THE EFFECTS OF THE MICROBIOME IN ENDOCRINE VITAMIN D METABOLISM
Open Access
- Author:
- Bora, Stephanie Andrea
- Graduate Program:
- Immunology and Infectious Diseases
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- May 15, 2017
- Committee Members:
- Margherita Teresa-Anna Cantorna, Dissertation Advisor/Co-Advisor
Margherita Teresa-Anna Cantorna, Committee Chair/Co-Chair
Andrew David Patterson, Committee Member
K. Sandeep Prabhu, Committee Member
Connie J. Rogers, Outside Member - Keywords:
- Vitamin D
Biology
Microbiome
physiology
health
immunology
endocrine
antibiotics
metabolism - Abstract:
- Vitamin D insufficiency is associated with bone diseases like osteoporosis and immune- mediated disease like inflammatory bowel disease. Endocrine vitamin D metabolism is thought to be controlled by calcium intake and other hormones that interact to regulate mineral homeostasis, such as parathyroid hormone (PTH) from the parathyroid gland and fibroblast growth factor (FGF23) from bone. The gut microbiome consists of trillions of cells that have coevolved with their hosts to influence nutrition, metabolism, and immune function. There is evidence the microbiome regulates bone health, indicating a link between the gut microbiome and endocrine vitamin D metabolism. Using antibiotic treatments and colonization of germ free mice, I examined the effects of host-microbial interactions on regulation of endocrine vitamin D metabolism. My research showed disrupting the microbiome with antibiotics increased FGF23 and 25-hydroxyvitamin D, a stable vitamin D metabolite used as a marker of vitamin D status. These changes were dependent on signaling through toll-like receptors. Colonization of germ free mice decreased host FGF23, leading to increased levels of hormonal vitamin D and circulating calcium. In both antibiotics treated mice and colonized mice, changes in FGF23 and vitamin D metabolites were associated with changes in TNF-α. Together, the work presented in this dissertation suggests host sensing of the gut microbiome regulates FGF23 and endocrine vitamin D metabolism, both of which are critical for mineral homeostasis and bone health.