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Butyrate (butyric acid) is a four-carbon
short-chain fatty acid produced primarily by intestinal microbial
fermentation of dietary fibre and resistant starch. It is a major energy
source for normal colonocytes and also functions as a signalling metabolite
through inhibition of histone deacetylases (HDACs) and
activation of receptors including GPR109A/HCAR2 and
FFAR2/GPR43. In colorectal cancer cells,
butyrate ↑ commonly causes intracellular accumulation,
HDAC inhibition, cell-cycle arrest, differentiation, and apoptosis while
reducing proliferation and inflammatory signalling. This contrasting effect
in normal versus malignant colonocytes is sometimes called the
butyrate paradox: normal colonocytes efficiently oxidize
butyrate as fuel, whereas glycolytic cancer cells may metabolize less
butyrate, permitting greater nuclear accumulation and HDAC inhibition.
Butyrate is an individual metabolite and microbial postbiotic, separate from the
broader short-chain fatty acid group and from acetate and propionate.
Effects outside the colon are dose-, tissue-, microbiome-, and
metabolism-dependent, and most direct anticancer evidence remains
preclinical.
Colorectal cancer reference;
Intestinal biology review;
HDAC inhibition reference.
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