Chemotherapy/radiation treatment during conditioning damages intestinal epithelium resulting in systemic exposure to microbial products normally sequestered in the intestinal lumen, in addition to a marked cytokine release which we have previously published. These microbial products can influence graft-versus-host disease (GVHD) and transplant outcome. Numerous approaches targeting the gut microbiome to harness GVHD (e.g. gut decontaminating antibiotics, introduction of beneficial bacteria or targeting anaerobic bacteria) have been attempted with some effect but there is no consensus between bone marrow transplant physicians. The main limitation with these studies has been the reliance on microbiological cultures to characterize the flora. This project will employ a culture-independent technique, 16S ribosomal RNA gene sequencing to address the following aims using pre-clinical models of allogeneic stem cell transplantation (allo-SCT).
1) Characterize the microbial diversity in the gut during homeostasis and following allo-SCT; 2) Assess the effect of IL-6 inhibition on the microbiota of the gastrointestinal tract during acute GVHD.
Outcome & significance
This project will provide valuable insight into the role of the microbiome during transplantation that may inform of new strategies that could be adopted to protect against unrestrained immune activation and GVHD.
- This project would be suitable for Honours students and flexible for clinical students.