Caprylic acid and nonanoic acid upregulate endogenous host defense peptides to enhance intestinal epithelial immunological barrier function via histone deacetylase inhibition

The intestinal epithelial barrier plays a critical role in the etiopathogenesis of ulcerative colitis. This study aims to explore the potential effects and underlying mechanisms of medium chain fatty acids (caprylic acid and nonanoic acid) on intestinal epithelial barrier function. Using the porcine jejunal epithelial cell line IPEC-J2, a well -established model, challenged with Escherichia coil ATCC 43889 (O157:H7), we found that treatment with caprylic acid (C8) and nonanoic acid (C9) significantly reduced bacterial translocation, enhanced antibacterial activity, and remarkably increased the secretion of porcine beta-defensins 1 (pBD-1) and pBD-2. Mechanistically, like TSA (a histone deacetylase inhibitor), C8 and C9 attenuated the activity of the classical histone deacetylase pathway to facilitate the acetylation of histone 3 lysine 9 (H3K9) at the promoters pBD-1 and pBD-2, and consequently augmented the gene expression of pBD-1 and pBD-2. In conclusion, with their combined antibacterial and defense peptide-induced roles, the use of C8 and C9 may provide a novel method to protect the intestinal barrier of animals and humans from bacterial infection.