Next-generation sequencing reveals that loss of gut microbiota diversity after allo-HSCT is associated with acute GvHD and increased mortality. Early broad-spectrum antibiotic use is a major risk factor for intestinal dysbiosis, often accompanied by dominance of Enterococcus faecium (Efm). In a long-standing collaboration between hematology and microbiology, our group aims to determine whether Efm dominance is merely an indirect indicator of intestinal dysbiosis or exerts direct pathogenic effects in GvHD pathophysiology by examining enterococcal impact on tissue inflammation and intestinal epithelial integrity, and by characterizing enterococcus-specific immunity. Ultimately, we seek strategies to mitigate Efm-driven GvHD, laying the groundwork for a potential clinical fecal microbiota transplantation (FMT) trial.
As a translational scientist, I focus on the role of the intestinal microbiome in the pathophysiology of acute GI GvHD, highlighting the impact of antibiotic use during allo-HSCT. By combining clinical observation, interpretation of patient data, and analysis of patient bio-samples, I aim to gain a deeper understanding of the pathophysiological mechanisms underlying acute GvHD and to improve patient outcomes.
Within the Collaborative Research Centre/Transregio (CRC/TRR) 221 innovative immune modulation strategies will be investigated to separate GvHD from GvL effects in order to enhance the safety and efficacy of allo-HSCT in the future.