Histone modifications and the expression of genes related to epigenetic regulatory mechanisms and immune response in European sea bass (Dicentrachus labrax) fed with a diet supplemented with sodium butyrate

Abstract

Aquaculture Europe 2017 (AE2017), Cooperation for Growth, 17-20 October 2017, Dubrovnik, CroatiaThe intestinal microbiota is involved in the anaerobic fermentation of dietary otherwise indigestible carbohydrates producing short chain fatty acids (SCFAs) (Bergman, 1990). Among the SCFAs, butyrate has received particular attention due to its numerous positive effects on the health of intestinal tract and peripheral tissues (Mátis et al., 2013). The mechanisms of action of butyrate are different; many of them are related to its potent regulatory effect on gene expression since butyrate is a histone deacetylase inhibitor that play a predominant role in the epigenetic regulation of gene expression and cell function. For butyrate to exert its physiologic, cellular, and molecular effects, circulating concentrations would need to be maintained at a consistently high level. This is difficult to attain because plasma clearance of butyrate is very rapid, with a half-life of about 6 min when given intravenously in humans (Miller, 2004) A possible solution to circumvent problems associated with rapid metabolism of butyrate would be to administer it orally by giving multiple daily doses of stable derivatives of butyrate, which are being developed for use in both humans and animals. Indeed, when stable derivatives of butyrate were given orally as opposed to intravenously in humans, the half-life was increased to 40 min., and circulating butyrate concentrations reached high enough values to be efficacious. In farmed animals such as pigs and chickens, butyrate included in the diet has had a positive influence on body weight gain, feed utilization, and composition of intestinal microflora, as well as trophic effects on the intestinal epithelium through an increase in the villi length and crypt depth (Kotunia et al., 2004; Hu and Guo, 2007). Accordingly, we investigated in the European sea bass (Dicentrarchus labrax) the effects of butyrate used as a feed additive on fish epigenetics as well as its regulatory role in mucosal protection and immune homeostasis through impact on gene expression. Seven target genes related to inflammatory response and reinforcement of the epithelial defense barrier (tnfα; il1β, il-6, il-8, il-10, and muc2) and five target genes related to epigenetic modifications (dicer1, ehmt2, pcgf2, hdac11, and jarid2a) were analyzed in fish intestine and liver. We also investigated the effect of dietary butyrate supplementation on histone acetylation, by performing an immunoblotting analysis on liver core histone extractsPeer Reviewe