Oral inflammation and microbiome dysbiosis exacerbate chronic graft-versus-host disease

The oral microbiota, second in abundance to the gut, is implicated in chronic systemic diseases, but its specific role in graft-versus-host disease (GVHD) pathogenesis has been unclear. Our study finds that mucositis-induced oral dysbiosis in patients after hematopoietic cell transplantation (HCT) associated with increased chronic GVHD (cGVHD), even in patients receiving posttransplant cyclophosphamide. In murine HCT models, oral dysbiosis caused by bilateral molar ligatures exacerbated cGVHD and increased bacterial load in the oral cavity and gut, with Enterococcaceae significantly increasing in both organs. In this model, the migration of Enterococcaceae to cervical lymph nodes both before and after transplantation activated antigen-presenting cells, thereby promoting the expansion of donor-derived inflammatory T cells. Based on these results, we hypothesize that pathogenic bacteria increase in the oral cavity might not only exacerbate local inflammation but also enhance systemic inflammation throughout the HCT course. Additionally, these bacteria translocated to the gut and formed ectopic colonies, further amplifying systemic inflammation. Furthermore, interventions targeting the oral microbiome mitigated murine cGVHD. Collectively, our findings highlight the importance of oral dysbiosis in cGVHD and suggest that modulation of the oral microbiome during transplantation may be an effective approach for preventing or treating cGVHD.

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Publication Details

Journal
Blood
Published
2024-12-18
DOI
https://doi.org/10.1182/blood.2024024540
Citations
11
Primary Topic
Oral health in cancer treatment
Type
article
Field-Weighted Citation Impact
4.61

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article

Oral inflammation and microbiome dysbiosis exacerbate chronic graft-versus-host disease

Daniel Peltier, Kazuyoshi Gotoh, Nobuharu Fujii, Toshiki Terao et al.
11 citations
Blood
Oral health in cancer treatment
4.61
article

Oral inflammation and microbiome dysbiosis exacerbate chronic graft-versus-host disease

Daniel Peltier, Kazuyoshi Gotoh, Nobuharu Fujii, Toshiki Terao, Ken‐ichi Matsuoka, Yui Kambara, Noboru Asada, Keisuke Seike, Yoshinobu Maeda, Mari Kunihiro, Tadashi Oyama, Ayane Sato, Takehiro Tanaka, Daisuke Ennishi, Akira Yamamoto, Pavan R. Reddy, Yoshihiko Soga, Keiko Fujii, Shuma Tsuji, Hisakazu Nishimori, Hideaki Fujiwara
article en
11 citations

Abstract

The oral microbiota, second in abundance to the gut, is implicated in chronic systemic diseases, but its specific role in graft-versus-host disease (GVHD) pathogenesis has been unclear. Our study finds that mucositis-induced oral dysbiosis in patients after hematopoietic cell transplantation (HCT) associated with increased chronic GVHD (cGVHD), even in patients receiving posttransplant cyclophosphamide. In murine HCT models, oral dysbiosis caused by bilateral molar ligatures exacerbated cGVHD and increased bacterial load in the oral cavity and gut, with Enterococcaceae significantly increasing in both organs. In this model, the migration of Enterococcaceae to cervical lymph nodes both before and after transplantation activated antigen-presenting cells, thereby promoting the expansion of donor-derived inflammatory T cells. Based on these results, we hypothesize that pathogenic bacteria increase in the oral cavity might not only exacerbate local inflammation but also enhance systemic inflammation throughout the HCT course. Additionally, these bacteria translocated to the gut and formed ectopic colonies, further amplifying systemic inflammation. Furthermore, interventions targeting the oral microbiome mitigated murine cGVHD. Collectively, our findings highlight the importance of oral dysbiosis in cGVHD and suggest that modulation of the oral microbiome during transplantation may be an effective approach for preventing or treating cGVHD.

BloodVol. 145(8)
Indiana University Health (US), Okayama University (JP), Baylor College of Medicine (US), Okayama University Hospital (JP), Children's Cancer Center (US), Indiana University – Purdue University Indianapolis (US)
Daiichi Sankyo Foundation of Life Science, Yakult Bio-Science Foundation, National Institutes of Health, Japan Society for the Promotion of Science, National Heart, Lung, and Blood Institute, Daiichi Sankyo Europe
Good health and well-being
Openalex Percentile: Top 4%
Oral health in cancer treatment
4.61
DOIOpen Access PDFOpenAlex
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