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.

中文翻译：

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多组学分析显示了低剂量抗生素对猪脂质代谢的影响。

为了通过表观遗传调控基因表达来研究低剂量抗生素（LDA）引起的肝细胞功能，体重增加和代谢失衡的关系，以32头断奶仔猪为动物模型，随机分为两组，每组补充0饲料或LDA（氯四环素和维吉尼亚霉素）。在实验的4周中，LDA表现出明显的促生长作用，体重的明显增加和平均日增重就是例证。使用基于液体杂交捕获的亚硫酸氢盐测序（LHC-BS）进行启动子甲基化分析，表明LDA组中的745个差异甲基化区域（DMR）中的大多数被甲基化。几种DMR显着丰富了与脂肪酸代谢途径相关的基因，例如FABP1和PCK1。此外，通过肝脏组织的链特异性转录组分析获得了71个差异表达基因（DEG），包括ALOX15，CXCL10和NNMT，这是在脂质代谢和免疫中起作用的三个关键DEG，在LDA组中表达高度升高。根据这些分子变化，通过LC-MS对血清进行的脂质组分析确定了38种显着不同的脂质，其中大多数在LDA组中被下调。我们的结果表明，LDA可以诱导关键基因的表观遗传和转录变化，并导致肝脏脂质代谢的效率提高。它们是在脂质代谢和免疫中起作用的三个关键DEG，在LDA组中的表达高度升高。根据这些分子变化，通过LC-MS对血清进行的脂质组分析发现了38种显着不同的脂质，其中大多数在LDA组中被下调。我们的结果表明，LDA可以诱导关键基因的表观遗传和转录变化，并导致肝脏脂质代谢的效率提高。它们是在脂质代谢和免疫中起作用的三个关键DEG，在LDA组中的表达高度升高。根据这些分子变化，通过LC-MS对血清进行的脂质组分析发现了38种显着不同的脂质，其中大多数在LDA组中被下调。我们的结果表明，LDA可以诱导关键基因的表观遗传和转录变化，并导致肝脏脂质代谢的效率提高。