Microbiota dependent bone loss in primary hyperparathyroidism

Primary hyperparathyroidism (PHPT) causes mild-to-severe bone loss, but the reason for this heterogeneity is unclear. We explored the role of the gut microbiome in 39 PHPT patients. Microbiome transfers from PHPT patients with and without osteoporosis to germ-free mice replicated the human bone phenotype and regulated TNF+ T-cells and Th17 cells in mice. Bifidobacterium longum (BL), TNF+ T-cells and Th17 cells were key mediators of bone loss in PHPT patients. Accordingly, circulating TNF+ T-cells and Th17 cells and their TNF/IL17 production predicted bone density in PHPT patients. Moreover, BL caused PTH to expand TNF+ T-cells and Th17 cells and induce bone loss in mice. Our findings link BL-induced TNF+ T-cells and Th17 cells to bone loss in PHPT patients. BL abundance may determine the skeletal phenotypes of PHPT patients and allow to predict the risk of bone loss. Microbiome modifications by antibiotics or probiotics might offer novel preventive approaches for PHPT-induced skeletal complications.