Oral Inflammation and Microbiome Dysbiosis Exacerbate Chronic Graft-Versus-Host Disease

Authors

Yui Kambara
Hideaki Fujiwara
Akira Yamamoto
Kazuyoshi Gotoh
Shuma Tsuji
Mari Kunihiro
Tadashi Oyama
Toshiki Terao
Ayame Sato
Takehiro Tanaka
Daniel Peltier
Keisuke Seike
Hisakazu Nishimori
Noboru Asada
Daisuke Ennishi
Keiko Fujii
Nobuharu Fujii
Ken-Ichi Matsuoka
Yoshihiko Soga
Pavan Reddy
Yoshinobu Maeda

Language

English

Publication Date

2-20-2025

Journal

Blood

DOI

10.1182/blood.2024024540

PMID

39693612

PMCID

PMC11867138

PubMedCentral® Posted Date

10-20-2024

PubMedCentral® Full Text Version

Post-print

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.

Keywords

Graft vs Host Disease, Animals, Dysbiosis, Mice, Hematopoietic Stem Cell Transplantation, Humans, Male, Female, Inflammation, Chronic Disease, Mice, Inbred C57BL, Mouth, Stomatitis, Microbiota, Gastrointestinal Microbiome, Middle Aged, Adult

Published Open-Access

yes

Recommended Citation

Kambara, Yui; Fujiwara, Hideaki; Yamamoto, Akira; et al., "Oral Inflammation and Microbiome Dysbiosis Exacerbate Chronic Graft-Versus-Host Disease" (2025). Faculty, Staff and Students Publications. 6348.
https://digitalcommons.library.tmc.edu/baylor_docs/6348