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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.

The consequences of cancer therapy for oral health were studied. The effects of irradiation to the head and neck area for the protein composition of parotid saliva were mapped. It was found that irradiation to the head and neck area likely altered the gland tissues resulting in a change in the protein composition of parotid saliva. Furthermore, the role of the oral microflora in the course of oral mucositis and systemic complications after hematopoietic stem cell transplant (HSCT) were studied. Inflammation of the periodontium may be a risk factor for developing systemic infectious complications. Oral microorganisms are related to oral infectious complications since the microorganisms; the virus HSV-1, bacterial species that are associated with periodontitis P. gingivalis, P. micra, T. denticola and F. nucleatum and the yeasts C. glabrata and C. kefyr were positively associated with the presence of oral ulcerations in patients after HSCT. Some of these bacteria may prolong the existence of oral mucositis as they were able to hinder closure of a wound in oral epithelial cells in vitro. P. gingivalis was the most potent inhibitor of wound healing. From the known virulence factors that P. gingivalis possessed, the capsular polysaccharide and the gingipains influenced the capacity of P. gingivalis to hinder wound healing. Although microorganisms were considered to have only a minor role in oral mucositis, this thesis shows that they can influence the course of oral mucositis at least by inhibiting the healing of lesions.