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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
Author(s) -
Sengupta Shomik,
Tang ChoongLeong,
Wong Cynthia S. M.,
Tjandra Joe J.,
Gibson Peter R.
Publication year - 2002
Publication title -
anz journal of surgery
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.426
H-Index - 70
eISSN - 1445-2197
pISSN - 1445-1433
DOI - 10.1046/j.1445-2197.2002.t01-1-02586.x
Subject(s) - butyrate , crypt , medicine , mitotic index , endocrinology , lumen (anatomy) , gastroenterology , epithelium , pathology , biochemistry , biology , mitosis , fermentation , microbiology and biotechnology
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.