| Antibiotics have been widely used for disease prevention and treatment of human and animals. Meanwhile, the use of antibiotics as growth promoter in animal husbandry improves the utilization rate of feed and promotes animal growth. Antibiotics can disturb the intestinal microbial community, which plays a fundamental role in animals’growth and health. In spite of the clear benefits of antibiotics to agriculture, antibiotics use in combination with increase and spread of antibiotic resistance has posed huge threats upon human health and ecological safety. This thesis aimed to explore the effects of tetracycline hydrochloride (TET) exposure on mice metabolism and intestinal microbial structure and function and to assess the potential metabolic toxicities induced by the TET exposure.Some lesions were observed in the liver tissue of the mice exposed to TET, which presented an obvious dose-effect relationship. Liver tissue lesions were difficult to recover completely in the high-dose TET group.1H nuclear magnetic resonance spectroscopy (’H-NMR) assays and partial least squares discriminant analysis (PLS-DA) showed that mice metabolism was disturbed by TET exposure. Many of the altered metabolic substances in the serum and urine were involved in the protein metabolism, energy metabolism and lipid metabolism in mice, indicating that the groups of TET and the control groups had significant differences. After two-week recovery without TET treatment, the effects of mice metabolism in the low-dose TET groups could been restored, but the effects were difficult to recover completely in the high-dose TET groups.Illumina sequencing, bioinformatics technology, PCR and qPCR were used to characterize the shifts of mice intestinal microbial antibiotic resistance patterns after TET exposure at different doses and recovery. The results showed that the mice gut microbiome harbors diverse resistance genes even in the absence of TET selective pressure. In the mice intestinal microbiota, antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs) increased in abundance and diversity in the 10 g/L TET group. After two-week recovery, in the 10 g/L TET group, the abundance and diversity of ARGs were reduced slightly, but remained high. But the abundance and diversity of MGEs were decreased significantly. TET exposure could improve the intestinal microbial antibiotic resistance, whichi might pose threat to human health and ecological safety.We used 454 pyrosequencing, Illumina sequencing and bioinformatics technology to explore the shifts of mice intestinal microbial community structure and functions under stress of different doses of TET. After two-week exposure, TET disturbed the intestinal microbial community. The abundance of Firmicutes phylum was increased and the abundance of Bacteroidetes was decreased in the 0.5 g/L TET group after two-week exposure. And the abundances of clusters of orthologous groups (COGs) of proteins invovled in energy production and conversion and lipid transport and metabolism of gut microorganisms were increased after two-week exposure 0.5 g/L TET. The change of microbial community increased metabolic activity that the dietary complex carbohydrates could be digested and subsequently fermented into easy absorption materials. The nutrient affects a series of host processes, including energy utilization, lipid synthesis and oxidative lesions. After two-week recovery, intestinal microbial community recovered from effects of low-dose TET exposure. But in the the microbial community high-dose group could not recover.In summary, TET exposure caused lesions in the mice liver tissue, and disturbed urine and serum metabolism in mice. Meanwhile, TET exposure improved the abundance of intestinal ARGs and MGEs, and increased potential environmental health risks. Intestinal microbiota played an important role in the adverse effects induced by TET exposure. The toxic effects and antibiotic resistance risk of high dose of TET exposure could be persistent. |
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