The human microbiome and bone healing: observations and interventions in infectious and non-infectious bone disease

The successful candidate will be jointly hosted by the AO Research Institute Davos, and the Swiss Institute of Asthma and Allergy (SIAF), Davos.

An ever-growing number of studies have demonstrated an interplay between the composition of our microbiomes and numerous disease states, for example colorectal cancer and inflammatory bowel disease. It is also becoming increasingly evident that the gut microbiome can powerfully influence bone health. An important question, of relevance to orthopedic patients with osteomyelitis or fracture related infection (FRI), is whether prolonged therapeutic antibiotic regimens may negatively influence the microbiome and what the knock-on effects this may have with regards to bone healing. The possibility that the microbiome and bone healing may be impacted in a deleterious way by antibiotic therapy has not been studied to date, and will be the focus part 1 of this project.

In part 2, we will advance this line of investigation by investigating how we can influence the composition of the microbiome to the benefit of the patient with regards to bone loss and bone healing. By supplementing the microbiome with probiotic bacteria, others have shown that this can attenuate bone loss in preclinical models of post-menopausal osteoporosis (PMO) and Type 1 diabetes (T1D). In a recent study in our laboratories, we investigated the bioactivity of probiotic-derived factors and determined them to be potent modulators of bone health through immunoregulatory mechanisms. This suggests that microbiome-based strategies may provide a novel approach for preventing diseases associated with chronic inflammation, such as PMO and T1D. Therefore, in the second part of this study we will investigate the efficacy and mechanisms of probiotic supplementation in vitro and in preclinical murine models of PMO and T1D.