Oral mucosal injury in hematopoietic stem cell recipients:Emphasis on inflammation and the oral microbiome

The aim of this thesis was to describe oral complications associated with hematopoietic stem cell transplantation (HSCT) and to investigate the contribution of oral microorganisms in the pathogenesis of oral mucositis, a debilitating complication in HSCT recipients. First, the literature was reviewed regarding oral mucositis, graft versus host disease (GvHD), infections and dysgeusia, focusing on the inflammatory pathways and inflammatory mediators. Subsequently, we explored the influence of Candida spp. on epithelial cell migration in vitro to elucidate their possible role in oral mucositis. We concluded that C. glabrata and C. kefyr strongly inhibit the migration of oral epithelial cells, thereby hampering mucosal repair mechanisms. In chapter 4, we aimed to further unravel the role of microorganisms in mucositis and found that C. glabrata , C. kefyr , and P. gingivalis had no effect on the reproductive capacity of the oral epithelial cells. High concentrations of these microorganisms did however, lower the metabolic activity of the oral epithelial cells. In the next chapter, we longitudinally assessed the dynamic changes in the oral microbiome relative to the development of ulcerative oral mucositis in autologous HSCT recipients. We observed that high-dose chemotherapy induced significant, but reversible changes in the oral microbiome accompanied by a significant and reversible decrease in microbial diversity. In the final chapter, we aimed at informing the dental practitioner about the recognition and management of oral chronic GvHD (cGvHD), a common complication of allogeneic HSCT.