From the gut to bone: connecting the gut microbiota with Th17 T lymphocytes and postmenopausal osteoporosis

Abstract

Osteoporosis is a serious clinical problem that often follows the accelerated bone loss that occurs after the estrogen withdrawal of menopause. In order to better understand the mechanism that produces estrogen withdrawal-induced bone loss, Yu and Pal et al., as reported in this issue of the JCI, examined mice that underwent ovariectomy (OVX). In C57BL/6 mice with enhanced Th17 cells in gut tissue, the authors demonstrated that OVX increased migration of TNF-expressing Th17 cells from the gut to the bone marrow. Furthermore, they found that manipulation of the pathways by which lymphocytes migrate and home to bone marrow prevented the increase of TNF+, Th17 cells in bone marrow after OVX in mice and the trabecular, but not cortical, bone loss in this model. These results argue that interactions of the gut microbiota with the immune system are involved in the effects of estrogen withdrawal on trabecular bone.

Figure 1. Model for estrogen-withdrawal bone loss.

Loss of estrogen after OVX in mice enhances gut permeability, which causes increased release of gut-resident TNF⁺, Th17 cells. These T cells migrate to bone and enhance osteoclast-mediated trabecular bone resorption. It is also possible that enhanced release of gut bacterial products after OVX causes increased production of TNF⁺, Th17 cells in peripheral lymphoid organs such as liver-draining lymph nodes. TNF⁺, Th17 cells produced in response at these sites may also migrate to bone and affect trabecular bone resorption.