Effects of deoxycholic acid and butyrate on mucosal prostaglandin E2 release and cell proliferation in the human sigmoid colon.
BACKGROUND
A high-fat, low-fiber diet resulting in increased excretion of fecal secondary bile acids is regarded as a major risk factor for colon cancer. Incubation of human colonic biopsies with the secondary bile acid deoxycholic acid (DCA) leads to hyperproliferation with expansion of the proliferative zone, ie, a biomarker of increased cancer risk. Antiproliferative effects on various colon cancer cell lines, however, were reported for butyrate (BUT), a fermentation product of dietary fiber.


METHODS
In the following in vitro study we incubated biopsies from the normal sigmoid colon of 12 patients (age 55.8 +/- 3.6 years) with 5 microM DCA or a combination of 5 microM DCA plus 10 mM BUT (DCA/BUT) and determined epithelial proliferation by bromodeoxyuridine immunohistochemistry. As a possible mediator for the DCA effects on colonic cell proliferation, mucosal prostaglandin E2 (PGE2) release into the incubation medium was measured by 125I-PGE2 radioimmunoassay.


RESULTS
Incubation with DCA alone revealed a significantly higher labeling index for the whole crypt (.17 vs .11, p < .01) and for the upper 40% of the crypt (.05 vs .01, p < .01) compared with DCA/BUT. Mucosal PGE2 release during DCA/BUT incubation showed a trend toward lower values compared with DCA incubation (357.07 vs 434.29 pg/mg per hour; p = .07).


CONCLUSIONS
The results indicate a normalization of DCA-induced hyperproliferation of colonic epithelium by butyrate that is not clearly mediated by PGE2. Considering that nutrition affects the luminal concentrations of DCA and butyrate, our findings may have implications for colonic carcinogenesis.
Bartram
H P
HP
Department of Medicine, University of Wuerzburg, Germany.
Scheppach
W
W
Englert
S
S
Dusel
G
G
Richter
A
A
Richter
F
F
Kasper
H
H
D001973:Bromodeoxyuridine / Q000378:metabolism; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D002455:Cell Division / Q000187:drug effects*; D002756:Cholagogues and Choleretics / Q000494:pharmacology*; D003106:Colon / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D003840:Deoxycholic Acid / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism*; D004847:Epithelial Cells; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012965:Sodium Chloride / Q000494:pharmacology
D002087:Butyrates; D002756:Cholagogues and Choleretics; D003840:Deoxycholic Acid; D020148:Butyric Acid; D012965:Sodium Chloride; D001973:Bromodeoxyuridine; D015232:Dinoprostone