The gut microbiota in personalized treatment of osteoporosis

Osteoporosis constitutes a significant public health concern.

We were first to demonstrate that the gut microbiota (GM) regulates bone mass and that treatment with probiotics prevents against postmenopausal bone loss.

In this proposal, we explore the GM in personalized fracture prediction and treatment of osteoporosis.To identify GM signatures improving fracture prediction, we will evaluate the associations between the GM composition and incident fractures in large well characterized cohorts, followed by machine learning procedures.

Their clinical usefulness beyond the currently used fracture prediction tools will be determined in an independent cohort.To find candidate probiotics with enhanced bone protective effect, we will identify bacteria with (i) high synthesis of bone protective short chain fatty acids identified by in silico prediction, (ii) associated with bone health in humans or (iii) protecting against age-dependent bone loss in mice.

The bone-sparing effect of the candidate probiotics will be evaluated in mouse osteoporosis models.We recently showed that certain probiotics protect against postmenopausal bone loss but the treatment response varied.

Determinants of the probiotic response on bone mass in that study will be identified by comparing the baseline GM composition in the high vs low responders.These translational projects, on the role of the GM for bone health, will result in improved personalized prevention, diagnosis, and treatment of osteoporosis.