Title Page
ABSTRACT
Contents
CHAPTER Ⅰ. Gut Dysbiosis and Its Impact on Human Disease 13
ABSTRACT 14
INTRODUCTION 15
Ⅰ. Functions and contributions of gut microbial community 17
Ⅱ. Association between gut bacterial dysbiosis and diseases 18
Ⅲ. Human diseases influenced by the gut mycobiota 29
PERSPECTIVE 31
LITERATURE CITED 32
CHAPTER Ⅱ. Dysbiotic but nonpathogenic shift in the fecal mycobiota of patients with rheumatoid arthritis 43
ABSTRACT 44
INTRODUCTION 45
MATERIALS AND METHODS 48
Ⅰ. Sample collection 48
Ⅱ. DNA extraction from feces 48
Ⅲ. PCR amplification and sequencing 49
Ⅳ. Sequence processing and filtering 50
Ⅴ. Statistical analyses and visualization 51
Ⅵ. Microbial correlation networks 52
Ⅶ. Fungal strain cultivation 53
Ⅷ. DNA extraction and qualitative PCR (gel blotting of samples) 54
Ⅸ. Real-time quantitative PCR to quantify C. albicans abundance 55
RESULTS 56
Ⅰ. Descriptive statistics 56
Ⅱ. Fecal microbial community composition 59
Ⅲ. Fecal microbial diversity 67
Ⅳ. RA patient-associated bacterial and fungal OTUs 76
Ⅴ. Fecal bacterial-fungal associations 83
Ⅵ. Changes in the fecal fungal community in response to medication 88
Ⅶ. Fungal dysbiosis can be used for characterization of RA 94
DISCUSSION 97
LITERATURE CITED 101
초록 110
CHAPTER Ⅰ 11
Table 1. Alterations in gut bacterial abundance associated with human diseases 24
Table 2. Biotransformation of pharmaceuticals by gut microbiota 27
CHAPTER Ⅱ 11
Table 1. Characteristics of study participants. 57
Table 2. The medication for patients with RA. 58
Table 3. Results on permutational analysis of variance (PERMANOVA) 74
CHAPTER Ⅱ 12
Figure 1. Comparisons of the fecal bacterial community composition between HC and RA. 62
Figure 2. Fecal microbial community composition in healthy controls and patients with RA. 64
Figure 3. Comparisons of the fecal fungal community composition between HC and RA. 66
Figure 4. Differences in alpha diversity between HC and RA. 69
Figure 5. Ordination analysis of fecal bacterial and fungal communities in healthy controls and patients with RA. 71
Figure 6. Unconstrained principal coordinate analysis (PCoA) of bacterial and fungal communities between HC and RA. 73
Figure 7. Fecal bacterial OTUs affected by the dysbiosis of rheumatoid arthritis. 78
Figure 8. Fecal fungal OTUs affected by the dysbiosis of rheumatoid arthritis. 80
Figure 9. Microbial signatures associated with RA. 82
Figure 10. Interkingdom co-occurrence networks and hub nodes of fecal microbiota. 85
Figure 11. A comparison of the topological properties between microbial HC and RA networks. 87
Figure 12. Effects of medication on Candida abundance. 91
Figure 13. Agarose gel electrophoresis image of the C. albicans specific PCR products. 93
Figure 14. Analysis of core OTUs in fecal microbiota. 96