d), site (caecal vs distal colonic), duration of infusions (1−5 weeks; 80 µmol/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 µmol/d to 44.7 ± 1.2 at 80 µmol/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 µmol/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.

Keywords: animal disease models; butyrates; cell division; colon; dietary fibre; epithelium; fatty acids; infusions; sprague dawley rats

Document Type: Research article

DOI: 10.1046/j.1445-2197.2002.t01-1-02586.x

Affiliations: 1: Surgery and 2: Medicine, The Royal Melbourne Hospital, Victoria, Australia

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Colonic epithelial atrophy induced by a fibre-free diet in rats is reversed by minimal amounts of luminal butyrate, but only in the short term