The effects of short-chain fatty acids on colon epithelial proliferation and survival depend on the cellular phenotype.
OBJECTIVE
The short-chain fatty acids (SCFA) are produced via anaerobic bacterial fermentation of dietary fiber within the colonic lumen. Among them, butyrate is thought to protect against colon carcinogenesis. However, few studies analyze the effects of butyrate, and other SCFA, on normal epithelial cells and on epithelial regeneration during disease recovery. Since there are controversial in vitro studies, we have explored the effects of SCFA on different biological processes.


METHODS
We used both tumoral (HT-29) and normal (FHC) epithelial cells at different phenotypic states. In addition, we analyzed the in vivo activity of soluble dietary fiber and SCFA production in the proliferation rate and regeneration of intestinal epithelial cells.


RESULTS
The effect of butyrate on epithelial cells depends on the phenotypic cellular state. Thus, in nondifferentiated, high proliferative adenocarcinoma cells, butyrate significantly inhibited proliferation while increased differentiation and apoptosis, whereas other SCFA studied did not. However, in normal cells or in differentiated cultures as well as in in vivo studies, the normal proliferation and regeneration of damaged epithelium is not affected by butyrate or SCFA exposure.


CONCLUSIONS
Although butyrate could exert antiproliferative effects in tumor progression, its production is safe and without consequences for the normal epithelium growth.
Comalada
Mònica
M
Department of Pharmacology, School of Pharmacy, University of Granada, Campus Universitario "La Cartuja" s/n, 18071, Granada, Spain. jxaus@puleva.es
Bailón
Elvira
E
de Haro
Oscar
O
Lara-Villoslada
Federico
F
Xaus
Jordi
J
Zarzuelo
Antonio
A
Gálvez
Julio
J
D000230:Adenocarcinoma / Q000473:pathology / Q000517:prevention & control*; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D020148:Butyric Acid / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology / Q000517:prevention & control*; D004847:Epithelial Cells / Q000187:drug effects* / Q000201:enzymology; D005232:Fatty Acids, Volatile / Q000494:pharmacology; D005260:Female; D019073:HT29 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D010641:Phenotype; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar
D005232:Fatty Acids, Volatile; D018809:Proliferating Cell Nuclear Antigen; D020148:Butyric Acid; D000469:Alkaline Phosphatase