Microbial short chain fatty acids: Effective histone deacetylase inhibitors in immune regulation (Review)

Histone acetylation modification represents a common epigenetic regulatory mechanism, carrying out an indispensable role in cellular gene transcription and function. Histone deacetylases (HDACs) are responsible for regulating gene expression by controlling the deacetylation of histones and non‑histone proteins, and can serve as effective targets for participating in immune regulation. Short‑chain fatty acids (SCFAs) are important metabolites produced by the gut microbiota that modulate host immunity. SCFAs possess extensive inhibitory activities on class I and II HDACs, as well as acetylation‑modifying effects. Based on these, the present review initially introduces the microbial synthesis and intestinal absorption of SCFAs, as well as the classification and function of HDACs. Subsequently, the present review comprehensively summarizes the direct regulatory effects of SCFAs on immune cells through HDAC inhibition, encompassing innate immune cells (macrophages, dendritic cells, neutrophils, mast cells and natural killer cells) as well as T/B lymphocytes. Moreover, the present review further discusses the local intestinal and extra‑intestinal (primarily involving the liver, kidney, nerves and blood vessels) protective effects of SCFAs, which are mediated by their HDAC‑inhibiting activities. Finally, the present review summarizes the therapeutic potential of SCFAs as effective HDAC inhibitors in ameliorating intestinal and extra‑intestinal diseases and discusses the research prospects. The present review aims to elucidate the regulatory effects of SCFAs on host immunity through HDAC inhibition, highlighting their therapeutic potential for human diseases.