Title Page
Contents
I. Introduction 9
II. Materials and Methods 11
Patients 11
Stool sample 16s rRNA analysis 11
Animal experiment 12
Strain preparation 13
Histopathology 14
Blood chemistry test 14
Enzyme linked immunosorbent assay (ELISA) 14
Oral glucose tolerance test 15
Real time - quantitative polymerase chain reaction (RT-qPCR) 15
Western blotting 16
RNA-seq microarray analysis 17
Statistical Analysis 18
III. Results 19
1. Patient characteristics for liver disease progression 19
2. Alterations of the human gut microbiome composition in nonalcoholic fatty liver disease 20
3. L. acidophilus and P. dorei treat liver damage by regulating gut-liver axis 23
4. Administration of L. acidophilus and P. dorei modulates gut microbiome dysbiosis 28
5. L. acidophilus improves blood glucose in a diabetes mice model 31
6. L. acidophilus inhibits lipogenesis and gluconeogenesis in an AMP-activated protein kinase (AMPK)-dependent manner 36
7. RNA microarray analysis in hepatic identifies new genes involved in gluconeogenesis 40
8. The therapeutic effect of L. acidophilus is affected by the gut microbiome 42
IV. Discussion 49
V. References 54
Abstract Korean 60
Abstract English 62
Table 1. Real time PCR primer sequence. 16
Table 2. Flowchart of liver disease patient enrollment. 19
Table 3. Baseline characteristics of the participants in the study. 20
Table 4. Flowchart of diabetes mellitus patient enrollment. 44
Table 5. Baseline characteristics of the participants in the study. 44
Figure 1. Human gut microbiota was analyzed by 16s rRNA Sequencing. 23
Figure 2. Effect of strains on hepatic steatosis and liver function in the western diet model. 26
Figure 3. Effects of strains on gene expression of inflammation and lipid metabolism in the liver. 27
Figure 4. Animal stool analysis in Western diet model. 31
Figure 5. Effect of L. acidophilus on liver histopathological changes in ob/ob model. 34
Figure 6. Effect of L. acidophilus on liver function and glucose production ability. 34
Figure 7. Effects of L. acidophilus on gene expression of lipid metabolism and gluconeogenesis in the liver. 39
Figure 8. RNA microarray analysis isolated from liver tissue. 42
Figure 9. Human gut microbiota for diabetes mellitus was analyzed by 16s rRNA Sequencing. 46
Figure 10. Animal stool analysis in diabetes mice model. 47