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

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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.

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Acknowledgments

PCR-DGGE analysis and sequence analysis were performed by a professional technical analysis service (Techno Suruga Lab Service, Shizuoka, Japan). We are grateful to Ms. Junko Tomita and Mr. Shunsuke Takahashi, technicians of Techno Suruga Laboratory Co., Ltd., for performing these analyses. We are also grateful to Ms. Motoko Nose, medical technologist of Clinical Laboratory, Central Clinical Department, Okayama University Hospital, Okayama, Japan, for the advice.

Funding

This study was partly supported by a Grant-in-Aid from JSPS KAKENHI Grant Number JP26462881 (to Y.S.), a Grant-in-Aid for the COE projects by MEXT, Japan, entitled “Center of excellence for molecular and gene targeting therapies with micro-dose molecular imaging modalities” (to Y.S.), and a Grant-in-Aid for the COE projects by Ministry of Health, Labour and Welfare, Japan, entitled “Designated regional hub hospital promoting hematopoietic stem cell transplantation” (to M.M.).

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Authors and Affiliations

  1. Division of Hospital Dentistry, Okayama University Hospital, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan

    Misato Muro, Yoshihiko Soga & Tomoko Higuchi

  2. Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan

    Misato Muro, Kota Kataoka, Daisuke Ekuni & Manabu Morita

  3. Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan

    Yoshinobu Maeda

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  1. Misato Muro
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  2. Yoshihiko Soga
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  3. Tomoko Higuchi
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  4. Kota Kataoka
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  5. Daisuke Ekuni
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  7. Manabu Morita
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Correspondence to Yoshihiko Soga.

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All subjects provided informed consent, and the study was approved by the Ethics Committee of Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences (Approval No. 902).

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The authors declare that they have no conflicts of interest.

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Muro, M., Soga, Y., Higuchi, T. et al. Unusual oral mucosal microbiota after hematopoietic cell transplantation with glycopeptide antibiotics: potential association with pathophysiology of oral mucositis. Folia Microbiol 63, 587–597 (2018). https://doi.org/10.1007/s12223-018-0596-1

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  • DOI: https://doi.org/10.1007/s12223-018-0596-1

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