Antibiotics-induced Mice Microbial Alteration And Their Relationship With Host Metabolic Profiles

Mammalian and its symbiotic gut microbiota have been regarded as superorganism with determine a super complex and dynamic ecosystem. Bacteroidetes, Firmicutes, and other species, are the dominant phyla in the mammalian gut microbial community, which co-develop with the host throughout their lifetime and influence host health and disease status remarkably. Unbalanced microbial colonies have been reported to disturb the physiological homeostasis, which leading to various diseases such as colon cancer, inflammatory bowel disease, irritable bowel syndrome, obesity, diabetes, cardiovascular disease, autism and allergic asthma. Understanding the composition and metabolism of the gut microbiota were the basic mechanism of gut microbiota interaction with the host. Although there is a global understanding of gut microbiota, our knowledge of which bacterial species synthesize which metabolites is currently limited. In the thesis, we try to explore the relationship between the gut microbiota and host metabolism in details.In current works, we treated mice with gentamicin and/or ceftriaxone and monitored changes in gut microbiota and host metabolites using16S rRNA gene polymerase chain reaction (PCR)-denaturing gradient gel electrophoresis (DGGE). And we employed1H nuclear magnetic resonance (NMR) techniques to investigate mice fecal extracts and urinary metabolic profiling. We found that gut microbial composition and host metabolites were different under different antibiotics at low or high dosage. In addition, the correlation between the gut microbial composition and host metabolites with a view to probe the function of gut microbiota were also paid attention to in current works.First, the changes of gut microbiota composition are associated with different antibiotics. Barnesiella, Prevotella, and Alistipes levels were shown decrease as a result of the antibiotic treatment, whereas Bacteroides, Enterococcus and Erysipelotrichaceae incertae sedis, and Mycoplasma abundance increased after gentamicin and ceftriaxone treatment.We found that Barnesiella is a common and sensitive gut microbiota in BALB/c mice and can be used as an indicator for assessing the balance of the gut microbial community. Obligatory anaerobic bacteria levels were shown to decrease as a result of the antibiotic treatment, whereas levels of facultative anaerobic bacteria. In addition, bacteria were sensitive to the environment during the recolonization.Second, the levels of short chain fatty acids (SCFAs), amino acids (AAs) and primary bile acids decreased in feces after antibiotics treatment, while the levels of oligosaccharides, D-pinitol, choline and secondary bile acids (deoxycholic acid) increased. This suggests suppressed bacterial fermentation, protein degradation and enhanced gut microbial modification of bile acids. In addition, there was a strong correlation between fecal SFCAs, AAs and levels of Bacteroides, Barnesiella, Alistipes and Prevotella. These metabolites showed important impact on host. Understanding the correlation between the gut microbiota and host metabolism would contribute to promote human health.Last, NMR-based metabonomics was employed to show the impact on urine profiles in mice. The levels of the most of the phenolic acids, methylamines and the products of choline degradation were decreased in urine after antibiotics treatment, while citrulline, creatinine, betaine and D-pinitol were increased. This suggests metabolism of phenolic acids, choline degradation and urea cycle in the host were interrupted after antibiotics treatment.In summary, this thesis investigated gut microbiota composition and host metabolism after antibiotics treatment. Exploring the metabolic phenotypes and the gut microbiota functionalities is of particular importance for optimizing therapeutic strategies, and developing potential microbiota-based disease preventions and therapeutic interventions.