Short-chain fatty acids (SCFAs) are mainly produced by microbiota through the fermentation of carbohydrates in the intestine. Acetate, propionate, and butyrate are the most abundant SCFA metabolites and have been shown to be important in the maintenance of host health. In this study, head kidney macrophages (HKMs) were isolated and cultured from turbots. We found that the antibacterial activity of HKMs was increased after these cells were incubated with sodium butyrate, sodium propionate or sodium acetate. Interestingly, our results showed that all three SCFAs enhanced the expression of hypoxia inducible factor-1 α (HIF-1α) in HKMs, and further study confirmed that butyrate augmented the oxygen consumption of these cells. Moreover, HIF-1α inhibition diminished the butyrate-promoted intracellular bacterial killing activity of macrophages, and SCFAs also raised the gene expression and activity of lysozymes in HKMs via HIF-1α signaling. In addition, our results suggested that butyrate induced HIF-1α expression and the bactericidal activity of HKMs through histone deacetylase inhibition, while G protein-coupled receptors did not contribute to this effect. Finally, we demonstrated that butyrate induced a similar response in the murine macrophage cell line RAW264.7. In conclusion, our results demonstrated that SCFAs promoted HIF-1α expression via histone deacetylase inhibition, leading to the enhanced production of antibacterial effectors and increased bacterial killing of macrophages.

Short-chain fatty acids (SCFAs) are the products of the microbial fermentation of dietary fiber in the intestine. Acetate, propionate, and butyrate are the most abundant SCFA metabolites and play an important role in maintaining host health. This study was aimed at investigating the effects of sodium propionate (NaP) supplementation in the diet with a high proportion of soybean meal (SBM) on the growth, inflammatory status, and anti-infectious ability in juvenile turbot. Four experimental diets were designed: (1) fish meal- (FM-) based diet (control group), (2) SBM protein replacing 45% FM protein in the diet (high SBM group), (3) 0.5% NaP supplementation in the high SBM diet (high SBM+0.5% NaP group), and (4) 1.0% NaP supplementation in the high SBM diet (high SBM+1.0% NaP group). The results confirmed that the fish fed the high SBM diet for 8 weeks showed the decreased growth performance, the typical enteritis symptoms, and the increased mortality responding to Edwardsiella tarda (E. tarda) infection. However, 0.5% NaP supplementation in the high SBM diet promoted the growth performance of turbot and restored the activities of digestive enzymes in the intestine. Moreover, dietary NaP ameliorated the intestinal morphology, enhanced the expression of intestinal tight junction proteins, improved the antioxidant capacity, and suppressed the inflammatory status in turbot. Finally, the expression of antibacterial components and the resistance to bacterial infection were increased in NaP-fed turbot, especially in high SBM+1.0% NaP group. In conclusion, the supplementation of NaP in high SBM diet promotes the growth and health in turbot and provides a theoretical basis for the development of NaP as a functional additive in fish feed.