Date of Completion

4-1-2019

Embargo Period

3-6-2020

Keywords

microbiome, aging, diabetes

Major Advisor

George Weinstock

Co-Major Advisor

George Kuchel

Associate Advisor

Derya Unutmaz

Associate Advisor

Julia Oh

Associate Advisor

Laura Haynes

Associate Advisor

Blanka Rogina

Field of Study

Biomedical Science

Degree

Doctor of Philosophy

Open Access

Open Access

Abstract

The human body is cohabitated with large number of microorganisms, which potentially influence the health conditions of the host. Dynamic interactions between microbiome and host are critical for this cohabitation relationship. Among human population, the composition of microbiome shows clear interpersonal variations and intrapersonal plasticity, with patterns and mechanisms that are currently unclear. In the first part of this thesis, we explored the human microbiome variations in relation to healthy aging, aimed to understand if microbiome imbalance, or dysbiosis, is a common phenotype of older adults regardless of the age-related diseases. In the second part, we expanded our investigation on the microbiome plasticity to individuals with prediabetes condition, which is more common in older adults. We confirmed that microbiome composition in healthy adults was not significantly different based on their chronological age but were dramatically altered among some individuals at risks metabolic diseases. More importantly, we identified a concomitant change of serum cytokines and the gut microbiome among individuals, which imply a causational relationship between microbiome, immune system and the metabolic diseases. This thesis explored the microbiome variation in both healthy individuals and patients with prediabetes, demonstrated the development of dysbiosis under the risk for metabolic diseases, and potentially revealed a new microbiome-related etiology for metabolic diseases.

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