Primary hyperparathyroidism is a common endocrine disorder marked by excessive secretion of parathyroid hormone, which can lead to varying degrees of bone loss and fracture risk. The reasons behind this variability have been unclear.
A study led by Professor Roberto Pacifici, published on May 25 in Bone Research, investigated whether the gut microbiome could explain differences in skeletal outcomes among patients with primary hyperparathyroidism. Researchers analyzed stool samples, bone density measurements, and immune-cell profiles from 50 individuals with the condition. They found that the composition of gut microbes was closely associated with both bone health and immune activity.
To determine if the microbiome directly affects bone loss, researchers performed fecal microbiota transfer experiments. They transplanted gut bacteria from patients with osteoporosis, osteopenia, or normal bone density into germ-free mice. Mice receiving microbiota from osteoporotic patients developed greater bone loss and higher levels of inflammatory immune cells compared to those receiving transplants from healthier individuals. "We show that the extent to which primary hyperparathyroidism impacts the human skeleton correlated with the abundance of Bifidobacterium longum, a taxon that we show to induce the expansion of both intestinal and BM TNF+ T cells and Th17 cells," said Prof. Pacifici.
The study identified tumor necrosis factor-producing T cells and T helper 17 cells as key mediators linking specific gut bacteria to skeletal deterioration. Higher levels of these immune cell populations were consistently associated with lower bone density in both human subjects and recipient mice.
Further analysis showed that increased abundance of Bifidobacterium longum was linked to elevated expression of inflammatory molecules such as TNF and IL-17—both known promoters of bone resorption—and poorer skeletal structure in experimental models. Mechanistic experiments demonstrated that colonization with Bifidobacterium longum stimulated expansion and migration of these immune cells from intestine to bone marrow, where they released factors accelerating bone breakdown under high parathyroid hormone conditions.
Researchers concluded there were no significant differences in overall microbial community composition between patient groups; instead, susceptibility appeared tied to specific bacterial species like Bifidobacterium longum rather than broad changes in diversity or richness. "These findings confirmed that the presence of Bifidobacterium longum in the gut microbiome allows PTH to cause the expansion and migration of TNF+ T cells and Th17 cells and to induce bone loss," concluded Prof. Pacifici.
The results suggest potential for developing biomarkers based on microbial signatures for predicting osteoporosis risk among these patients as well as exploring targeted interventions such as precision probiotics or other strategies aimed at modifying relevant microbes.
