Multi-omics profiling highlights lipid metabolism alterations of pigs fed with low-dose antibiotics

Based on the gut-liver axis theory, to survey the effect of low-dose antibiotic (LDA) to hepatocellular functions of weight gain and metabolic imbalance by epigenetic transcription regulation, 32 weaned piglets were employed as the animal models and half were treated with Chlorotetracycline and Virginiamycin for four weeks. During the experiment, LDA showed an obviously growth-promoting effect, which was exemplified by the significantly elevated body weight and average daily gain. The DNA methylome profiling of promoter using liquid hybridization capture-based bisulfite sequencing (LHC-BS) indicated most of 745 differential methylation regions (DMRs) were hypermethylated in the LDA group, and some other DMRs were significantly enriched in genes related with fatty acids metabolic pathways, such as FABP1 and PCK1. Meanwhile, three key DEGs with the function of lipid metabolism and immunity were obtained by the liver strand-specific transcriptome analysis, including ALOX15, CXCL10 and NNMT, which were highly elevated for expressions in the LDA group. Correspondingly, the lipidome analyses of serum by LC-MS identified 38 significantly differential lipids, most of which were down-regulated in the LDA group. All these results suggest antibiotics could induce epigenetic and transcriptional changes of key genes related lipid metabolism pathway, and contributed to a more efficient metabolism of lipids. 32 samples for ssRNA-seq,8 samples for LHC-BS