Multi-omics profiling highlights lipid metabolism alterations in pigs fed low-dose antibiotics.

In order to study the relations of hepatocellular functions, weight gain and metabolic imbalance caused by low-dose antibiotics (LDA) via epigenetic regulation of gene transcription, 32 weaned piglets were employed as animal models and randomly allocated into two groups with diets supplemented with 0 or LDA (chlorotetracycline and virginiamycin). During the 4 weeks of the experiment, LDA showed a clear growth-promoting effect, which was exemplified by the significantly elevated body weight and average daily gain. Promoter methylome profiling using liquid hybridization capture-based bisulfite sequencing (LHC-BS) indicated that most of the 745 differential methylation regions (DMRs) were hypermethylated in the LDA group. Several DMRs were significantly enriched in genes related with fatty acids metabolic pathways, such as FABP1 and PCK1. In addition, 71 differentially expressed genes (DEGs) were obtained by strand-specific transcriptome analysis of liver tissues, including ALOX15, CXCL10 and NNMT, which are three key DEGs that function in lipid metabolism and immunity and which had highly elevated expression in the LDA group. In accordance with these molecular changes, the lipidome analyses of serum by LC-MS identified 38 significantly differential lipids, most of which were downregulated in the LDA group. Our results indicate that LDA could induce epigenetic and transcriptional changes of key genes and lead to enhanced efficiency of lipid metabolism in the liver.