Two biological activities of butyrate in the
colon (suppression of proliferation of colonic epithelial stem cells and
inflammation) correlate with inhibition of histone deacetylases. Cellular and biochemical studies of molecules
similar in structure to butyrate, but different in molecular details (functional
groups, chain-length, deuteration, oxidation level, fluorination, or degree of unsaturation)
demonstrated that these activities were sensitive to molecular structure, and were
compatible with the hypothesis that butyrate acts by binding to the Zn<sup>2+</sup>
in the catalytic site of histone deacetylases. Structure-activity
relationships drawn from a set of 36 compounds offer a starting point for the design
of new compounds targeting the inhibition of histone deacetylases. The observation that butyrate was more potent
than other short-chain fatty acids is compatible with the hypothesis that
crypts evolved (at least in part), to separate stem cells at the base of crypts
from butyrate produced by commensal bacteria.
Establishment of a Novel Lingual Organoid Culture System: Generation of Organoids Having Mature Keratinized Epithelium from Adult Epithelial Stem Cells