Epigenetic orchestrator and drug enhancer: dual roles of butyrate in regulating post-translational modification and optimizing therapeutic delivery

Butyrate, a four-carbon short-chain fatty acid produced by gut microbiota, has been widely recognized for its diverse physiological benefits. Functioning as a natural HDAC inhibitor, it critically modulates various protein post-translational modifications (PTMs). The endogenous transport systems mediating butyrate absorption provide a promising platform for developing butyrate-modified drugs with enhanced bioavailability and tissue targeting. Here, we offer a concise overview of butyrate’s production, transport, and metabolism, focusing on its role in regulating PTMs and the potential therapeutic applications of butyrate transporters in drug delivery. Building on current butyrate modification strategies, we also review its applications in drug formulation enhancement and synergistic therapeutic combinations. In summary, butyrate can function as a natural modulator of specific PTMs and as a drug modifier enhancing therapeutic delivery.