Blood Microbiota and Type 2 Diabetes: The Role of LPS and 16S rRNA in Altered Glucose Metabolism 公开

Konar, Martha (Spring 2021)

Permanent URL: https://etd.library.emory.edu/concern/etds/bk128c066?locale=zh
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Abstract

Evidence suggests bacterial translocation from the gastrointestinal tract into the systemic circulation may contribute to the inflammatory processes associated with the development of type 2 diabetes. To evaluate this relationship, a systematic literature review was conducted using observational studies published within the past 15 years that measured LPS or 16S rRNA levels in the blood of human adults and assessed the association between this exposure and an outcome of type 2 diabetes. A search of the published data identified 11 studies that met the established criteria from 1,224 records. Analysis of the data revealed that while many studies suggest a relationship may be present, aspects of study design and methodology limited the validity of the results and the relationship between blood microbiota and type 2 diabetes remains unclear. To determine whether bacteria may in fact have a role in this process, additional research will be needed that builds upon the lessons learned. In particular, combining large, longitudinal studies with random sampling, full reporting of and adjustment for confounding variables, newer detection methods using molecular-based techniques and type 2 diabetes diagnostic criteria that are testing-based are the key recommendations that will allow us to better ascertain the relevance of this unique exposure and its affect on glucose metabolism.

Table of Contents

I. Introduction 1

A. Introduction and Rationale 1

B. Problem Statement 9

C. Purpose Statement 15

D. Research Questions 16

E. Significance Statement 16

F. Definition of Terms 19

II. Literature Review 20

A. Exploring Host-Microbiome Interactions 20

B. Relationship Between Diet and Gut Microbiota 23

C. Relationship Between Gut Microbiota and Type 2 Diabetes 27

D. LPS, Intestinal Absorption, and the Limulus Amoebocyte Lysate (LAL) Assay 29

E. 16S rRNA, Bacterial Translocation, and Molecular-Based Techniques 32

III. Methods 37

A. Inclusion Criteria 37

B. Exclusion Criteria 37

1. Population 37

2. Exposure 37

3. Outcome 40

4. Study Design 40

C. Search Methods 40

D. Search Process 42

E. Extraction 44

F. Analysis 45

G. Reporting 45

H. Limitations 45

I. Ethical Considerations 46

IV. Results 47

A. Cross Sectional Studies Examining the Relationship Between LPS and Type 2 Diabetes 47

1. Descriptive Statistics 47

2. Measurement of LPS 51

3. Measurement of Type 2 Diabetes-Related Indices 55

4. Associations Between LPS and Type 2 Diabetes-Related Indices 57

B. Prospective Cohort Studies Examining the Relationship Between LPS and Type 2 Diabetes 59

1. Descriptive Statistics 60

2. Measurement of LPS 60

3. Measurement of Type 2 Diabetes-Related Indices 66

4. Associations Between LPS and Type 2 Diabetes-Related Indices 66

C. Studies Examining the Relationship Between 16S rRNA and Type 2 Diabetes 68

1. Descriptive Statistics 68

2. Measurement of 16S rRNA 72

3. Measurement of Type 2 Diabetes-Related Indices 75

4. Associations Between 16S rRNA and Type 2 Diabetes-Related Indices 75

V. Discussion 78

A. Study Design 78

B. Population 79

C. Assessment of LPS and 16S rRNA Levels 82

D. Assessment of Type 2 Diabetes 86

E. Final Recommendations 88

References 90

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