Exposure Of Mice To Antibiotics Perturbs Their Hepatic Energy Metabolism And Gut Microbiome

Since 1950 s,antibiotics have made a great contribution to public health as antibacterial agent with broad-spectrum,high-potency.Because of the campaigns are limited,the abuse of antibiotics become more and more serious.Recently,antibiotics are detected from rivers or soils,and those antibiotics may certain unknown threats to human health.Penicllin G(Pen G)and Erythromycin(Ery)are widely used in medicine and husbandry areas.The aim of our study is to evaluate the effect of oral exposure to Pen G,Ery and their mixture on the lipid metabolism,inflammation and intestinal flora of in mice.Firstly,mice were randomly divided into 8 groups,9 mice in each group.Then 8 groups were divided into two experiments: Experiment 1: four groups of mice were orally administered 60 ?g/ml Pen G,Ery and Mix(half dose of each)for 6 weeks supplied in drinking water;Experiment 2: the other four groups of mice were orally administered 10 ?g/ml Pen G,Ery and Mix(half dose of each)for 14 weeks supplied in drinking water.After exposure,the mice were sacrificed.Liver,fat,ileum,colon and cecum contents were quickly removed and stored at-80℃ for further use.Secondly,to study the effect of antibiotics on the lipid metabolism in mice,four-week-old male C57BL/6J mice were randomly divided into five groups and treated with indicated antibiotics for 90 days with high fat chow.After 90 days,all of the mice were sacrificed.Liver and fat were quickly removed and stored at-80℃.The results showed that Ery(60 ?g/ml)exposure for 6 weeks significantly increased the body weights of mice.The relative liver weights increased after antibiotics treatment.The oil red O staining showed that,no matter control chow or high fat chow,the lipid accumulations were observed in all antibiotics treated groups.Moreover,the transcription levels of the main genes related to FFA synthesis,transport and TG synthesis including srebp-1c,acc,fat,gpat significantly increased when treated with high-dose of antibiotics.In addition,low-dose of antibiotics treatment significantly increased the transcription levels of genes related to FFA synthesis;the transcription levels of ppar-? also increased in the liver of mice which treated with antibiotics and fed with high fat chow.It demonstrated that antibiotics,no matter short-term treatment or long-term treatment,could perturb the lipid metabolism and resulted in the increase of liver lipid accumulation.The 16 s rDNA sequencing of cecum contents showed that the intestinal flora was significantly changed by antibiotics treatment,especially in the Ery and Mix treated groups.Ery and Mix treatment groups decreased the relative abundance of Bacteroidaceae and Porphyromonadaceae while increased the relative abundance of Lachnospiraceae and Ruminococcaceae.Firmicutes and Bacteroidetes in fecal were changed quickly during the antibiotics exposure,and the relative abundance of Bacteroidetes decreased significantly.In addition,the antibiotics exposure also significantly increased serum LPS levels,and the transcription of genes related to inflammation signaling pathways and proinflammatory factors,such as tlr4,nf-?b.All the results demonstrated that antibiotics changed intestinal flora and inhibited ileum immune,which may result in low level inflammation in mice.In conclusion,oral exposure to Pen G,Ery and therir mixtures disturbed the hepatic lipid metabolism,regulated intestinal flora,inhibited ileum immune in male mice.The present study provided some specific evidence to the relationship between antibiotics and human health.