Overview
Acetate (acetic acid, C2) is the most abundant SCFA in the colon (~60% of total SCFAs) and the primary cross-feeding substrate for butyrate production. Produced by Bacteroides, Bifidobacterium, Prevotella, and acetogens from dietary fiber fermentation, acetate reaches portal concentrations of 100–300 µM and peripheral circulation at 50–200 µM — making it the only SCFA with significant systemic concentrations.
Functions
- cross feeding substrate: Acetate is converted to butyrate by butyrate-producing Firmicutes (roseburia, faecalibacterium prausnitzii) via butyryl-CoA:acetate CoA-transferase. This acetate→butyrate chain means acetate producers are upstream of the entire butyrate-dependent protective cascade [1].
- Appetite regulation: Acetate crosses the blood-brain barrier and reduces appetite via hypothalamic signaling.
- Immune modulation: Activates GPR43 (FFAR2) on immune cells, promoting neutrophil recruitment and Treg differentiation.
- Histone acetylation: Systemic acetate contributes to histone H3/H4 acetylation in peripheral tissues — an epigenetic mechanism linking gut microbiome to systemic gene regulation.
- Cancer: Context-dependent effects — anti-proliferative via HDAC inhibition in some cancers, but Acetyl-CoA supply for lipogenesis in others [2].
Cross-References
- short chain fatty acids — SCFA umbrella
- butyrate — downstream product of acetate cross-feeding
- cross feeding — acetate→butyrate trophic chain
- bacteroides — major acetate producer
- bifidobacterium — major acetate producer
- dietary fiber — fermentation substrate