In parallel to our studies in healthy volunteers, the Byrd lab maintains and enjoys active collaboration with oncologists around the world, including Dr. Shahneen Sandhu at Peter MacCallum Cancer Centre in Melbourne, Australia. For the last several years, Dr. Sandhu has led the observational trial MicroMac with the objective to characterize changes in the gut microbiomes of 150 patients with melanoma before and after the commencement of antibiotics and/or corticosteroids given for the treatment of immune-related adverse events (irAEs) and infections that occur during standard of care immunotherapy.
We hypothesize that detectable changes in microbiome composition will precede irAEs, and these dysbioses revert upon irAE cessation. To test this hypothesis, to date we have sequenced hundreds of longitudinal stool samples from patients, pairing this with extensive clinical metadata, including adverse event occurrences, usage of concomitant medications (e.g. antibiotics and corticosteroids), and therapeutic outcomes, for each patient. These studies will provide an unprecedented insight into long term microbial dynamics during the course of checkpoint inhibitor therapy and how this correlates to concomitant medication usage, adverse events, and efficacy. Moving forward, we will extend this work from using irAE as clinical models of induced autoimmunity, to autoimmune diseases, particularly those where aberrant immune reactivity to commensal microbes is a hallmark, e.g. Type 1 Diabetes, Rheumatoid arthritis and Inflammatory Bowel Disease.
Additional Research Projects
Steady State Microbiome and Metabolome
