Grant: Project Grant

Proton pump inhibitors (PPIs) are common medications used to treat acid reflux and heartburn. They are among the most prescribed drugs in older adults, particularly in postmenopausal females (PMF), who already face increased risk of bone loss due to low estrogen levels. Although PPIs are intended for short-term use (4-8 weeks), many females continue taking them for years. Long-term PPI use has been linked to a higher risk of fractures, and PPIs are also known to alter the gut microbiome-the community of bacteria living in our intestines that plays an important role in bone health. However, it remains unclear whether changes in the gut microbiome caused by PPIs directly contribute to bone weakness. It is also unknown whether even short-term PPI use can trigger early changes in bone health before fractures occur. This project will study 120 PMF aged 60-70, including long-term PPI users and PMF starting short-term therapy. By analyzing stool and blood samples, we will examine how PPI use affects gut bacteria, circulating metabolites, inflammation, and markers of bone turnover. These measurements will help identify biological patterns that signal increased fracture risk. In a second phase, we will use a validated laboratory model of the human gut, called SHIME to grow gut bacteria from selected participants and test whether substances produced by these microbes directly affect human bone cells. This will help determine whether PPI-related microbiome changes causally influence bone remodeling. Together, this research will clarify whether changes in gut bacteria caused by PPIs can lead to early bone weakening. By identifying PMF who show biological signs of increased bone breakdown, this work aims to support safer treatment decisions and help protect bone health as women age.