Bacterial specificity of the gut microbiome predicts bone density in primary hyperparathyroidism

Primary hyperparathyroidism causes mild-to-severe bone loss, but the reason for this heterogeneity is unclear. We investigated the role of the microbiome in 50 primary hyperparathyroidism patients. Microbiome transfers from primary hyperparathyroidism patients with and without osteoporosis to germ-free mice replicated the human bone phenotype and regulated TNF⁺ T cells and Th17 cells in mice. Accordingly, circulating TNF⁺ T cells and Th17 cells and TNF/IL17 production predicted bone density in primary hyperparathyroidism patients. Bifidobacterium longum, TNF⁺ T cells, and Th17 cells were mediators of bone loss in primary hyperparathyroidism patients, while Bifidobacterium longum supplementation caused PTH to expand TNF⁺ T cells and Th17 cells and induce bone loss in mice. Our findings link Bifidobacterium longum-induced TNF⁺ T cells and Th17 cells to bone loss in patients with primary hyperparathyroidism. Bifidobacterium longum abundance may determine the skeletal phenotypes of patients with primary hyperparathyroidism and allow prediction of their risk of bone loss. Microbiome modifications by antibiotics or precision probiotics might offer novel preventive approaches for the skeletal complications of primary hyperparathyroidism.