Pacifici Lab

Microbiome and Estrogen

Using germ-free mice, antibiotic treated mice and stool transfer techniques, we are investigating the mechanism by which estrogen deficiency alters gut permeability, immune cell activation in the gut, the trafficking of lymphocytes from the gut to the bone marrow, and the components of the gut microbiota that are relevant for bone loss.

Microbiome and PTH

We have shown primary hyperparathyroidism in humans and continuous PTH (cPTH) treatment in mice induces bone loss by expanding Th17 cells and inducing IL-17 production. By contrast, intermittent PTH (iPTH) treatment stimulates bone formation by expanding Tregs and inducing the release of Wnt10b by CD8+ T cells via a Treg mediated mechanism. We are currently investigating how the gut microbiome mediate the effects of cPTH and iPTH on Th17 differentiation and Treg differentiation.

Role of the microbiome on bone mass heritability

Bone density is, in large part, an inheritable trait. However, genetics explains only part of bone density variability. The composition of the microbiome is shaped in children by cohabitation. We are conducting co-housing experiments and stool, transfer experiments to determine the contribution of the gut microbiome to the bone mass heritability.

Role of the microbiome in fracture repair

Depletion of the gut microbiome impairs fracture healing in mice. We are investigating how the gut microbiome affects the inflammatory phase of fracture repair. Specifically, we are examining how the gut microbiome regulates the trafficking of T cells from the small intestine to the callus tissue and the production of inflammatory cytokines in the callus.

Mechanism of action of probiotics in bone

We have shown that probiotics prevent ovariectomy induced bone loss and increase bone mass in eugonadic mice. We are currently investigating the effects of probiotics on short-chain-fatty acids (SCFAs) and how SCFAs regulate Treg differentiation, Wnt10vb production and bone formation.

Roberto Pacifici, MD

Dr. Pacifici is the Garland Herndon Professor of Medicine and Director of the Division of Endocrinology, Metabolism and Lipids at Emory University, Atlanta GA. Dr. Pacifici is a graduate of the University of Perugia, Italy. He completed a fellowship in Endocrinology and Metabolism in the Division of Bone and Mineral Metabolism at the Washington University of St. Louis. He then joined the faculty of Washington University and was subsequently named the Shemberg Professor of Medicine. He has been at Emory as Division Director since 2002.

Dr. Pacifici is one of the founders of the field of osteoimmunology and an expert on the mechanism of action of estrogen and PTH in bone. He has been among the first to recognize that TNF and other inflammatory cytokines pay a critical role in the mechanism of action of estrogen and PTH in bone. Subsequent work from Pacifici and his collogues showed that T cells are major sources of TNF, RANKL, IL-17, Wnt10b and other factors by which estrogen deficiency and PTH regulate bone formation and bone resorption.  More recently, the Pacifici lab become focused on the regulatory effects of the gut microbiome on immune cells, which are relevant to the regulation of bone turnover and the mechanism of action of probiotics in bone.

• Jau-Yi Li, PhD
• Mingcan Yu, PhD
• Malik Tyagi Abdul
• Jonathan Adams, MS
• Subhashis Pal

We are actively seeking junior faculty and post-doctoral fellows to join our lab. For additional information, please e-mail Dr. Pacifici directly.