Unusual oral mucosal microbiota after hematopoietic cell transplantation with glycopeptide antibiotics: potential association with pathophysiology of oral mucositis

Abstract

Severe oral mucositis occurs frequently in patients receiving hematopoietic stem cell transplantation (HCT). Oral mucosal bacteria can be associated with progression of oral mucositis, and systemic infection may occur via ulcerative oral mucositis. However, little information is available regarding the oral microbiota after HCT. Here, PCR-denaturing gradient gel electrophoresis (DGGE) was performed to characterize the oral mucosal microbiota, which can be affected by antibiotics, before and after HCT. Sixty reduced-intensity HCT patients were enrolled. Three patients with the least antibiotic use (quinolone prophylaxis and/or β-lactam monotherapy group) and three patients with the most antibiotic use (β-lactam-glycopeptide combination therapy group) were selected. Bacterial DNA samples obtained from the oral mucosa before and after HCT were subjected to PCR-DGGE. The trajectory of oral mucositis was evaluated. The oral mucosal microbiota in the β-lactam-glycopeptide combination therapy group was different from that in the quinolone prophylaxis and/or β-lactam monotherapy group, and Staphylococcus spp. and Enterococcus spp. were identified. Lautropia mirabilis was dominant in one patient. Ulcerative oral mucositis was observed only in the β-lactam-glycopeptide combination therapy group. In conclusion, especially with the use of strong antibiotics, such as glycopeptides, the oral mucosal microbiota differed completely from that under normal conditions and consisted of Staphylococcus spp., Enterococcus spp., and unexpectedly L. mirabilis. The normal oral microbiota consists not only of bacteria, but these unexpected bacteria could be involved in the pathophysiology as well as systemic infection via oral mucositis. Our results can be used as the basis for future studies in larger patient populations.