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Study results implicate oral dysbiosis in chronic graft-vs-host disease (GVHD) and show that targeting the oral microbiome may improve GVHD outcomes.

Oral dysbiosis was associated with an increased incidence of chronic graft-vs-host disease (cGVHD) after hematopoietic cell transplantation (HCT), according to a study published in Blood.

“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,” researchers wrote.

Pavan Reddy, MD, and colleagues investigated associations between oral microbiome dysbiosis with outcomes in 230 patients who underwent allogeneic HCT. Among the patients, 132 had no or mild oral mucositis, and 98 had moderate-to-severe oral mucositis (grade 2 or 3).

Oral Mucositis Linked to Incidence of cGVHD

Moderate-to-severe oral mucositis was associated with a significantly higher incidence of cGVHD, the researchers found, and multivariate analysis confirmed it as an independent risk factor for cGVHD.

The study also included 71 patients who underwent haploidentical HCT with post-transplant cyclophosphamide at the same hospital. Among them, 47 had no or mild oral mucositis, and 24 had moderate-to-severe oral mucositis.

In that cohort, the cumulative incidence of cGVHD was significantly higher among patients with moderate-to-severe oral mucositis, and multivariate analysis confirmed it as a significant risk factor.

An analysis of serial buccal mucosa swabs taken throughout the transplantation period showed that, after HCT, Prevotellaceae, Veillonellaceae, and Lactobacillaceae tended to increase in patients without cGVHD. In patients with cGVHD, Staphylococcaceae and Enterobacteriaceae were more likely to be prevalent.

“Mechanistic studies demonstrated that oral pathobionts migrated to the cervical lymph nodes resulting in the persistent activation of activated antigen-presenting cells and the amplification of the allogeneic immune response,” Dr. Reddy and colleagues wrote.

Implications in Clinical Settings

Interventions targeting the oral microbiome during the transplant period, including the application of antibiotic ointment, mitigated cGVHD in a modeling analysis, the study found. Because systemic antibiotic administration is associated with increased GVHD-related mortality in humans, an antibiotic ointment that specifically targets oral microbiota may represent a strategy for controlling local microbiota and 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,” the researchers wrote. “Addressing oral inflammation that leads to dysbiosis could foster immunological tolerance and become a therapeutic target for cGVHD.”