Primary hyperparathyroidism (PHPT) is a common endocrine disorder characterized by excessive secretion of parathyroid hormone (PTH). Some patients experience significant bone loss and increased fracture risk, while others with similar hormone levels maintain relatively healthy bones. So far, the reasons for this variation remain unclear.
Now, a new study led by Professor Roberto Pacifici has been published in the journal May 25, 2026. bone researchResearchers investigated whether the gut microbiota could explain differences in skeletal outcomes among PHPT patients. The research team analyzed stool samples, bone density measurements, and immune cell profiles from 50 patients with PHPT. Their findings revealed that the composition of the gut microbiome is closely linked to bone health and immune activity.
To test whether the microbiome directly influences bone loss, researchers conducted a fecal microbiota transfer (FMT) experiment in which the gut microbiota of PHPT patients with osteoporosis, osteopenia, or normal bone density was transplanted into germ-free mice. Notably, mice that received microbiota from patients with osteoporosis had greater bone loss and increased levels of inflammatory immune cells compared to mice that received microbiota from patients with healthier bones. “We showed that the extent to which primary hyperparathyroidism affects the human skeleton is correlated with the abundance of Bifidobacterium longum, a taxon that has been shown to induce proliferation of TNF+ T cells and Th17 cells in both the intestinal tract and BM.” Professor Pacifici explained.
This study identified two important immune cell populations, tumor necrosis factor (TNF)-producing T cells and T helper (Th17) cells, as important mediators linking the gut microbiota and bone deterioration. The researchers found that high levels of these immune cells were consistently associated with decreased bone density in both PHPT patients and recipient mice transplanted with microbiota from these patients. These findings suggest that immune activation may serve as an important biological bridge between gut bacteria and skeletal health.
To further investigate this link, the researchers analyzed the relationship between specific bacterial species and immune cell activity. Among the bacterial species identified are Bifidobacterium longum It has emerged as a particularly influential microorganism. Through statistical analysis, Bifidobacterium longum was associated with increased expression of inflammatory molecules TNF and IL-17, both of which are known to promote bone resorption. These inflammatory signals were found to be associated with decreased bone density and worsening of bone structure in PHPT patients in experimental models.
The team then conducted a series of mechanistic experiments to determine: Bifidobacterium longum It can directly affect bone health. They used a germ-free mouse model to Bifidobacterium longum Stimulated the proliferation of TNF-producing T cells and Th17 cells in the intestine and bone marrow. The bacteria also facilitated the migration of these immune cells from the intestines to the bone marrow, where they released inflammatory factors that can promote bone destruction. When exposed to elevated levels of parathyroid hormone, mice Bifidobacterium longum This provides direct evidence that this bacterial species can amplify the skeletal effects of PHPT.
Interestingly, the researchers found no significant differences in overall microbiome composition between patients with osteoporosis, osteopenia, or normal bone density. Rather, susceptibility to bone loss appears to depend on the abundance of specific bacterial species rather than broad changes in the microbial community. This finding highlights the importance of identifying functionally related microorganisms that can influence disease outcome. Taken together, these results suggest that the gut microbiome is not simply associated with skeletal health, but may actively determine the severity of bone loss in patients with PHPT. identification of Bifidobacterium longum Immune cell signatures associated with osteoporosis risk also raise the possibility of developing microbiome-based biomarkers to identify patients most vulnerable to skeletal complications. “These findings confirmed that the presence of Bifidobacterium longum in the gut microbiome allows PTH to trigger the proliferation and migration of TNF+ T cells and Th17 cells and induce bone loss.” Professor Pacifici concluded:
The findings not only improve risk prediction but also present new treatment opportunities. Targeted microbiome interventions, including selective microbial modulation, antibiotics, precision probiotics, or other microbiota-directed strategies, may ultimately help prevent or reduce bone loss in patients with PHPT. Such an approach could complement existing treatments and pave the way for a more personalized management of metabolic bone diseases.
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DOI: https://doi.org/10.1038/s41413-026-00529-1
